Drug-eluting embolic transarterial chemoembolization (DEE-TACE) improves the overall survival of hepatocellular carcinoma (HCC), but the agents used are not tailored to HCC. Our patented liposomal ...formulation enables the loading and elution of targeted therapies onto DEEs. This study aimed to establish the safety, feasibility, and pharmacokinetics of sorafenib or regorafenib DEE-TACE in a VX2 model. DEE-TACE was performed in VX2 hepatic tumors in a selective manner until stasis using liposomal sorafenib- or regorafenib-loaded DEEs. The animals were euthanized at 1, 24, and 72 h timepoints post embolization. Blood samples were taken for pharmacokinetics at 5 and 20 min and at 1, 24, and 72 h. Measurements of sorafenib or regorafenib were performed in all tissue samples on explanted hepatic tissue using the same mass spectrometry method. Histopathological examinations were carried out on tumor tissues and non-embolized hepatic specimens. DEE-TACE was performed on 23 rabbits. The plasma concentrations of sorafenib and regorafenib were statistically significantly several folds lower than the embolized liver at all examined timepoints. This study demonstrates the feasibility of loading sorafenib or regorafenib onto commercially available DEEs for use in TACE. The drugs eluted locally without release into systemic circulation.
Background Patients diagnosed with locally advanced pancreatic cancer are usually not eligible for surgical resection because of significant vascular involvement. Stereotactic body radiation therapy ...and chemotherapy are the treatments recommended by the National Comprehensive Cancer Network criteria. For patients who do not respond to or tolerate stereotactic body radiation therapy and/or chemotherapy, a new option is irreversible electroporation. Irreversible electroporation is a nonthermal minimally invasive ablation technique that uses electrical pulses to induce apoptosis of tumor cells without damage to the extracellular matrix, thus preserving ducts and vessels. Irreversible electroporation requires very precise needle placement, which has limited its ubiquitous use. Intraprocedural cone-beam computed tomography with navigation can be fused with previous imaging to provide real-time tumor navigation capabilities during the procedure to allow for more accurate needle placement and treatment. Here, we present a patient who underwent percutaneous irreversible electroporation with intraprocedural cone-beam computed tomography fusion guidance to treat his pancreatic cancer. Case presentation The patient, an 88-year-old White male, initially presented with abdominal pain, and was ultimately diagnosed with locally advanced pancreatic cancer. He has an excellent performance status and no other comorbidities. He was started on chemotherapy and radiation therapy, with good response. However, continued vascular involvement of the tumors precluded him from safe surgical resection. The patient underwent irreversible electroporation with intraprocedural cone-beam computed tomography fusion navigation. The primary lesion demonstrates no residual tumor, and the soft tissue involvement of the adjacent vasculature has stabilized. Conclusions Although not curative on its own, irreversible electroporation holds promise as a treatment option for patients with locally advanced pancreatic cancer to increase downsizing to curative surgery or increase quality of life. Cone-beam computed tomography navigation can improve irreversible electroporation by providing guidance during needle guidance. Image fusion with previous advanced imaging can improve lesion visualization and targeting, thereby improving the effectiveness of irreversible electroporation. Keywords: Locally advanced pancreatic cancer, Irreversible electroporation, Cone-beam computed tomography, Case report
The aim of this study was to assess the rate of self-scheduling and self-referral for screening mammography and to assess sociodemographic factors associated with their use in an academic health care ...system in southern California.
Patients scheduled for screening mammography between February 1, 2021, and September 20, 2022, were included in this retrospective study. Multivariable logistic regression models were used to assess associations among sociodemographic factors, self-referral, and online self-scheduling pathways.
In total, 22,306 patients were scheduled for screening mammography (mean age, 59 years; 66.8% White, 20.4% Asian, and 20.6% Hispanic). Overall, 3,566 (16.0%) used online self-scheduling, and 1,232 (5.5%) self-referred for screening mammography. Patients 70 years or older (versus 50 years or younger) (odds ratio OR, 0.41; 95% confidence interval CI, 0.34-0.51), Spanish (versus English) speakers (OR, 0.22; 95% CI, 0.16-0.31), and those on Medicaid (versus commercially insured) (OR, 0.71; 95% CI, 0.50-0.99) were less likely to self-schedule. Hispanic patients (versus non-Hispanic) (OR, 1.39; 95% CI, 1.20-1.61), Asian patients (versus White) (OR, 1.64; 95% CI, 1.46-1.85), and patients residing in the most (versus least) disadvantaged neighborhoods (OR, 1.16; 95% CI, 1.02-1.33) were more likely to self-schedule. Furthermore, patients 70 years or older (versus 50 or younger) (OR, 0.70; 95% CI, 0.52-0.93) and Spanish speakers (OR, 0.05; 95% CI, 0.03-0.09) were less likely to self-refer, whereas Black patients (versus White) (OR, 1.89; 95% CI, 1.30-2.75), patients on Medicaid (versus commercially insured) (OR, 3.70; 95% CI, 2.65-5.13), and patients living in the most (versus least) disadvantaged neighborhoods (OR, 1.52; 95% CI, 1.27-1.82) were more likely to self-refer.
