Multidimensional Flow Cytometry for Testing Blood-Handling Medical Devices

Blood handling devices such as left ventricular assist devices and total artificial hearts offer life-saving treatments for patients suffering from severe heart failure. Current devices have clinically proven that heart assist pumps are a safe and effective therapy, and indeed in many cases they are the only available method of treatment. However, current devices cause side effects including stroke, bleeding, infection, and thrombosis, preventing the technology from reaching its full potential. If the side effects could be reduced, then more patients could benefit from these devices. The complications are related to damage to blood cells and proteins as a result of contact with foreign materials and mechanical stress. There is a need for better devices with minimal blood impact to enable more patients to be safely treated; better tools, especially flow cytometry, could support the device development life cycle. In this chapter we review the clinical, in vivo, and in vitro flow cytometry data available for ventricular assist devices, conduct a gap analysis, and identify areas of future possibilities for device developers to establish new flow cytometry-based methodologies

Local chiral potentials and the structure of light nuclei

We present fully local versions of the minimally non-local nucleon-nucleon potentials constructed in a previous paper [M.\ Piarulli {\it et al.}, Phys.\ Rev.\ C {\bf 91}, 024003 (2015)], and use them in hypersperical-harmonics and quantum Monte Carlo calculations of ground and excited states of $^3$H, $^3$He, $^4$He, $^6$He, and $^6$Li nuclei. The long-range part of these local potentials includes one- and two-pion exchange contributions without and with $\Delta$-isobars in the intermediate states up to order $Q^3$ ($Q$ denotes generically the low momentum scale) in the chiral expansion, while the short-range part consists of contact interactions up to order $Q^4$. The low-energy constants multiplying these contact interactions are fitted to the 2013 Granada database in two different ranges of laboratory energies, either 0--125 MeV or 0--200 MeV, and to the deuteron binding energy and $nn$ singlet scattering length. Fits to these data are performed for three models characterized by long- and short-range cutoffs, $R_{\rm L}$ and $R_{\rm S}$ respectively, ranging from $(R_{\rm L},R_{\rm S})=(1.2,0.8)$ fm down to $(0.8,0.6)$ fm. The long-range (short-range) cutoff regularizes the one- and two-pion exchange (contact) part of the potential.Comment: 29 pages, 3 figure

Leukocyte deformation in cardiac assist devices

Ventricular Assist Devices (VADs) are pumps which support failing hearts. While considered by some surgeons as gold standard treatment, current VADs have many complications related to the imposed stress on the blood. In particular, damage to the leukocytes may contribute to infections, currently the biggest post-surgical problem. Our aim was to create a numerical model of a leukocytewhich can be used to investigate leukocyte deformation in VADs. The leukocyte was modelled as a compound liquid droplet and solved in OpenFOAM using the multiphaseInterfoam solver. Initial results are presented for different shear rates, extensional versus planar shear, and for different nucleus sizes

A Conceptual Analysis

Johne’s disease (JD) is a chronic, production-limiting disease of ruminants. Control programs aiming to minimize the effects of the disease on the dairy industry have been launched in many countries, including Canada. Those programs commonly focus on strict hygiene and management improvement, often combined with various testing methods. Concurrently, organic dairy farming has been increasing in popularity. Because organic farming promotes traditional management practices, it has been proposed that organic dairy production regulations might interfere with implementation of JD control strategies. However, it is currently unclear how organic farming would change the risk for JD control. This review presents a brief introduction to organic dairy farming in Canada, JD, and the Canadian JD control programs. Subsequently, organic practices are described and hypotheses of their effects on JD transmission are developed. Empirical research is needed, not only to provide scientific evidence for organic producers, but also for smaller conventional farms employing organic-like management practices

The Inflammatory Response to Ventricular Assist Devices

The therapeutic use of ventricular assist devices (VADs) for end-stage heart failure (HF) patients who are ineligible for transplant has increased steadily in the last decade. In parallel, improvements in VAD design have reduced device size, cost, and device-related complications. These complications include infection and thrombosis which share underpinning contribution from the inflammatory response and remain common risks from VAD implantation. An added and underappreciated difficulty in designing a VAD that supports heart function and aids the repair of damaged myocardium is that different types of HF are accompanied by different inflammatory profiles that can affect the response to the implanted device. Circulating inflammatory markers and changes in leukocyte phenotypes receive much attention as biomarkers for mortality and disease progression. However, they are seldom used to monitor progress during and outcomes from VAD therapy or during the design phase for new devices. Even the partial reversal of heart damage associated with heart failure is a desirable outcome from VAD use. Therefore, improved understanding of the interplay between VADs and the recipient’s inflammatory response would potentially increase their uptake, improve patient lives, and fuel research related to other blood-contacting medical devices. Here we provide a review of what is currently known about inflammation in heart failure and how this inflammatory profile is altered in heart failure patients receiving VAD therapy

Hypothesis and theory : a pathophysiological concept of stroke-induced acute phase response and increased intestinal permeability leading to secondary brain damage

