Automata, reason, and free will: Leibniz's critique of Descartes on animal and human nature.

This paper argues that Leibniz's use of the concept of "automaton" to characterize the nature of souls and bodies of living beings constitutes a systematic critique of Descartes' earlier use of automata. Whereas Descartes conceived non-human animals in terms of mechanical automata, he also denied that the human rational soul can be modeled on the nature of an automaton. In contrast, Leibniz understood living things to involve both an organic body, or "natural automaton," as well as an immaterial soul, or "spiritual automaton," that spontaneously produces its own perceptions. In extending the concept of the automaton to souls, Leibniz rejected key Cartesian assumptions about animals and free will and draws on the concept of the automaton to understand a range of cognitive capacities including volition. Leibniz thus occupies a distinctive place in the history of the use of automata to understand the nature of living things.

Implementation outcomes of national decentralization of integrated outpatient services for severe non-communicable diseases to district hospitals in Rwanda.

OBJECTIVES: Effective coverage of non-communicable disease (NCD) care in sub-Saharan Africa remains low, with the majority of services still largely restricted to central referral centres. Between 2015 and 2017, the Rwandan Ministry of Health implemented a strategy to decentralise outpatient care for severe chronic NCDs, including type 1 diabetes, heart failure and severe hypertension, to rural first-level hospitals. This study describes the facility-level implementation outcomes of this strategy. METHODS: In 2014, the Ministry of Health trained two nurses in each of the country's 42 first-level hospitals to implement and deliver nurse-led, integrated, outpatient NCD clinics, which focused on severe NCDs. Post-intervention evaluation occurred via repeated cross-sectional surveys, informal interviews and routinely collected clinical data over two rounds of visits in 2015 and 2017. Implementation outcomes included fidelity, feasibility and penetration. RESULTS: By 2017, all NCD clinics were staffed by at least one NCD-trained nurse. Among the approximately 27 000 nationally enrolled patients, hypertension was the most common diagnosis (70%), followed by type 2 diabetes (19%), chronic respiratory disease (5%), type 1 diabetes (4%) and heart failure (2%). With the exception of warfarin and beta-blockers, national essential medicines were available at more than 70% of facilities. Clinicians adhered to clinical protocols at approximately 70% agreement with evaluators. CONCLUSION: The government of Rwanda was able to scale a nurse-led outpatient NCD programme to all first-level hospitals with good fidelity, feasibility and penetration as to expand access to care for severe NCDs.

In Silico Performance of a Recellularized Tissue-Engineered Transcatheter Aortic Valve.

Commercially available heart valves have many limitations, such as a lack of remodeling, risk of calcification, and thromboembolic problems. Many state-of-the-art tissue-engineered heart valves (TEHV) rely on recellularization to allow remodeling and transition to mechanical behavior of native tissues. Current in vitro testing is insufficient in characterizing a soon-to-be living valve due to this change in mechanical response; thus, it is imperative to understand the performance of an in situ valve. However, due to the complex in vivo environment, this is difficult to accomplish. Finite element (FE) analysis has become a standard tool for modeling mechanical behavior of heart valves; yet, research to date has mostly focused on commercial valves. The purpose of this study has been to evaluate the mechanical behavior of a TEHV material before and after 6 months of implantation in a rat subdermis model. This model allows the recellularization and remodeling potential of the material to be assessed via a simple and inexpensive means prior to more complex ovine orthotropic studies. Biaxial testing was utilized to evaluate the mechanical properties, and subsequently, constitutive model parameters were fit to the data to allow mechanical performance to be evaluated via FE analysis of a full cardiac cycle. Maximum principal stresses and strains from the leaflets and commissures were then analyzed. The results of this study demonstrate that the explanted tissues had reduced mechanical strength compared to the implants but were similar to the native tissues. For the FE models, this trend was continued with similar mechanical behavior in explant and native tissue groups and less compliant behavior in implant tissues. Histology demonstrated recellularization and remodeling although remodeled collagen had no clear directionality. In conclusion, we observed successful recellularization and remodeling of the tissue giving confidence to our TEHV material; however, the mechanical response indicates the additional remodeling would likely occur in the aortic/pulmonary position.

Selective Coordination of Gallium(III), Zinc(II), and Copper(II) by an Asymmetric Dinucleating Ligand: A Model for Metallophosphatases.

