LVNet: Light-Weight Model for Left Ventricle Segmentation for Short Axis Views in Echocardiographic Imaging

Lightweight segmentation models are becoming more popular for fast diagnosis on small and low cost medical imaging devices. This study focuses on the segmentation of the left ventricle (LV) in cardiac ultrasound (US) images. A new lightweight model [LV network (LVNet)] is proposed for segmentation, which gives the benefits of requiring fewer parameters but with improved segmentation performance in terms of Dice score (DS). The proposed model is compared with state-of-the-art methods, such as UNet, MiniNetV2, and fully convolutional dense dilated network (FCdDN). The model proposed comes with a post-processing pipeline that further enhances the segmentation results. In general, the training is done directly using the segmentation mask as the output and the US image as the input of the model. A new strategy for segmentation is also introduced in addition to the direct training method used. Compared with the UNet model, an improvement in DS performance as high as 5% for segmentation with papillary (WP) muscles was found, while showcasing an improvement of 18.5% when the papillary muscles are excluded. The model proposed requires only 5% of the memory required by a UNet model. LVNet achieves a better trade-off between the number of parameters and its segmentation performance as compared with other conventional models.</p

Effect of Upstream Turbine Tip Speed Variations on Downstream Turbine Performance

AbstractA wake study and combined power output analysis of an array of two model wind turbines is presented. In a wind farm arrangement wakes behind the upstream turbines directly affect the performance and structural loads of the downstream turbines. In this analysis the characteristics of the mean and turbulent wake flow behind an upstream model turbine is directly related to the performance characteristics of a downstream rotor located at three different downstream locations. First the influence of the upstream turbine's tip speed ratio variation from design conditions on the wake flow and the downstream turbine performance is analyzed. Thereafter, also the turbulence intensity level at the wind tunnel inlet is varied from low (laboratory conditions, TI=0.23%) to high (atmospheric conditions, TI=10.0%). Finally, the combined power output of the two turbine array is evaluated for a matrix of the different scenarios.A significant influence of the background turbulence level on the wake recovery is observed, especially for the intermediate separation distance of x/D=5. Controlling the upstream turbine's tip speed ratio away from its design point does not result in a significant increase in combined power output. Only for the case of low turbine separation distance (x/D=3) and low background turbulence the added kinetic energy in the wake can be recovered by the downstream turbine. For higher turbine separation distances and higher background turbulence, the added kinetic energy diffuses into the freestream flow and cannot be recovered anymore. In average, the combined efficiency is observed to increase by about 2.5% with every additional rotor diameter of turbine separation distance. Thus, this analysis suggests an accurate management of the upstream turbine tip speed ratio in dependence of background turbulence and turbine separation distance when optimizing the power output of a wind farm

<i>Staphylococcus aureus</i> enterotoxins induce FOXP3 in neoplastic T cells in Sézary syndrome

Sezary syndrome (SS) is a heterogeneous leukemic subtype of cutaneous T-cell lymphoma (CTCL) with generalized erythroderma, lymphadenopathy, and a poor prognosis. Advanced disease is invariably associated with severe immune dysregulation and the majority of patients die from infectious complications caused by microorganisms such as, Staphylococcus aureus, rather than from the lymphoma per se. Here, we examined if staphylococcal enterotoxins (SE) may shape the phenotype of malignant SS cells, including expression of the regulatory T-cell-associated marker FOXP3. Our studies with primary and cultured malignant cells show that SE induce expression of FOXP3 in malignant cells when exposed to nonmalignant cells. Mutations in the MHC class II binding domain of SE-A (SEA) largely block the effect indicating that the response relies at least in part on the MHC class II-mediated antigen presentation. Transwell experiments show that the effect is induced by soluble factors, partly blocked by anti-IL-2 antibody, and depends on STAT5 activation in malignant cells. Collectively, these findings show that SE stimulate nonmalignant cells to induce FOXP3 expression in malignant cells. Thus, differences in exposure to environmental factors, such as bacterial toxins may explain the heterogeneous FOXP3 expression in malignant cells in SS.Dermatology-oncolog

