Two dimensional soliton in tumor induced angiogenesis

Ensemble averages of a stochastic model show that, after a formation stage, the tips of active blood vessels in an angiogenic network form a moving two dimensional stable diffusive soliton, which advances toward sources of growth factor. Here we use methods of multiple scales to find the diffusive soliton as a solution of a deterministic equation for the mean density of active endothelial cells tips. We characterize the diffusive soliton shape in a general geometry, and find that its vector velocity and the trajectory of its center of mass along curvilinear coordinates solve appropriate collective coordinate equations. The vessel tip density predicted by the soliton compares well with that obtained by ensemble averages of simulations of the stochastic model.Comment: 35 pages, 10 figures, to appear in JSTA

Soliton approximation in continuum models of leader-follower behavior

Complex biological processes involve collective behavior of entities (bacteria, cells, animals) over many length and time scales and can be described by discrete models that track individuals or by continuum models involving densities and fields. We consider hybrid stochastic agent-based models of branching morphogenesis and angiogenesis (new blood vessel creation from pre-existing vasculature), which treat cells as individuals that are guided by underlying continuous chemical and/or mechanical fields. In these descriptions, leader (tip) cells emerge from existing branches and follower (stalk) cells build the new sprout in their wake. Vessel branching and fusion (anastomosis) occur as a result of tip and stalk cell dynamics. Coarse-graining these hybrid models in appropriate limits produces continuum partial differential equations (PDEs) for endothelial cell densities that are more analytically tractable. While these models differ in nonlinearity, they produce similar equations at leading order when chemotaxis is dominant. We analyze this leading order system in a simple quasi-one-dimensional geometry and show that the numerical solution of the leading order PDE is well described by a soliton wave that evolves from vessel to source. This wave is an attractor for intermediate times until it arrives at the hypoxic region releasing the growth factor. The mathematical techniques used here thus identify common features of discrete and continuum approaches and provide insight into general biological mechanisms governing their collective dynamics.Comment: 13 pages, 9 figure

Assessment of vascular perfusion kinetics using contrast-enhanced ultrasound for the diagnosis of prostatic disease in dogs

Vascular perfusion was assessed in 10 dogs without prostatic abnormalities and 26 dogs with prostatic disease using contrast-enhanced ultrasound. The time to reach peak contrast intensity (TTP) and peak perfusion intensity (PPI) were measured, and histological biopsies were collected from each dog. Biopsies confirmed normal prostate (n = 10), benign prostatic hyperplasia (n = 11), mixed benign pathology (n = 9), prostatitis (n = 1), prostatic malignancy [adenocar- cinoma (n = 4); leiomyosarcoma (n = 1)]. In normal dogs, mean PPI was 16.8% ± 5.8 SD, and mean TTP was 33.6 ± 6.4 s. Benign conditions overall were not statistically different from normal dogs (p > 0.05); for benign prostatic hyperplasia, mean PPI was 16.9 ± 3.8%, and mean TTP was 26.2 ± 5.8 s; for mixed benign pathology mean PPI was 14.8 ± 7.8%, and mean TTP was 31.9 ± 9.7 s; for prostatitis, PPI was 14.2%, and TTP was 25.9 s. The malignant conditions overall had perfusion values that differed from the normal dogs (p < 0.05), although evaluation of the data for individ- ual malignancies did not demonstrate a consistent trend; for adenocarcinomas, the PPI was numerically higher with a mean of 23.7 ± 1.9%, and the mean TTP was 26.9 ± 4.8 s, whilst for the dog with leiomyosarcoma values were numerically lower with a PPI of 14.1% and TTP of 41.3 s. Contrast- enhanced ultrasound appears to offer some ability to docu- ment differences in perfusion that may differentiate between malignant and benign lesions, although studies with larger numbers of animals are required to confirm this contention

