OPTIma:simplifying calorimetry for proton computed tomography in high proton flux environments

Objective. Proton computed tomography (pCT) offers a potential route to reducing range uncertainties for proton therapy treatment planning, however the current trend towards high current spot scanning treatment systems leads to high proton fluxes which are challenging for existing systems. Here we demonstrate a novel approach to energy reconstruction, referred to as ‘de-averaging’, which allows individual proton energies to be recovered using only a measurement of their integrated energy without the need for spatial information from the calorimeter. Approach. The method is evaluated in the context of the Optimising Proton Therapy through Imaging (OPTIma) system which uses a simple, relatively inexpensive, scintillator-based calorimeter that reports only the integrated energy deposited by all protons within a cyclotron period, alongside a silicon strip based tracking system capable of reconstructing individual protons in a high flux environment. GEANT4 simulations have been performed to examine the performance of such a system at a modern commercial cyclotron facility using a σ ≈ 10 mm beam for currents in the range 10–50 pA at the nozzle. Main results. Apart from low-density lung tissue, a discrepancy of less than 1% on the Relative Stopping Power is found for all other considered tissues when embedded within a 150 mm spherical Perspex phantom in the 10–30 pA current range, and for some tissues even up to 50 pA. Significance. By removing the need for the calorimeter system to provide spatial information, it is hoped that the de-averaging approach can facilitate clinically relevant, cost effective and less complex calorimeter systems for performing high current pCTs

Hit-hard and early versus step-up treatment in severe sarcoidosis

Purpose of reviewThe treatment of sarcoidosis remains uncertain, despite 70 years of study. The conventional approach is to initiate corticosteroids in individuals who require treatment. The position of more aggressive regimes is unknown.Recent findingsRecent recognition that many patients will require prolonged therapy, and the observation that corticosteroids lead to overt and insidious toxicities, have led to suggestions that steroid-sparing medications be used earlier in the management of sarcoidosis. Individuals with poor prognostic features, designated as 'high-risk' sarcoidosis may, especially benefit from a broader palette of therapeutic options in the initial treatment regimen. An even more aggressive approach, known as 'top-down' or 'hit-hard and early' therapy has emerged in the fields of gastroenterology and rheumatology in the past 15 years, on the premise that highly effective early control of inflammation leads to better outcomes. These regimens typically involve early initiation of biologic therapies.SummaryFor certain subpopulations of sarcoidosis patients, 'top-down' therapy could be helpful. Severe pulmonary sarcoidosis, neurosarcoidosis, cardiac sarcoidosis and multiorgan sarcoidosis are phenotypes that may be most relevant for revised therapeutic algorithms. Precision medicine approaches and randomized trials will be necessary to confirm a role for top-down therapy in the routine management of sarcoidosis

Deforming glassy polystyrene: Influence of pressure, thermal history, and deformation mode on yielding and hardening

The toughness of a polymer glass is determined by the interplay of yielding, strain softening, and strain hardening. Molecular-dynamics simulations of a typical polymer glass, atactic polystyrene, under the influence of active deformation have been carried out to enlighten these processes. It is observed that the dominant interaction for the yield peak is of interchain nature and for the strain hardening of intrachain nature. A connection is made with the microscopic cage-to-cage motion. It is found that the deformation does not lead to complete erasure of the thermal history but that differences persist at large length scales. Also we find that the strain-hardening modulus increases with increasing external pressure. This new observation cannot be explained by current theories such as the one based on the entanglement picture and the inclusion of this effect will lead to an improvement in constitutive modeling

Non-Gaussian nature of glassy dynamics by cage to cage motion

A model based on a single Brownian particle moving in a periodic effective field is used to understand the non-Gaussian dynamics in glassy systems of cage escape and subsequent recaging, often thought to be caused by a heterogeneous glass structure. The results are compared to molecular-dynamics simulations of systems with varying complexity: quasi-two-dimensional colloidlike particles, atactic polystyrene, and a dendritic glass. The model nicely describes generic features of all three topologically different systems, in particular around the maximum of the non-Gaussian parameter. This maximum is a measure for the average distance between cages