Staphylococcal enterotoxin A (SEA) stimulates STAT3 activation and IL-17 expression in cutaneous T-cell lymphoma

Cutaneous T-cell lymphoma (CTCL) is characterized by proliferation of malignant T cells in a chronic inflammatory environment. With disease progression, bacteria colonize the compromised skin barrier and half of CTCL patients die of infection rather than from direct organ involvement by the malignancy. Clinical data indicate that bacteria play a direct role in disease progression, but little is known about the mechanisms involved. Here, we demonstrate that bacterial isolates containing staphylococcal enterotoxin A (SEA) from the affected skin of CTCL patients, as well as recombinant SEA, stimulate activation of signal transducer and activator of transcription 3 (STAT3) and upregulation of interleukin (IL)-17 in immortalized and primary patient-derived malignant and nonmalignant T cells. Importantly, SEA induces STAT3 activation and IL-17 expression in malignant T cells when cocultured with nonmalignant T cells, indicating an indirect mode of action. In accordance, malignant T cells expressing an SEA-nonresponsive T-cell receptor variable region β chain are nonresponsive to SEA in monoculture but display strong STAT3 activation and IL-17 expression in cocultures with SEA-responsive nonmalignant T cells. The response is induced via IL-2 receptor common γ chain cytokines and a Janus kinase 3 (JAK3)-dependent pathway in malignant T cells, and blocked by tofacitinib, a clinical-grade JAK3 inhibitor. In conclusion, we demonstrate that SEA induces cell cross talk-dependent activation of STAT3 and expression of IL-17 in malignant T cells, suggesting a mechanism whereby SEA-producing bacteria promote activation of an established oncogenic pathway previously implicated in carcinogenesis

Malignant inflammation in cutaneous T-cell lymphoma: a hostile takeover

Cutaneous T-cell lymphomas (CTCL) are characterized by the presence of chronically inflamed skin lesions containing malignant T cells. Early disease presents as limited skin patches or plaques and exhibits an indolent behavior. For many patients, the disease never progresses beyond this stage, but in approximately one third of patients, the disease becomes progressive, and the skin lesions start to expand and evolve. Eventually, overt tumors develop and the malignant T cells may disseminate to the blood, lymph nodes, bone marrow, and visceral organs, often with a fatal outcome. The transition from early indolent to progressive and advanced disease is accompanied by a significant shift in the nature of the tumor-associated inflammation. This shift does not appear to be an epiphenomenon but rather a critical step in disease progression. Emerging evidence supports that the malignant T cells take control of the inflammatory environment, suppressing cellular immunity and anti-tumor responses while promoting a chronic inflammatory milieu that fuels their own expansion. Here, we review the inflammatory changes associated with disease progression in CTCL and point to their wider relevance in other cancer contexts. We further define the term "malignant inflammation" as a pro-tumorigenic inflammatory environment orchestrated by the tumor cells and discuss some of the mechanisms driving the development of malignant inflammation in CTCL

Stroke genetics informs drug discovery and risk prediction across ancestries

Previous genome-wide association studies (GWASs) of stroke — the second leading cause of death worldwide — were conducted predominantly in populations of European ancestry1,2. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis3, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach4, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry5. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries

Two-phase Material Point Method applied to the study of cone penetration

This paper presents numerical simulations of Cone Penetration Test (CPT) in water-saturated soft soils taking into account pore pressure dissipation during installation. Besides modelling interaction between soil skeleton and pore fluid, the problem involves large soil deformations in the vicinity of the penetrometer, soil\u2013structure interaction, and complex non-linear response of soil. This makes such simulations challenging. Depending on the soil\u2019s permeability and compressibility, undrained, partially drained or drained conditions might occur. Partially drained conditions are commonly encountered in soils such as silts and sand\u2013clay mixtures. However, this is often neglected in CPT interpretation, which may lead to inaccurate estimates of soil properties. This paper aims at improving the understanding of the penetration process in different drainage conditions through advanced numerical analyses. A two-phase Material Point Method is applied to simulate large soil deformations and generation and dissipation of excess pore pressures during penetration. The constitutive behaviour of soil is modelled with the Modified Cam Clay model. Numerical results are compared with experimental data showing good agreement