Complexation studies of the dinucleating ligand H3 L (H3 L=2-{[bis(pyridin-2-ylmethyl)amino]methyl}-6-{[bis(6-pivaloylamidopyridin-2-ylmethyl)amino]methyl}-4-methylphenol), with metal-binding sites A and B, which both provide four donors to a metal ion; a tertiary amine; two pyridines (substituted with amide hydrogen-bond donors in site B), and a bridging phenolate, with Zn(II) , Cu(II) , and Ga(III) are reported. The titration of H3 L with the three metal ions in solution was monitored by NMR spectroscopy or EPR and UV/Vis/near-IR spectroscopy, as well as by ESI-MS to analyze the selectivity of the two metal-ion sites A and B of this model ligand for metallophosphatases; the spectroscopic assignments are supported by X-ray crystallography results. The first Zn(II) ion coordinates to site A with unsubstituted pyridine donors and, upon addition of a second equivalent of Zn(II) , this coordinates to the sterically less accessible site B. From a similar titration with Ga(III) , it emerges that only a mononuclear complex is obtained, with the Ga(III) center coordinated to site A. When one equivalent of Ga(III) is reacted with the mononuclear Zn(II) complex, Zn(II) is forced by Ga(III) to exchange the site; this results in a dinuclear complex with Ga(III) in site A and Zn(II) in site B. With Cu(II) , two isomers are observed: one with and the other without a bridging phenolate; these differ significantly in their spectroscopic and magnetic properties.

An Approach to More Accurate Model Systems for Purple Acid Phosphatases (PAPs).

The active site of mammalian purple acid phosphatases (PAPs) have a dinuclear iron site in two accessible oxidation states (Fe(III)2 and Fe(III)Fe(II)), and the heterovalent is the active form, involved in the regulation of phosphate and phosphorylated metabolite levels in a wide range of organisms. Therefore, two sites with different coordination geometries to stabilize the heterovalent active form and, in addition, with hydrogen bond donors to enable the fixation of the substrate and release of the product, are believed to be required for catalytically competent model systems. Two ligands and their dinuclear iron complexes have been studied in detail. The solid-state structures and properties, studied by X-ray crystallography, magnetism, and Mössbauer spectroscopy, and the solution structural and electronic properties, investigated by mass spectrometry, electronic, nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and Mössbauer spectroscopies and electrochemistry, are discussed in detail in order to understand the structures and relative stabilities in solution. In particular, with one of the ligands, a heterovalent Fe(III)Fe(II) species has been produced by chemical oxidation of the Fe(II)2 precursor. The phosphatase reactivities of the complexes, in particular, also of the heterovalent complex, are reported. These studies include pH-dependent as well as substrate concentration dependent studies, leading to pH profiles, catalytic efficiencies and turnover numbers, and indicate that the heterovalent diiron complex discussed here is an accurate PAP model system.

The effect of long-term corticosterone treatment on blood cell differentials and function in laboratory and wild-caught amphibian models.

The effect of long-term stress on amphibian immunity is not well understood. We modeled a long-term endocrine stress scenario by elevating plasma corticosterone in two species of amphibians and examined effects on white blood cell differentials and innate immune activity. Plasma corticosterone was elevated in American bullfrogs (Lithobates catesbeianus) by surgically implanting corticosterone capsules and in African clawed frogs (Xenopus laevis) by immersion in corticosterone-treated water. To provide a context for our results within endogenous corticosterone fluctuations, diurnal plasma corticosterone cycles were determined. A daily low of corticosterone was observed in X. laevis at 12:00, while a significant pattern was not observed in L. catesbeianus. Elevated plasma corticosterone levels increased the ratio of peripheral neutrophils to lymphocytes, in both species, and decreased eosinophil concentrations in L. catesbeianus over a long-term period. Whole blood oxidative burst generally correlated with neutrophil concentrations, and thus was increased with corticosterone treatment, significantly in L. catesbeianus. In L. catesbeianus, an endogenous response of eosinophils and lymphocytes to implanted empty (sham) capsules was observed, but this effect was attenuated by corticosterone. Peripheral monocyte and basophil concentrations were not significantly altered by corticosterone treatment in either species. Our results show that long-term stress can alter amphibian immune parameters for extended periods and may play a role in susceptibility to disease.

Insights into the electronic structure of Cu(II) bound to an imidazole analogue of westiellamide.