Gut integrity impairment leading to increased intestinal permeability (IP) is hypothesized to be a trigger of critically illness. Approximately 15–20% of human ischemic stroke (IS) victims require intensive care, including patients with impaired level of consciousness or a high risk for developing life-threatening cerebral edema. Local and systemic inflammatory reactions are a major component of the IS pathophysiology and can significantly aggravate brain tissue damage. Intracerebral inflammatory processes following IS have been well studied. Until now, less is known about systemic inflammatory responses and IS consequences apart from a frequently observed post-IS immunosuppression. Here, we provide a hypothesis of a crosstalk between systemic acute phase response (APR), IP and potential secondary brain damage during acute and subacute IS stages supported by preliminary experimental data. Alterations of the acute phase proteins (APPs) C-reactive protein and lipopolysaccharide-binding protein and serum level changes of antibodies directed against Escherichia coli-cell extract antigen (IgA-, IgM-, and IgG-anti-E. coli) were investigated at 1, 2, and 7 days following IS in ten male sheep. We found an increase of both APPs as well as a decrease of all anti-E. coli antibodies within 48 h following IS. This may indicate an early systemic APR and increased IP, and underlines the importance of the increasingly recognized gut-brain axis and of intestinal antigen release for systemic immune responses in acute and subacute stroke stages

Diagnosis and outcome following tenoscopic surgery of the digital flexor tendon sheath in German sports and pleasure horses

Background Digital flexor tendon sheath (DFTS) pathology is an important cause of lameness in horses. The outcome after surgical treatment is variable and depends on the exact diagnosis. Objectives To (1) describe the prevalence of lesions associated with lameness caused by nonseptic DFTS tenosynovitis in a large population of German sports and pleasure horses; (2) determine the sensitivity and specificity of diagnostic imaging techniques for identifying lesions within the DFTS with tenoscopic diagnosis being the gold standard; (3) explore associations between tenoscopically diagnosed lesions and signalment, purpose, and limb affected; and (4) describe the outcome following DFTS tenoscopy with nonseptic DFTS tenosynovitis in this population. Study design Retrospective case series. Methods Medical records of horses admitted for tenoscopic surgery of nonseptic DFTS tenosynovitis between 2011 and 2020 were reviewed. Follow‐up information was obtained via telephone contact. Sensitivity and specificity of ultrasonography and contrast tenography were determined using tenoscopic diagnosis as gold standard and univariable analysis was used to explore associations between signalment, case history, and tenoscopic diagnosis. Results Medical records from 131 horses were retrieved, of which 8 horses had bilateral disease and 6 horses were presented for tenoscopy on two separate occasions (3 for tenoscopy in the same limb, 3 in a different limb), thus, making a total of 145 limbs. Lesions were most commonly diagnosed in the deep (DDFT; n = 55 limbs) and superficial (SDFT; n = 55 limbs) digital flexor tendons. Manica flexoria (MF) lesions were detected in 44 limbs and palmar/plantar annular ligament (PAL) constriction in 99 limbs. In 36 limbs, only one structure within the DFTS was injured, whereas in 109 limbs a combination of lesions was noted, the most common being the combination of a SDFT lesion with PAL constriction. All affected limbs were examined with diagnostic ultrasonography; contrast tenography was performed in 86 limbs. For diagnosis of MF and DDFT tears, tenography was more sensitive (89% [confidence interval, CI: 65.4%–95.2%]; 72% [CI: 46.4%–89.3%], respectively) than specific (64% [CI: 52.5%–77.6%]; 53% [CI: 42.2%–73.3%], respectively) whereas ultrasonography was more specific (92% [CI: 84.5%–96.3%]; 92% [CI: 83.6%–96.0%]) with lower sensitivity (64% [CI: 47.7%–77.2%]; 54% [CI: 39.5%–67.9%]). For SDFT lesions, ultrasonography was highly specific (94% [CI: 86.9%–97.9%]) with lower sensitivity (66% [CI: 51.3%–77.4%]). Follow‐up information following first surgery was obtained for 118 horses (132 limbs): 18 (15.3%) of 118 horses remained chronically lame, 40 (33.8%) performed at a reduced level and 60 (50.8%) performed at the same or higher level following rehabilitation after tenoscopy. Horses with DDFT lesions had the poorest outcomes with only 36.6% returning to the same or higher level of exercise. Main limitations Retrospective analysis of clinical records and subjective outcome assessment based on owner follow‐up with potential recall bias. Findings on diagnostic imaging are impacted by many factors including equipment quality and operator expertise and experience. Conclusion Diagnostic imaging techniques were complimentary and contrast tenography was sensitive and ultrasonography was specific for the diagnosis of MF and DDFT lesions. Following tenoscopic surgery for nonseptic tenosynovitis of the DFTS, approximately half the cases were able to return to preinjury level of exercise

Seasonal Prediction of Arabian Sea Marine Heatwaves

Marine heatwaves are known to have a detrimental impact on marine ecosystems, yet predicting when and where they will occur remains a challenge. Here, using a large ensemble of initialized predictions from an Earth System Model, we demonstrate skill in predictions of summer marine heatwaves over large marine ecosystems in the Arabian Sea seven months ahead. Retrospective forecasts of summer (June to August) marine heatwaves initialized in the preceding winter (November) outperform predictions based on observed frequencies. These predictions benefit from initialization during winters of medium to strong El Niño conditions, which have an impact on marine heatwave characteristics in the Arabian Sea. Our probabilistic predictions target spatial characteristics of marine heatwaves that are specifically useful for fisheries management, as we demonstrate using an example of Indian oil sardine (Sardinella longiceps)