Dynamic Assessment of Cardiovascular Biomarkers

The behaviour of cardiovascular parameters during exercise remains unsettled. Arterial stiffness is one of the most promising and innovative vascular biomarkers; this vessel property is usually evaluated at rest, but, since it aims to describe a stress-strain vessel behaviour, it is not a static parameter. Hence, our aim was to develop a method able to evaluate carotid elasticity dynamically in order to investigate if this analysis can provide information regarding differences between populations (i.e. patients and healthy subjects). We developed an approach based on a contour tracking algorithm applied to ultrasound B-mode image sequences and used it in conjunction with a local pressure estimation to assess carotid distensibility. The method's reproducibility was evaluated by analyzing a group of healthy volunteers during two sessions 3 days apart. Repeatability was expressed as coefficient of variation and satisfactory results were obtained in exercise. After testing the robustness of the technique, the approach was applied during graded bicycle semi-supine exercise session in patients with known or suspected coronary artery disease (CAD) and results were compared with a control group. 36 consecutive patients (20 men, 61±8years), and 18 healthy volunteers (9 men, 34±3 years) were recruited. Right carotid diameter (D) and distension (ΔD) were estimated by the developed ultrasound B-mode image processing method, and central pulse pressure (PPa) by radial tonometry; then, carotid elasticity was expressed as cross-sectional distensibility coefficient (DC). Besides the vascular evaluation we introduced the estimation of left-ventricular elastance (ElvI) by echocardiography, in order to obtain a more integrated dynamic picture including arterial-ventricular coupling. All measurements were performed at rest, peak of age-dependent maximal heart rate and during recovery. At rest, D and PPa were higher in patients than in controls, whereas no significant differences were observed in ΔD and mean blood pressure; DC and ElvI were lower in patients than in healthy volunteers. At peak mean blood pressure increased both in patients and controls; DC significantly decreased and D increased in healthy subjects but not in patients. Finally ElvI highly increased in controls but not in patients. Behaviours of the two populations during recovery were similar. Hence, we can conclude that the developed approach provides a suitable reproducibility for clinical studies and was able to dynamically discriminate between different kind of subjects. In particular, in patients with known or suspected CAD, carotid distensibility, which at rest is lower than in healthy controls, remains unchanged during maximal exercise, despite a similar increase in mean blood pressure in the two populations. This difference is underlined also by the absence of strong cardiac response and carotid vasodilation in the pathologic population. From our preliminary results, the importance of a dynamic assessment of carotid elasticity was confirmed, and there is evidence of a clinical need including a simple and robust device to more easily perform this kind of analysis than by ultrasound. In our lab a first prototype based on vibration approach was designed and might be the suitable solution for implementing low-cost and easy carotid elasticity dynamic evaluation. In the future, the cardiologist ambulatory might provide, besides cardiac and pressure monitoring, additive relevant clinical information from an arterial elasticity 24-hours device

Impact of the PDFs on the Z and W lineshapes at LHC

The parton distribution functions (PDFs) of the proton play a role in determining the lineshape of $Z$ and $W$ bosons produced at the LHC. In particular, the mode of the gauge boson virtuality is shifted with respect to the pole due to the dependence of the partonic luminosity on the boson virtuality. The knowledge of this shift contributes to the systematic uncertainty for a direct measurement of the boson mass. A detailed study of the shift and of its systematic uncertainty due to the limited knowledge of the PDFs is obtained using a tree-level model of $Z$ and $W$ boson production in proton-proton collisions at $\sqrt{s}=13$ TeV. A Monte Carlo simulation is further used to validate the tree-level model and study the dependence of the shift on the transverse momentum of the gauge bosons. The tree-level calculation is found to provide a good description of the shift. The systematic uncertainty on the lineshape due to the PDFs is estimated to be below one MeV in the phase-space relevant for a future high-precision mass measurement of the gauge boson masses at the LHC

The Ultrasound Window Into Vascular Ageing: A Technology Review by the VascAgeNet COST Action

Arteriosclerosis; Ultrasound; Vascular ageingArteriosclerosi; Ecografia; Envelliment vascularArteriosclerosis; Ecografía; Envejecimiento vascularNon-invasive ultrasound (US) imaging enables the assessment of the properties of superficial blood vessels. Various modes can be used for vascular characteristics analysis, ranging from radiofrequency (RF) data, Doppler- and standard B/M-mode imaging, to more recent ultra-high frequency and ultrafast techniques. The aim of the present work was to provide an overview of the current state-of-the-art non-invasive US technologies and corresponding vascular ageing characteristics from a technological perspective. Following an introduction about the basic concepts of the US technique, the characteristics considered in this review are clustered into: 1) vessel wall structure; 2) dynamic elastic properties, and 3) reactive vessel properties. The overview shows that ultrasound is a versatile, non-invasive, and safe imaging technique that can be adopted for obtaining information about function, structure, and reactivity in superficial arteries. The most suitable setting for a specific application must be selected according to spatial and temporal resolution requirements. The usefulness of standardization in the validation process and performance metric adoption emerges. Computer-based techniques should always be preferred to manual measures, as long as the algorithms and learning procedures are transparent and well described, and the performance leads to better results. Identification of a minimal clinically important difference is a crucial point for drawing conclusions regarding robustness of the techniques and for the translation into practice of any biomarker.This article is based upon work from COST Action CA18216 VascAgeNet, supported by COST (European Cooperation in Science and Technology, www.cost.eu). A.G. has received funding from “La Caixa” Foundation (LCF/BQ/PR22/11920008). R.E.C is supported by the National Health and Medical Research Council of Australia (reference: 2009005) and by a National Heart Foundation Future Leader Fellowship (reference: 105636). J.A. acknowledges support from the British Heart Foundation [PG/15/104/31913], the Wellcome EPSRC Centre for Medical Engineering at King's College London [WT 203148/Z/16/Z], and the Cardiovascular MedTech Co-operative at Guy's and St Thomas' NHS Foundation Trust [MIC-2016-019]