Three synthetic analogues of westiallamide, H3L(wa), have previously been synthesized (H3L(1-3)) that have a common backbone (derived from l-valine) with H3L(wa) but differ in their heterocyclic rings (imidazole, oxazole, thiazole, and oxazoline). Herein we explore in detail through high-resolution pulsed electron paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) spectroscopy in conjunction with density functional theory (DFT) the geometric and electronic structures of the mono- and dinuclear Cu(II) complexes of these cyclic pseudo hexapeptides. Orientation-selective hyperfine sublevel correlation, electron nuclear double resonance, and three-pulse electron spin echo envelope modulation spectroscopy of [Cu(II)(H2L(1))(MeOH)2](+) reveal delocalization of the unpaired electron spin onto the ligating and distal nitrogens of the coordinated heterocyclic rings and that they are magnetically inequivalent. DFT calculations confirm this and show similar spin densities on the distal heteroatoms in the heterocyclic rings coordinated to the Cu(II) ion in the other cyclic pseudo hexapeptide [Cu(II)(H2L(2,3,wa))(MeOH)2](+) complexes. The magnetic inequivalencies in [Cu(II)(H2L(1))(MeOH)2](+) arise from different orientations of the heterocyclic rings coordinated to the Cu(II) ion, and the delocalization of the unpaired electron onto the distal heteroatoms within these N-methylimidazole rings depends upon their location with respect to the Cu(II) d(x(2)-y(2)) orbital. A systematic study of DFT functionals and basis sets was undertaken to examine the ability to reproduce the experimentally determined spin Hamiltonian parameters. Inclusion of spin-orbit coupling (SOC) using MAG-ReSpect or ORCA with a BHLYP/IGLO-II Wachters setup with SOC corrections and ∼38% Hartree-Fock exchange gave the best predictions of the g and A((63)Cu) matrices. DFT calculations of the (14)N hyperfine and quadrupole parameters for the distal nitrogens of the coordinated heterocyclic rings in [Cu(II)(H2L(1))(MeOH)2](+) with the B1LYP functional and the SVP basis set were in excellent agreement with the experimental data, though other choices of functional and basis set also provided reasonable values. MCD, EPR, mass spectrometry, and DFT showed that preparation of the dinuclear Cu(II) complex in a 1:1 MeOH/glycerol mixture (necessary for MCD) resulted in the exchange of the bridging methoxide ligand for glycerol with a corresponding decrease in the magnitude of the exchange coupling.

Electronic structure of the oxygen evolving complex in photosystem II, as revealed by 55Mn Davies ENDOR studies at 2.5 K.

We report the first (55)Mn pulsed ENDOR studies on the S2 state multiline spin ½ centre of the oxygen evolving complex (OEC) in Photosystem II (PS II), at temperatures below 4.2 K. These were performed on highly active samples of spinach PS II core complexes, developed previously in our laboratories for photosystem spectroscopic use, at temperatures down to 2.5 K. Under these conditions, relaxation effects which have previously hindered observation of most of the manganese ENDOR resonances from the OEC coupled Mn cluster are suppressed. (55)Mn ENDOR hyperfine couplings ranging from ∼50 to ∼680 MHz are now seen on the S2 state multiline EPR signal. These, together with complementary high resolution X-band CW EPR measurements and detailed simulations, reveal that at least two and probably three Mn hyperfine couplings with large anisotropy are seen, indicating that three Mn(III) ions are likely present in the functional S2 state of the enzyme. This suggests a low oxidation state paradigm for the OEC (mean Mn oxidation level 3.0 in the S1 state) and unexpected Mn exchange coupling in the S2 state, with two Mn ions nearly magnetically silent. Our results rationalize a number of previous ligand ESEEM/ENDOR studies and labelled water exchange experiments on the S2 state of the photosystem, in a common picture which is closely consistent with recent photo-assembly (Kolling et al., Biophys. J. 2012, 103, 313-322) and large scale computational studies on the OEC (Gatt et al., Angew. Chem., Int. Ed. 2012, 51, 12025-12028, Kurashige et al. Nat. Chem. 2013, 5, 660-666).

Effect of mechanical fatigue on commercial bioprosthetic TAVR valve mechanical and microstructural properties.

