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Single ventricle heart defects (SVDs) are congenital disorders that result in a variety of complications, including increased ventricular mechanical strain and mixing of oxygenated and deoxygenated blood, leading to heart failure without surgical intervention. Corrective surgery for SVDs are traditionally handled by the Fontan procedure, requiring a vascular conduit for completion. Although effective, current conduits are limited by their inability to aid in pumping blood into the pulmonary circulation. In this report, we propose an innovative and versatile design strategy for a tissue engineered pulsatile conduit (TEPC) to aid circulation through the pulmonary system by producing contractile force. Several design strategies were tested for production of a functional TEPC. Ultimately, we found that porcine extracellular matrix (ECM)-based engineered heart tissue (EHT) composed of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and primary cardiac fibroblasts (HCF) wrapped around decellularized human umbilical artery (HUA) made an efficacious basal TEPC. Importantly, the TEPCs showed effective electrical and mechanical function. Initial pressure readings from our TEPC in vitro (0.68 mmHg) displayed efficient electrical conductivity enabling them to follow electrical pacing up to a 2 Hz frequency. This work represents a proof of principle study for our current TEPC design strategy. Refinement and optimization of this promising TEPC design will lay the groundwork for testing the construct's therapeutic potential in the future. Together this work represents a progressive step toward developing an improved treatment for SVD patients. Single Ventricle Cardiac defects (SVD) are a form of congenital disorder with a morbid prognosis without surgical intervention. These patients are treated through the Fontan procedure which requires vascular conduits to complete. Fontan conduits have been traditionally made from stable or biodegradable materials with no pumping activity. Here, we propose a tissue engineered pulsatile conduit (TEPC) for use in Fontan circulation to alleviate excess strain in SVD patients. In contrast to previous strategies for making a pulsatile Fontan conduit, we employ a modular design strategy that allows for the optimization of each component individually to make a standalone tissue. This work sets the foundation for an in vitro , trainable human induced pluripotent stem cell based TEPC. Image, graphical abstract [ABSTRACT FROM AUTHOR]

• Miniature Tissue Equivalent Proportional Counters can work without gas-flow. • The new sealed mini-TEPC gives reproducible results over a period of 4 months. • The new mini-TEPC can be used as a precise LET-monitor in proton therapy. • The new mini-TEPC measurements result in a reasonable RBE-assessment. • The mini-TEPC can be used for a comparative study of different radiotherapy centres. A new mini-TEPC with cylindrical sensitive volume of 0.9 mm in diameter and height, and with external diameter of 2.7 mm, has been developed to work without gas flow. With such a mini counter we have measured the physical quality of the 62 MeV therapeutic proton beam of CATANA (Catania, Italy). Measurements were performed at six precise positions along the Spread-Out Bragg Peak (SOBP): 1.4, 19.4, 24.6, 29.0, 29.7 and 30.8 mm, corresponding to positions of clinical relevance (entrance, proximal, central, and distal-edge of the SOBP) or of high lineal energy transfer (LET) increment (distal-dose drop off). Without refilling the microdosimeter with new gas, the measurements were repeated at the same positions 4 months later, in order to study the stability of the response in sealed-mode operation. From the microdosimetric spectra the frequency-mean lineal energy y - F and the dose-mean lineal energy y - D were derived and compared with average LET values calculated by means of Geant4 simulations. The comparison points out, in particular, a good agreement between microdosimetric y - D and the total dose-average L E T ¯ d , which is the average LET of the mixed radiation field, including the contribution by nuclear reactions. [ABSTRACT FROM AUTHOR]

Purpose To measure the environmental doses from stray neutrons in the vicinity of a solid slab phantom as a function of beam energy, field size and modulation width, using the proton pencil beam scanning (PBS) technique. Method Measurements were carried out using two extended range WENDI-II rem-counters and three tissue equivalent proportional counters. Detectors were suitably placed at different distances around the RW3 slab phantom. Beam irradiation parameters were varied to cover the clinical ranges of proton beam energies (100–220 MeV), field sizes ((2 × 2)–(20 × 20) cm 2 ) and modulation widths (0–15 cm). Results For pristine proton peak irradiations, large variations of neutron H ∗ (10)/ D were observed with changes in beam energy and field size, while these were less dependent on modulation widths. H ∗ (10)/ D for pristine proton pencil beams varied between 0.04 μSv Gy −1 at beam energy 100 MeV and a (2 × 2) cm 2 field at 2.25 m distance and 90° angle with respect to the beam axis, and 72.3 μSv Gy −1 at beam energy 200 MeV and a (20 × 20) cm 2 field at 1 m distance along the beam axis. Conclusions The obtained results will be useful in benchmarking Monte Carlo calculations of proton radiotherapy in PBS mode and in estimating the exposure to stray radiation of the patient. Such estimates may be facilitated by the obtained best-fitted simple analytical formulae relating the stray neutron doses at points of interest with beam irradiation parameters. [ABSTRACT FROM AUTHOR]