Lymphatic drainage mapping with indirect lymphography for canine mammary tumors

Mammary gland tumors are the most common canine neoplasms. They account for 25– 50% of all tumors diagnosed in bitches. Metastases and recurrences develop in about 35–70% of bitches following excision. The presence of regional lymph node metastases is a relevant factor affecting prognosis and treatment in cases of mammary gland tumors. The sentinel lymph node (SLN) is the first lymph node (or nodes) in the regional lymphatic basin that receives lymphatic flow from the primary neoplasm. The aim of this study is to investigate the SLN with indirect lymphography for a mammary tumor in dogs. The knowledge of the precise drainage pattern and SLN of the neoplastic mammary glands would provide clinically relevant information to the surgeon and to the oncologist, and it would be of high importance for the surgeon not only for performing the most adequate surgical excision but also for determining an accurate post-surgical prognosis

Extracorporeal CO 2 Removal During Renal Replacement Therapy to Allow Lung-Protective Ventilation in Patients With COVID-19-Associated Acute Respiratory Distress Syndrome

The aim of this retrospective multicenter observational study is to test the feasibility and safety of a combined extracorporeal CO 2 removal (ECCO 2 R) plus renal replacement therapy (RRT) system to use an ultraprotective ventilator setting while maintaining (1) an effective support of renal function and (2) values of pH within the physiologic limits in a cohort of coronavirus infectious disease 2019 (COVID-19) patients. Among COVID-19 patients admitted to the intensive care unit of 9 participating hospitals, 27 patients with acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) requiring invasive mechanical ventilation undergoing ECCO 2 R-plus-RRT treatment were included in the analysis. The treatment allowed to reduce V T from 6.0 ± 0.6 mL/kg at baseline to 4.8 ± 0.8, 4.6 ± 1.0, and 4.3 ± 0.3 mL/kg, driving pressure (ΔP) from 19.8 ± 2.5 cm H 2 O to 14.8 ± 3.6, 14.38 ± 4.1 and 10.2 ± 1.6 cm H 2 O after 24 hours, 48 hours, and at discontinuation of ECCO 2 R-plus-RRT (T3), respectively ( p &lt; 0.001). PaCO 2 and pH remained stable. Plasma creatinine decreased over the study period from 3.30 ± 1.27 to 1.90 ± 1.30 and 1.27 ± 0.90 mg/dL after 24 and 48 hours of treatment, respectively ( p &lt; 0.01). No patient-related events associated with the extracorporeal system were reported. These data show that in patients with COVID-19-induced ARDS and AKI, ECCO 2 R-plus-RRT is effective in allowing ultraprotective ventilator settings while maintaining an effective support of renal function and values of pH within physiologic limits

Developing a systems-based framework of the factors influencing dietary and physical activity behaviours in ethnic minority populations living in Europe - a DEDIPAC study

Background: Some ethnic minority populations have a higher risk of non-communicable diseases than the majority European population. Diet and physical activity behaviours contribute to this risk, shaped by a system of inter-related factors. This study mapped a systems-based framework of the factors influencing dietary and physical activity behaviours in ethnic minority populations living in Europe, to inform research prioritisation and intervention development. Methods: A concept mapping approach guided by systems thinking was used: i. Preparation (protocol and terminology); ii. Generating a list of factors influencing dietary and physical activity behaviours in ethnic minority populations living in Europe from evidence (systematic mapping reviews) and ‘eminence’ (89 participants from 24 academic disciplines via brainstorming, an international symposium and expert review) and; iii. Seeking consensus on structuring, rating and clustering factors, based on how they relate to each other; and iv. Interpreting/utilising the framework for research and interventions. Similar steps were undertaken for frameworks developed for the majority European population. Results: Seven distinct clusters emerged for dietary behaviour (containing 85 factors) and 8 for physical activity behaviours (containing 183 factors). Four clusters were similar across behaviours: Social and cultural environment; Social and material resources; Psychosocial; and Migration context. Similar clusters of factors emerged in the frameworks for diet and physical activity behaviours of the majority European population, except for ‘migration context’. The importance of factors across all clusters was acknowledged, but their relative importance differed for ethnic minority populations compared with the majority population. Conclusions: This systems-based framework integrates evidence from both expert opinion and published literature, to map the factors influencing dietary and physical activity behaviours in ethnic minority groups. Our findings illustrate that innovative research and complex interventions need to be developed that are sensitive to the needs of ethnic minority populations. A systems approach that encompasses the complexity of the inter-related factors that drive behaviours may inform a more holistic public health paradigm to more effectively reach ethnic minorities living in Europe, as well as the majority host population