A Lipid-Structured Model of Atherosclerosis with Macrophage Proliferation

Atherosclerotic plaques are fatty deposits that form in the walls of major arteries and are one of the major causes of heart attacks and strokes. Macrophages are the main immune cells in plaques and macrophage dynamics influence whether plaques grow or regress. Macrophage proliferation is a key process in atherosclerosis, particularly in the development of mid-stage plaques, but very few mathematical models include proliferation. In this paper we reframe the lipid-structured model of Ford et al. (J Theor Biol 479:48–63, 2019. https://doi.org/10.1016/j.jtbi.2019.07.003) to account for macrophage proliferation. Proliferation is modelled as a non-local decrease in the lipid structural variable. Steady state analysis indicates that proliferation assists in reducing eventual necrotic core lipid content and spreads the lipid load of the macrophage population amongst the cells. The contribution of plaque macrophages from proliferation relative to recruitment from the bloodstream is also examined. The model suggests that a more proliferative plaque differs from an equivalent (defined as having the same lipid content and cell numbers) recruitment-dominant plaque in the way lipid is distributed amongst the macrophages. The macrophage lipid distribution of an equivalent proliferation-dominant plaque is less skewed and exhibits a local maximum near the endogenous lipid content

How Do Surgeon Preferences and Technique Variances Affect Outcome?

The goal of the research project is to create a blue-print of a robot-assisted hysterectomy procedure to support design and evaluation of technology to enhance system performance. To create this blue-print, we will conduct a task analysis, model the cognitive task flow and decision making, and develop a simulation of the hysterectomy procedure. The surgical simulation will be used as a platform to train surgeons on robotic-assisted hysterectomies, as well as to assess learning and performance. Additionally, it will be used to design and develop techniques and novel technology to support surgeons in their performance of the surgery. Current research efforts are focused on the task analysis step. Data collection included observations in the hospital operating room, interviews with surgeons and nurses, analysis of surgery instructional videos and textbooks. A hierarchical task decomposition has been conducted. Thus far, results of the task analysis reveal several different types of hysterectomies and large variance in surgical techniques based on each surgeon’s preference. These findings will be validated by expert surgeons, and supplemented with a cognitive task analysis. In the next phase of the research project, we will identify several critical decision points within the surgical procedure that include variations in the use of surgical tools or variations in the sequence of actions. For example, the use of a uterine manipulator during the hysterectomy procedure seems to have an impact on the surgeon’s ease, speed, and accuracy while performing the procedure. These variations will be modeled and incorporated into the surgical simulation during development. Ultimately, the simulator will be used to train and assess the physician’s performance. It will also allow us to analyze the difference in techniques and how that affects patient outcome. A surgical simulation that has been designed and developed based on a systematic task analysis and cognitive model will allow us to more accurately study the requirements and constraints of the surgical environment, and support future innovate to enhance surgical performance and patient safety.https://corescholar.libraries.wright.edu/urop_celebration/1142/thumbnail.jp

Blood Lipoproteins Shape the Phenotype and Lipid Content of Early Atherosclerotic Lesion Macrophages: A Dual-Structured Mathematical Model

Macrophages in atherosclerotic lesions exhibit a spectrum of behaviours or phenotypes. The phenotypic distribution of monocyte-derived macrophages (MDMs), its correlation with MDM lipid content, and relation to blood lipoprotein densities are not well understood. Of particular interest is the balance between low density lipoproteins (LDL) and high density lipoproteins (HDL), which carry bad and good cholesterol respectively. To address these issues, we have developed a mathematical model for early atherosclerosis in which the MDM population is structured by phenotype and lipid content. The model admits a simpler, closed subsystem whose analysis shows how lesion composition becomes more pathological as the blood density of LDL increases relative to the HDL capacity. We use asymptotic analysis to derive a power-law relationship between MDM phenotype and lipid content at steady-state. This relationship enables us to understand why, for example, lipid-laden MDMs have a more inflammatory phenotype than lipid-poor MDMs when blood LDL lipid density greatly exceeds HDL capacity. We show further that the MDM phenotype distribution always attains a local maximum, while the lipid content distribution may be unimodal, adopt a quasi-uniform profile or decrease monotonically. Pathological lesions exhibit a local maximum in both the phenotype and lipid content MDM distributions, with the maximum at an inflammatory phenotype and near the lipid content capacity respectively. These results illustrate how macrophage heterogeneity arises in early atherosclerosis and provide a framework for future model validation through comparison with single-cell RNA sequencing data

The discovery of 2.78 hour periodic modulation of the X-ray flux from globular cluster source Bo 158 in M31

We report the discovery of periodic intensity dips in the X-ray source XMMU J004314.1+410724, in the globular cluster Bo158 in M31. The X-ray flux was modulated by ~83% at a period of 2.78 hr (10017 s) in an XMM-Newton observation taken 2002 Jan 6-7. The X-ray intensity dips show no energy dependence. We detected weaker dips with the same period in observations taken 2000 June 25 (XMM-Newton) and 1991 June 26 (ROSAT/PSPC). The amplitude of the modulation has been found to be anticorrelated with source X-ray flux: it becomes lower when the source intensity rises. The energy spectrum of Bo158 was stable from observation to observation, with a characteristic cutoff at ~4-6 keV. The photo-electric absorption was consistent with the Galactic foreground value. No significant spectral changes were seen in the course of the dips. If the 2.78 hr cycle is the binary period of Bo158 the system is highly compact, with a binary separation of ~10e11 cm. The association of the source with a globular cluster, together with spectral parameters consistent with Galactic neutron star sources, suggests that X-rays are emitted by an accreting neutron star. The properties of Bo 158 are somewhat reminiscent of the Galactic X-ray sources exhibiting a dip-like modulations. We discuss two possible mechanisms explaining the energy-independent modulation observed in Bo 158: i) the obscuration of the central source by highly ionized material that scatters X-rays out of the line of sight; ii) partial covering of an extended source by an opaque absorber which occults varying fractions of the source.Comment: 10 pages, 4 figures, ApJ, submitted, uses emulateapj styl