Isolation of an "early" transit amplifying keratinocyte population in human epidermis: a role for the low affinity neurotrophin receptor CD271

In the interfollicular epidermis (IFE), stem cells (KSC) generate transit amplifying (TA) cells that, after symmetric divisions, produce differentiating daughters. Here, we isolated and characterized the highly proliferative interfollicular epidermal basal cell population "early" TA (ETA) cells, based on their capacity to adhere to type IV collagen. Proliferation and colony-forming efficiency in ETA cells are lower than in KSC but higher than in "late" TA (LTA). Stemness, proliferation, and differentiation markers confirmed that ETA cells display a unique phenotype. Skin reconstructs derived from ETA cells present different features (epidermal thickness, Ki67, and Survivin expression), as compared to skin equivalents generated from either KSC or LTA cells. The low-affinity neurotrophin receptor CD271, which regulates the KSC to TA cell transition in the human epidermis through an on/off switch control mechanism, is predominantly expressed in ETA cells. Skin equivalents generated from siRNA CD271 ETA cells display a more proliferative and less differentiated phenotype, as compared to mock-derived reconstructs. Consistently, CD271 overexpression in LTA cells generates a more proliferative skin equivalent than mock LTA cells. Finally, the CD271 level declines with cellular senescence, while it induces a delay in p16INK4 expression. We conclude that ETA cells represent the first KSC progenitor with exclusive features. CD271 identifies and modulates ETA cells, thus participating in the early differentiation and regenerative capacity of the human epidermis

JLB: a flexible and effective device in critical patients. Review of clinical cases

JLB catheter (Deltamed Inc) is an alternative way to manage difficult venous access; it is placed under US-guidance in large bore veins, with an easy-sterile approach. Internal jugular vein (IJV) is the first choice for cannulation, followed by subclavian or deep upper-arm veins. The catheter is available in different lengths and gauges, it allows high flow rates and can be left in place up to 30 days. From June 2015 to March 2017, JLB has been positioned in 409 patients: in 354 as primary access in IJV, brachial or subclavian vein; in 55 cases JLB became an introducing line for the Seldinger guidewire and further CVC positioning. All clinical cases were reviewed selecting those with greater clinical relevance. We report 8 cases in which JLB resulted determinant for the patient treatment: a 16 years old obese girl born with perinatal distress, a 78 years old obese woman with hemorrhagic shock caused by gastrointestinal bleeding, a 40 years old man with severe hypokalemia, a 30 years old man with severe sepsis, a 40 years old man with Becker’s muscular dystrophy and severe sepsis, a 40 years old man with multiple myeloma who had to carry out cycles of chemotherapy, a 76 years old man with CMV pancolitis and myelofibrosis who needed parenteral nutrition, antiviral therapy and frequent blood and platelets transfusion. Moreover, it has been useful in elderly patients who needed to carry out palliative care for seniority or cancer lasting up to 30 days . In our experience the JLB catheter is safe, easy to place, quick and cost –effective. It is a valid solution either in unstable patients requiring an immediate access in emergency and stable patients with difficult venous access, in which invasive devices can be considered an over-treatment

Carotid Ultrasound Boundary Study (CUBS): An Open Multicenter Analysis of Computerized Intima–Media Thickness Measurement Systems and Their Clinical Impact

[Abstract] Common carotid intima–media thickness (CIMT) is a commonly used marker for atherosclerosis and is often computed in carotid ultrasound images. An analysis of different computerized techniques for CIMT measurement and their clinical impacts on the same patient data set is lacking. Here we compared and assessed five computerized CIMT algorithms against three expert analysts’ manual measurements on a data set of 1088 patients from two centers. Inter- and intra-observer variability was assessed, and the computerized CIMT values were compared with those manually obtained. The CIMT measurements were used to assess the correlation with clinical parameters, cardiovascular event prediction through a generalized linear model and the Kaplan–Meier hazard ratio. CIMT measurements obtained with a skilled analyst's segmentation and the computerized segmentation were comparable in statistical analyses, suggesting they can be used interchangeably for CIMT quantification and clinical outcome investigation. To facilitate future studies, the entire data set used is made publicly available for the community at http://dx.doi.org/10.17632/fpv535fss7.