Valvular structural deterioration is of particular concern for transcatheter aortic valve replacements due to their suspected shorter longevity and increasing use in younger patient populations. In this work we investigated the mechanical and microstructural changes in commercial TAVR valves composed of both glutaraldehyde fixed bovine and porcine pericardium (GLBP and GLPP) following accelerated wear testing (AWT) as outlined in ISO 5840 standards. This provided greater physiological relevance to the loading compared to previous studies and by utilizing digital image correlation we were able to obtain strain contours for each leaflet pre and post fatigue and identify sites of fatigue damage. The areas of greatest change in mechanical strain for each leaflet were then further probed using biaxial tensile testing, confocal microscopy, and electron microscopy. It was observed that overall strain decreased in the GLPP valves following AWT of 200 million cycles while the GLBP valve showed an increase in overall strain. Biaxial tensile testing showed a statistically significant reduction in stress for GLPP while no significant changes were seen for GLBP. Both confocal and electron microscopy showed a disruption to the gross collagen organization and fibrillar structure, including fragmentation, for GLPP but only the former for GLBP. However, further test data is required to confirm these findings and to provide a better understanding of this fatigue pathway is required such that it can be incorporated into both valve design and selection processes to improve overall longevity for both GLPP and GLBP devices.

Insights into structure and function of the active site of SoxAX cytochromes.

SoxAX cytochromes catalyze the formation of heterodisulfide bonds between inorganic sulfur compounds and a carrier protein, SoxYZ. They contain unusual His/Cys-ligated heme groups with complex spectroscopic signatures. The heme-ligating cysteine has been implicated in SoxAX catalysis, but neither the SoxAX spectroscopic properties nor its catalysis are fully understood at present. We have solved the first crystal structure for a group 2 SoxAX protein (SnSoxAX), where an N-terminal extension of SoxX forms a novel structure that supports dimer formation. Crystal structures of SoxAX with a heme ligand substitution (C236M) uncovered an inherent flexibility of this SoxA heme site, with both bonding distances and relative ligand orientation differing between asymmetric units and the new residue, Met(236), representing an unusual rotamer of methionine. The flexibility of the SnSoxAX(C236M) SoxA heme environment is probably the cause of the four distinct, new EPR signals, including a high spin ferric heme form, that were observed for the enzyme. Despite the removal of the catalytically active cysteine heme ligand and drastic changes in the redox potential of the SoxA heme (WT, -479 mV; C236M, +85 mV), the substituted enzyme was catalytically active in glutathione-based assays although with reduced turnover numbers (WT, 3.7 s(-1); C236M, 2.0 s(-1)). SnSoxAX(C236M) was also active in assays using SoxYZ and thiosulfate as the sulfur substrate, suggesting that Cys(236) aids catalysis but is not crucial for it. The SoxYZ-based SoxAX assay is the first assay for an isolated component of the Sox multienzyme system.

Cytochrome P450 is present in both ferrous and ferric forms in the resting state within intact Escherichia coli and hepatocytes.

Cytochrome P450 enzymes (P450s) are exceptionally versatile monooxygenases, mediating hydroxylations of unactivated C-H bonds, epoxidations, dealkylations, and N- and S-oxidations as well as other less common reactions. In the conventional view of the catalytic cycle, based upon studies of P450s in vitro, substrate binding to the Fe(III) resting state facilitates the first 1-electron reduction of the heme. However, the resting state of P450s in vivo has not been examined. In the present study, whole cell difference spectroscopy of bacterial (CYP101A1 and CYP176A1, i.e. P450cam and P450cin) and mammalian (CYP1A2, CYP2C9, CYP2A6, CYP2C19, and CYP3A4) P450s expressed within intact Escherichia coli revealed that both Fe(III) and Fe(II) forms of the enzyme are present in the absence of substrates. The relevance of this finding was supported by similar observations of Fe(II) P450 heme in intact rat hepatocytes. Electron paramagnetic resonance (EPR) spectroscopy of the bacterial forms in intact cells showed that a proportion of the P450 in cells was in an EPR-silent form in the native state consistent with the presence of Fe(II) P450. Coexpression of suitable cognate electron donors increased the degree of endogenous reduction to over 80%. A significant proportion of intracellular P450 remained in the Fe(II) form after vigorous aeration of cells. The addition of substrates increased the proportion of Fe(II) heme, suggesting a kinetic gate to heme reduction in the absence of substrate. In summary, these observations suggest that the resting state of P450s should be regarded as a mixture of Fe(III) and Fe(II) forms in both aerobic and oxygen-limited conditions.

Monoesterase activity of a purple acid phosphatase mimic with a cyclam platform.