High-fidelity single-shot singlet-triplet readout of precision-placed donors in silicon

In this work we perform direct single-shot readout of the singlet-triplet states in exchange coupled electrons confined to precision-placed donor atoms in silicon. Our method takes advantage of the large energy splitting given by the Pauli-spin blockaded (2,0) triplet states, from which we can achieve a single-shot readout fidelity of 98.4 ± 0.2%. We measure the triplet-minus relaxation time to be of the order 3 s at 2.5 T and observe its predicted decrease as a function of magnetic field, reaching 0.5 s at 1 T

Confirmation of co-denitrification in grazed grassland

Pasture-based livestock systems are often associated with losses of reactive forms of nitrogen (N) to the environment. Research has focused on losses to air and water due to the health, economic and environmental impacts of reactive N. Di-nitrogen (N₂) emissions are still poorly characterized, both in terms of the processes involved and their magnitude, due to financial and methodological constraints. Relatively few studies have focused on quantifying N₂ losses in vivo and fewer still have examined the relative contribution of the different N₂ emission processes, particularly in grazed pastures. We used a combination of a high ¹⁵N isotopic enrichment of applied N with a high precision of determination of ¹⁵N isotopic enrichment by isotope-ratio mass spectrometry to measure N₂ emissions in the field. We report that 55.8 g N m⁻² (95%, CI 38 to 77 g m⁻²) was emitted as N₂ by the process of co-denitrification in pastoral soils over 123 days following urine deposition (100 g N m⁻²), compared to only 1.1 g N m⁻² (0.4 to 2.8 g m⁻²) from denitrification. This study provides strong evidence for co-denitrification as a major N₂ production pathway, which has significant implications for understanding the N budgets of pastoral ecosystems

First results from the Very Small Array -- I. Observational methods

The Very Small Array (VSA) is a synthesis telescope designed to image faint structures in the cosmic microwave background on degree and sub-degree angular scales. The VSA has key differences from other CMB interferometers with the result that different systematic errors are expected. We have tested the operation of the VSA with a variety of blank-field and calibrator observations and cross-checked its calibration scale against independent measurements. We find that systematic effects can be suppressed below the thermal noise level in long observations; the overall calibration accuracy of the flux density scale is 3.5 percent and is limited by the external absolute calibration scale.Comment: 9 pages, 10 figures, MNRAS in press (Minor revisions

Follow-up observations at 16 and 33 GHz of extragalactic sources from WMAP 3-year data: I - Spectral properties

We present follow-up observations of 97 point sources from the Wilkinson Microwave Anisotropy Probe (WMAP) 3-year data, contained within the New Extragalactic WMAP Point Source (NEWPS) catalogue between declinations of -4 and +60 degrees; the sources form a flux-density-limited sample complete to 1.1 Jy (approximately 5 sigma) at 33 GHz. Our observations were made at 16 GHz using the Arcminute Microkelvin Imager (AMI) and at 33 GHz with the Very Small Array (VSA). 94 of the sources have reliable, simultaneous -- typically a few minutes apart -- observations with both telescopes. The spectra between 13.9 and 33.75 GHz are very different from those of bright sources at low frequency: 44 per cent have rising spectra (alpha < 0.0), where flux density is proportional to frequency^-alpha, and 93 per cent have spectra with alpha < 0.5; the median spectral index is 0.04. For the brighter sources, the agreement between VSA and WMAP 33-GHz flux densities averaged over sources is very good. However, for the fainter sources, the VSA tends to measure lower values for the flux densities than WMAP. We suggest that the main cause of this effect is Eddington bias arising from variability.Comment: 12 pages, 13 figures, submitted to MNRA

Building confidence in projections of the responses of living marine resources to climate change

The Fifth Assessment Report of the Intergovernmental Panel on Climate Change highlights that climate change and ocean acidification are challenging the sustainable management of living marine resources (LMRs). Formal and systematic treatment of uncertainty in existing LMR projections, however, is lacking. We synthesize knowledge of how to address different sources of uncertainty by drawing from climate model intercomparison efforts. We suggest an ensemble of available models and projections, informed by observations, as a starting point to quantify uncertainties. Such an ensemble must be paired with analysis of the dominant uncertainties over different spatial scales, time horizons, and metrics. We use two examples: (i) global and regional projections of Sea Surface Temperature and (ii) projection of changes in potential catch of sablefish (Anoplopoma fimbria) in the 21st century, to illustrate this ensemble model approach to explore different types of uncertainties. Further effort should prioritize understanding dominant, undersampled dimensions of uncertainty, as well as the strategic collection of observations to quantify, and ultimately reduce, uncertainties. Our proposed framework will improve our understanding of future changes in LMR and the resulting risk of impacts to ecosystems and the societies under changing ocean conditions