Field-theoretic simulation of block copolymers at experimentally-relevant molecular weights

Field-theoretic simulation (FTS) offers an efficient means of predicting the equilibrium behavior of high-molecular-weight structured polymers, provided one is able to deal with the strong ultraviolet (UV) divergence that occurs at realistic molecular weights. Here melts of lamellar-forming diblock copolymer are studied using a Monte Carlo version (MC-FTS), where the composition field fluctuates while the pressure field follows the mean-field approximation. We are able to control the UV divergence by introducing a new effective Flory-Huggins interaction parameter, $\chi_e$, thereby permitting MC-FTS for molecular weights extending down to values characteristic of experiment. Results for the disordered-state structure function, the layer spacing and compressibility of the ordered lamellar phase, and the position of the order-disorder transition (ODT) show excellent agreement with recent particle-based simulation. Given the immense versatility of FTS, this opens up the opportunity for quantitative studies on a wide range of more complicated block copolymer systems

DenResCov-19: a deep transfer learning network for robust automatic classification of COVID-19, pneumonia, and tuberculosis from X-rays

The global pandemic of coronavirus disease 2019 (COVID-19) is continuing to have a significant effect on the well-being of the global population, thus increasing the demand for rapid testing, diagnosis, and treatment. As COVID-19 can cause severe pneumonia, early diagnosis is essential for correct treatment, as well as to reduce the stress on the healthcare system. Along with COVID-19, other etiologies of pneumonia and Tuberculosis (TB) constitute additional challenges to the medical system. Pneumonia (viral as well as bacterial) kills about 2 million infants every year and is consistently estimated as one of the most important factor of childhood mortality (according to the World Health Organization). Chest X-ray (CXR) and computed tomography (CT) scans are the primary imaging modalities for diagnosing respiratory diseases. Although CT scans are the gold standard, they are more expensive, time consuming, and are associated with a small but significant dose of radiation. Hence, CXR have become more widespread as a first line investigation. In this regard, the objective of this work is to develop a new deep transfer learning pipeline, named DenResCov-19, to diagnose patients with COVID-19, pneumonia, TB or healthy based on CXR images. The pipeline consists of the existing DenseNet-121 and the ResNet-50 networks. Since the DenseNet and ResNet have orthogonal performances in some instances, in the proposed model we have created an extra layer with convolutional neural network (CNN) blocks to join these two models together to establish superior performance as compared to the two individual networks. This strategy can be applied universally in cases where two competing networks are observed. We have tested the performance of our proposed network on two-class (pneumonia and healthy), three-class (COVID-19 positive, healthy, and pneumonia), as well as four-class (COVID-19 positive, healthy, TB, and pneumonia) classification problems. We have validated that our proposed network has been able to successfully classify these lung-diseases on our four datasets and this is one of our novel findings. In particular, the AUC-ROC are 99.60, 96.51, 93.70, 96.40% and the F1 values are 98.21, 87.29, 76.09, 83.17% on our Dataset X-Ray 1, 2, 3, and 4 (DXR1, DXR2, DXR3, DXR4), respectively

Turbulence anisotropy and the SO(3) description

We study strongly turbulent windtunnel flows with controlled anisotropy. Using a recent formalism based on angular momentum and the irreducible representations of the SO(3) rotation group, we attempt to extract this anisotropy from the angular dependence of second-order structure functions. Our instrumentation allows a measurement of both the separation and the angle dependence of the structure function. In axisymmetric turbulence which has a weak anisotropy, this more extended information produces ambiguous results. In more strongly anisotropic shear turbulence, the SO(3) description enables one to find the anisotropy scaling exponent. The key quality of the SO(3) description is that structure functions are a mixture of algebraic functions of the scale with exponents ordered such that the contribution of anisotropies diminishes at small scales. However, we find that in third-order structure functions of homogeneous shear turbulence the anisotropic contribution is always large and of the same order of magnitude as the isotropic part. Our results concern the minimum instrumentation needed to determine the parameters of the SO(3) description, and raise several questions about its ability to describe the angle dependence of high-order structure functions