The synthesis and characterization of a novel dinucleating ligand L (L=4,11-dimethyl-1,8-bis{2-[N-(di-2-pyridylmethyl)amino]ethyl}cyclam) and its µ-oxo-bridged diferric complex [(H(2)L){Fe(III)(2)(O)}(Cl)(4)](2+) are reported. This diiron(III) complex is the first example of a truly functional purple acid phosphatase (PAP) mimic as it accelerates the hydrolysis of the activated phosphomonoester 2,4-dinitrophenyl phosphate (DNPP). The spectroscopic and kinetic data indicate that only substrates that are monodentately bound to one of the two ferric ions can be attacked by a suitable nucleophile. This is, most probably, a terminal iron(III)-bound hydroxide. DFT calculations support this assumption and also highlight the importance of secondary interactions, exerted by the protonated cyclam platform, for the positioning and activation of the iron(III)-bound substrate. Similar effects are postulated in the native enzyme but addressed in PAP mimics for the first time.

Cu(II) coordination chemistry of patellamide derivatives: possible biological functions of cyclic pseudopeptides.

Two synthetic derivatives of the naturally occurring cyclic pseudooctapeptides patellamide  A-F and ascidiacyclamide, that is, H(4)pat(2), H(4)pat(3), as well as their Cu(II) complexes are described. These cyclic peptide derivatives differ from the naturally occurring macrocycles by the variation of the incorporated heterocyclic donor groups and the configuration of the amino acids connecting the heterocycles. The exchange of the oxazoline and thiazole groups by dimethylimidazoles or methyloxazoles leads to more rigid macrocycles, and the changes in the configuration of the side chains leads to significant differences in the folding of the cyclic peptides. These variations allow a detailed study of the various possible structural changes on the chemistry of the Cu(II) complexes formed. The coordination of Cu(II) with these macrocyclic species was monitored by high-resolution electrospray mass spectrometry (ESI-MS), spectrophotometric (UV/Vis) and circular dichroic (CD) titrations, and electron paramagnetic resonance (EPR) spectroscopy. Density functional theory (DFT) calculations and molecular mechanics (MM) simulations have been used to model the structures of the Cu(II) complexes and provide a detailed understanding of their geometric preferences and conformational flexibility. This is related to the Cu(II) coordination chemistry and the reactivity of the dinuclear Cu(II) complexes towards CO(2) fixation. The variation observed between the natural and various synthetic peptide systems enables conclusions about structure-reactivity correlations, and our results also provide information on why nature might have chosen oxazolines and thiazoles as incorporated heterocycles.

Spectroscopic and catalytic characterization of a functional Fe(III)Fe(II) biomimetic for the active site of uteroferrin and protein cleavage.

A mixed-valence complex, [Fe(III)Fe(II)L1(µ-OAc)(2)]BF(4)·H(2)O, where the ligand H(2)L1 = 2-{[[3-[((bis(pyridin-2-ylmethyl)amino)methyl)-2-hydroxy-5-methylbenzyl](pyridin-2-ylmethyl)amino]methyl]phenol}, has been studied with a range of techniques, and, where possible, its properties have been compared to those of the corresponding enzyme system purple acid phosphatase. The Fe(III)Fe(II) and Fe(III)(2) oxidized species were studied spectroelectrochemically. The temperature-dependent population of the S = 3/2 spin states of the heterovalent system, observed using magnetic circular dichroism, confirmed that the dinuclear center is weakly antiferromagnetically coupled (H = -2JS(1)·S(2), where J = -5.6 cm(-1)) in a frozen solution. The ligand-to-metal charge-transfer transitions are correlated with density functional theory calculations. The Fe(III)Fe(II) complex is electron paramagnetic resonance (EPR)-silent, except at very low temperatures (<2 K), because of the broadening caused by the exchange coupling and zero-field-splitting parameters being of comparable magnitude and rapid spin-lattice relaxation. However, a phosphate-bound Fe(III)(2) complex showed an EPR spectrum due to population of the S(tot) = 3 state (J= -3.5 cm(-1)). The phosphatase activity of the Fe(III)Fe(II) complex in hydrolysis of bis(2,4-dinitrophenyl)phosphate (k(cat.) = 1.88 × 10(-3) s(-1); K(m) = 4.63 × 10(-3) mol L(-1)) is similar to that of other bimetallic heterovalent complexes with the same ligand. Analysis of the kinetic data supports a mechanism where the initiating nucleophile in the phosphatase reaction is a hydroxide, terminally bound to Fe(III). It is interesting to note that aqueous solutions of [Fe(III)Fe(II)L1(µ-OAc)(2)](+) are also capable of protein cleavage, at mild temperature and pH conditions, thus further expanding the scope of this complex's catalytic promiscuity.