LVNet: Light-Weight Model for Left Ventricle Segmentation for Short Axis Views in Echocardiographic Imaging

Lightweight segmentation models are becoming more popular for fast diagnosis on small and low cost medical imaging devices. This study focuses on the segmentation of the left ventricle (LV) in cardiac ultrasound (US) images. A new lightweight model [LV network (LVNet)] is proposed for segmentation, which gives the benefits of requiring fewer parameters but with improved segmentation performance in terms of Dice score (DS). The proposed model is compared with state-of-the-art methods, such as UNet, MiniNetV2, and fully convolutional dense dilated network (FCdDN). The model proposed comes with a post-processing pipeline that further enhances the segmentation results. In general, the training is done directly using the segmentation mask as the output and the US image as the input of the model. A new strategy for segmentation is also introduced in addition to the direct training method used. Compared with the UNet model, an improvement in DS performance as high as 5% for segmentation with papillary (WP) muscles was found, while showcasing an improvement of 18.5% when the papillary muscles are excluded. The model proposed requires only 5% of the memory required by a UNet model. LVNet achieves a better trade-off between the number of parameters and its segmentation performance as compared with other conventional models

Effects of resin harvesting on the status of the Agathis philippinensis population in the Cleopatra's Needle Critical Habitat, the Philippines

In Palawan, the Philippines, a biological hotspot was turned into a protected area, called Cleopatra’s Needle Critical Habitat (CNCH). The most important goals of the CNCH are to conserve the rich endemic biodiversity and to maintain the culture of the Batak, a group of indigenous people who depend on forest resources for their livelihood. As resin extraction from Agathis philippinensis is a key component of the income of the Batak people, it is important to study the scope for sustainable exploitation of this species. This study focused on the effects of resin harvesting on the physical status and mortality of A. philippinensis trees in 15 subpopulations within the CNCH. These population characteristics were related to the intensity of resin harvest and the distance to communities. We found that the physical tree status deteriorated and the proportion of dead trees increased with harvest intensity and proximity to communities. These results indicate that overharvesting of the resource is taking place, which may lead to prolonged recruitment failure and population decline of A. philippinensisin the study area

Undercarboxylated matrix Gla protein is associated with indices of heart failure and mortality in symptomatic aortic stenosis

Ueland T, Gullestad L, Dahl CP, Aukrust P, Aakhus S, Solberg OG, Vermeer C, Schurgers LJ (Research Institute for Internal Medicine, University of Oslo, Oslo; University of Oslo, Oslo, Norway; and VitaK &amp; Cardiovascular Research Institute CARIM (CV, LS), Maastricht University, Maastricht, The Netherlands) Undercarboxylated matrix Gla protein is associated with indices of heart failure and mortality in symptomatic aortic stenosis. J Intern Med 2010; 268: 483-492. Objective. Matrix Gla protein (MGP) is a calcification inhibitor and alterations in circulating MGP have been observed in different populations characterized by vascular calcification. We hypothesized that patients with calcific valvular aortic stenosis (AS) would have dysregulated circulating MGP levels. Design and subjects. We examined plasma levels of nonphosphorylated carboxylated and undercarboxylated MGP (dp-cMGP and dp-ucMGP, respectively) in 147 patients with symptomatic severe AS and in matched healthy controls. Main outcome measures. We further investigated the relationship between MGP levels and aortic pressure gradients and valve area by echocardiography and measures of heart failure. Finally, we assessed the prognostic value of elevated plasma dp-ucMGP level in relation to all-cause mortality in patients with AS. Results. We found markedly enhanced plasma levels of dp-cMGP and in particular of dp-ucMGP in patients with symptomatic AS. Although only weak correlations were found with the degree of AS, circulating dp-ucMGP was associated with cardiac function and long-term mortality in multivariate analysis. Conclusions. A dysregulated MGP system may have a role in the development of left ventricular dysfunction in patients with symptomatic AS