Characterization of the PF-ILD phenotype in patients with advanced pulmonary sarcoidosis

Background: Advanced pulmonary sarcoidosis causes significant morbidity and can lead to death. Large trials demonstrated efficacy of antifibrotics in patients with progressive fibrosing interstitial lung diseases (PF-ILD), including a few with sarcoidosis. To date, little is known about this progressive fibrosing phenotype in sarcoidosis. Diffusion capacity of carbon monoxide (DLCO) may be a useful functional marker to screen for advanced pulmonary sarcoidosis. In this study, we describe a cohort with advanced pulmonary sarcoidosis and we gain insights in the progressive fibrosing phenotype in sarcoidosis. Methods: Patients with sarcoidosis and a DLCO 10% fibrosis on HRCT meeting the criteria for ILD-progression within 24 months were labelled as PF-ILD. With Cox-regression analysis predictors of mortality were established. Results: 106 patients with a DLCO 10% fibrosis on HRCT. Independent predictors of mortality and lung transplantation in the whole cohort are PH, PF-ILD and UIP-like pattern. Conclusion: In conclusion, within this group with advanced pulmonary sarcoidosis disease course varied widely from great functional improvement to death. PF-ILD patients had higher mortality rate than the mortality in the overall pulmonary sarcoidosis group. Future research should focus on the addition of antifibrotics in these patients. Trial registration retrospectively registere

Mechanical Properties of Glassy Polyethylene Nanofibers via Molecular Dynamics Simulations

The extent to which the intrinsic mechanical properties of polymer fibers depend on physical size has been a matter of dispute that is relevant to most nanofiber applications. Here, we report the elastic and plastic properties determined from molecular dynamics simulations of amorphous, glassy polymer nanofibers with diameter ranging from 3.7 to 17.7 nm. We find that, for a given temperature, the Young’s elastic modulus E decreases with fiber radius and can be as much as 52% lower than that of the corresponding bulk material. Poisson’s ratio ν of the polymer comprising these nanofibers was found to decrease from a value of 0.3 to 0.1 with decreasing fiber radius. Our findings also indicate that a small but finite stress exists on the simulated nanofibers prior to elongation, attributable to surface tension. When strained uniaxially up to a tensile strain of ε = 0.2 over the range of strain rates and temperatures considered, the nanofibers exhibit a yield stress σy between 40 and 72 MPa, which is not strongly dependent on fiber radius; this yield stress is approximately half that of the same polyethylene simulated in the amorphous bulk.DuPont MIT AllianceDuPont (Firm) (Young Professor Award

Reduced expression of monocyte CD200R is associated with enhanced proinflammatory cytokine production in sarcoidosis

In sarcoidosis, the proinflammatory cytokines interferon gamma, tumour necrosis factor and interleukin-6 are released by monocyte-derived macrophages and lymphocytes in the lungs and other affected tissues. Regulatory receptors expressed on monocytes and macrophages act to suppress cytokine production, and reduced expression of regulatory receptors may thus promote tissue inflammation. The aim of this study was to characterise the role of regulatory receptors on blood monocytes in patients with sarcoidosis. Cytokine release in response to stimulation of whole blood was measured in healthy controls and Caucasian non-smoking patients with sarcoidosis who were not taking disease modifying therapy. Expression of the regulatory molecules IL-10R, SIRP-α/β, CD47, CD200R, and CD200L was measured by flow cytometry, and functional activity was assessed using blocking antibodies. Stimulated whole blood and monocytes from patients with sarcoidosis produced more TNF and IL-6 compared with healthy controls. 52.9% of sarcoidosis patients had monocytes characterised by low expression of CD200R, compared with 11.7% of controls (p < 0.0001). Patients with low monocyte CD200R expression produced higher levels of proinflammatory cytokines. In functional studies, blocking the CD200 axis increased production of TNF and IL-6. Reduced expression of CD200R on monocytes may be a mechanism contributing to monocyte and macrophage hyper-activation in sarcoidosis