A direct comparison of the optically stimulated luminescent properties of BeO and Al2O3 for clinical in-vivo dosimetry.

Optically stimulated luminescence dosimetry is a relatively recent field of in-vivo dosimetry in clinical radiotherapy, developing over the last 20 years. As a pilot study, this paper presents a direct comparison between the sensitivity variance with use, stability of measurement and linearity of the current clinical standard Al2O3:C and a potential alternative, beryllium oxide. A set of ten optically stimulated luminescence dosimeters (OSLD), including five of each type, were used simultaneously and irradiated on a Versa HD linear accelerator. Having similar sensitivity, while Al2O3:C showed a relatively stable signal response from initial use, BeO was found to have a higher response to the same dose. However, BeO displayed a strong exponential decline from initial signal response following a model of [Formula: see text], reaching stability after approximately 10 irradiation cycles. BeO was shown to have potentially higher accuracy than Al2O3:C, with less variation between individual doses. Both OSLD showed good linearity between 0.2-5.0 Gy. Between these bounds, Al2O3:C demonstrated a strong linear response following the trend [Formula: see text], however beyond this showed deviation from linearity, resulting in a measured dose of [Formula: see text] Gy at 10.0 Gy dose delivery. BeO showed strong linearity across the full examined range of 0.2-10.0 Gy with following a model of [Formula: see text] Gy with a recorded dose at 10.0 Gy delivery as [Formula: see text] Gy. In conclusion, BeO does show large variance in sensitivity between individual OSLD and a considerable initial variance and decline in dose-response, however after pre-conditioning and individual normalisation to offset OSLD specific sensitivity BeO provides not only a viable alternative to Al2O3:C, but potentially provide higher accuracy, precision and reproducibility for in-vivo dosimetry.

Evaluation of Pericardial Tissues from Assorted Species as a Tissue-Engineered Heart Valve Material.

Decellularized pericardial tissue is a strong candidate for a TEHV material as ECM is present to guide cellular infiltration and fixed porcine and bovine pericardial tissue have existing use in bioprosthetic heart valves. In this work, we compare the mechanical and microstructural properties of decellularized-sterilized (DS) porcine, bovine, and bison pericardial tissues with respect to use as a TEHV. H&E staining was used to verify removal of cellular content post-decellularization and to evaluate collagen fiber structure. Additionally, uniaxial and biaxial tension testing were used to compare mechanical performance and, for the latter, acquire constitutive model parameters for subsequent finite element (FE) modeling. H&E staining revealed complete removal of cellular content and good collagen fiber structure. Tensile testing showed comparable mechanical strength between the three DS pericardial tissues and considerably stronger mechanical properties compared to native tissues. Bovine and bison DS pericardial tissues showed the strongest mechanical performance in the FE models with bison demonstrating the overall best mechanical characteristics. The increased thickness of bovine and bison tissues coupled with the strong mechanical behavior and ECM structure indicates that these materials will be resistant to damage until sufficient cellular infiltration has occurred such that damaged tissue can be repaired.

Finite element analysis in clinical patients with atherosclerosis.

Endovascular plaque composition is strongly related to stent strut stress and is responsible for strut fatigue, stent failure, and possible in-stent restenosis. To evaluate the effect of plaque on artery wall resistance to expansion we performed in silico analysis of atherosclerotic vessels. We generated finite element models from in vivo intravascular ultrasound virtual histology images to determine local artery surface stiffness and determined which plaque structures have the greatest influence. We validated the predictive capacity of our modeling approach by testing an atherosclerotic peripheral artery ex vivo with pressure-inflation testing at physiological pressures ranging from 10 to 200 mmHg. For this purpose, the in silico deformation of the arterial wall was compared to that observed ex vivo. We found that calcification had a positive effect on surface stiffness with fibrous plaque and necrotic core having negative effects. Additionally, larger plaque structures demonstrated significantly higher average surface stiffness and calcification located nearer the lumen was also shown to increase surface stiffness. Therefore, more developed plaques will have greater resistance to expansion and higher stent strut stress, with calcification located near the lumen further increasing stress in localized areas. Thus, it may be expected that such plaque structures may increase the likelihood of localized stent strut fracture.

Webinar and survey on quality management principles within the Australian and New Zealand ACPSEM Workforce.

Healthcare relies upon the accurate and safe delivery of patient care. This is only achievable when systems are developed to ensure high quality, robust outcomes, for instance quality management systems. The concept of quality management can take on a different meaning depending on the context in which it is found. To add complication, the amount of education required for quality management will vary depending on one's exposure to the implementation of quality systems. In part to address these issues, the Australasian College of Physical Scientists and Engineers in Medicine (ACPSEM) Queensland Branch held a quality management webinar for members and non-members across Australia and New Zealand. The purpose of the webinar was to educate and facilitate discussion regarding the application of quality management principles for the ACPSEM profession. In conjunction, a pre- and post-webinar survey was conducted to gain an insight into existing knowledge and attitudes within the professions governed by the ACPSEM and students undertaking related studies. This paper authored by the webinar speakers reintroduces the quality management principles that were discussed in webinar, exemplifies the importance of quality management skills within the ACPSEM professions and presents the results of the surveys, promoting the need for more educational resources on quality management tools.

Automatic Detection and Tracking of Marker Seeds Implanted in Prostate Cancer Patients using a Deep Learning Algorithm.

PURPOSE: Fiducial marker seeds are often used as a surrogate to identify and track the positioning of prostate volume in the treatment of prostate cancer. Tracking the movement of prostate seeds aids in minimizing the prescription dose spillage outside the target volume to reduce normal tissue complications. In this study, You Only Look Once (YOLO) v2™ (MathWorks™) convolutional neural network was employed to train ground truth datasets and develop a program in MATLAB that can visualize and detect the seeds on projection images obtained from kilovoltage (kV) X-ray volume imaging (XVI) panel (Elekta™). METHODS: As a proof of concept, a wax phantom containing three gold marker seeds was imaged, and kV XVI seed images were labeled and used as ground truth to train the model. The projection images were corrected for any panel shift using flex map data. Upon successful testing, labeled marker seeds and projection images of three patients were used to train a model to detect fiducial marker seeds. A software program was developed to display the projection images in real-time and predict the seeds using YOLO v2 and determine the centers of the marker seeds on each image. RESULTS: The fiducial marker seeds were successfully detected in 98% of images from all gantry angles; the variation in the position of the seed center was within ± 1 mm. The percentage difference between the ground truth and the detected seeds was within 3%. CONCLUSION: Our study shows that deep learning can be used to detect fiducial marker seeds in kV images in real time. This is an ongoing study, and work is underway to extend it to other sites for tracking moving structures with minimal effort.

A 3D printed phantom to assess MRI geometric distortion.

Geometric distortions in magnetic resonance can introduce significant uncertainties into applications such as radiotherapy treatment planning and need to be assessed as part of a comprehensive quality assurance program. We report the design, fabrication, and imaging of a custom 3D printed unibody MR distortion phantom along with quantitative image analysis.Methods: The internal cavity of the phantom is an orthogonal three-dimensional planar lattice, composed of 3 mm diameter rods spaced equidistantly at a 20 mm centre-centre offset repeating along the X, Y, and Z axes. The phantom featured an overall length of 308.5 mm, a width of 246 mm, and a height of 264 mm with lines on the external surface for phantom positioning matched to external lasers. The MR phantom was 3D printed in Nylon-12 using an advancement on traditional selective laser sintering (SLS) (HP Jet Fusion 3D-4200 machine). The phantom was scanned on a Toshiba Aquilion CT scanner to check the integrity of the 3D print and correct for any resultant issues. The phantom was then filled with NiSO4solution and scanned on a 3T PET-MR Siemens scanner for selected T1 and T2 sequences, from which distortion vectors were generated and analysed using in-house software written in Python.Results: All deviations of the node positions from the print design were less than 1 mm, with an average displacement of 0.228 mm. The majority of the deviations were smaller than the 0.692 mm pixel size for this dataset.Conclusion: A customised 3D printed MRI-phantom was successfully printed and tested for assessing geometric distortion on MRI scanners. 3D printed phantoms can be considered for clinics wishing to assess geometric distortions under specific conditions, but require resources for design, fabrication, commissioning, and verification.