Sociodemographic differences in online patient portal use and self-referral for screening mammography suggest that the two pathways have been successful in addressing some of the existing scheduling barriers and are a step toward closing the disparity gap.
The Arabian horse, one of the world's oldest breeds of any domesticated animal, is characterized by natural beauty, graceful movement, athletic endurance, and, as a result of its development in the ...arid Middle East, the ability to thrive in a hot, dry environment. Here we studied 378 Arabian horses from 12 countries using equine single nucleotide polymorphism (SNP) arrays and whole-genome re-sequencing to examine hypotheses about genomic diversity, population structure, and the relationship of the Arabian to other horse breeds. We identified a high degree of genetic variation and complex ancestry in Arabian horses from the Middle East region. Also, contrary to popular belief, we could detect no significant genomic contribution of the Arabian breed to the Thoroughbred racehorse, including Y chromosome ancestry. However, we found strong evidence for recent interbreeding of Thoroughbreds with Arabians used for flat-racing competitions. Genetic signatures suggestive of selective sweeps across the Arabian breed contain candidate genes for combating oxidative damage during exercise, and within the "Straight Egyptian" subgroup, for facial morphology. Overall, our data support an origin of the Arabian horse in the Middle East, no evidence for reduced global genetic diversity across the breed, and unique genetic adaptations for both physiology and conformation.
In this investigation, a new model for dry fretting wear of similar materials in Hertzian contact is proposed. The wear law which is dependent on material properties, applied load and sliding ...distance is proposed for similar materials under dry fretting wear conditions. Based on this law, a stress based damage mechanics equation for wear is formulated and a finite element model is developed to determine wear rates and wear coefficients. The modeling approach proposed is based on wear at the level of material microstructure and thus Voronoi tessellation is used to configure the microstructure of the bodies in contact. To simulate fretting wear, fatigue crack initiation and propagation along the grain boundaries, and grain removal technique is developed. Two distinct regions – wear initiation and wear propagation are observed from the results of the simulation. The results of the simulation are compared with the Archard wear law and the calculated wear coefficients are of the same order as suggested in the literature. Wear volume measurements for partial slip regime in fretting wear are obtained using the model and the effects of coefficient of friction, hardness and Young's modulus on fretting wear is studied. It is found that the wear rate is significantly influenced by hardness and Young's modulus while the applied coefficient of friction has little to no effect on the wear rate. A regression analysis of the results and a wear map technique to predict wear rates based on material parameters is also presented.
•Dry fretting wear (partial slip regime) of similar materials in Hertzian contact is modeled.•A wear law independent of experimental constants is proposed.•Damage mechanics is used to simulate crack propagation and element deletion.•Wear coefficients are calculated and compared to Archard's wear law.•Wear rate depends significantly on Hardness and Young's modulus.
This paper investigates natural convection and entropy generation of the Nano-Encapsulated phase change materials (NEPCMs) in an inclined L-shaped cavity. The NEPCMs are made up of core and shell in ...which the PCMs are the core section that are capsulated in Nano-shells. These NEPCM particles go through phase change from solid to the liquid while absorbing the heat and release it when their phase changes back to solid. The Navier-Stokes equations are solved by Finite Element Method (FEM) to simulate the behavior of NEPCMs under a set of defined boundary conditions. The effect of Rayleigh number (104-106), micro-rotation parameter (0–2), Nano particle's concentration (0.01–0.05), Stefan number (0.1–0.5), and non-dimensional fusion temperature (0.1–0.3) on the Nusselt number and entropy generation of the fluid flow is also analyzed. The results reveal that the Stefan number, micro-rotation parameter, and non-dimensional fusion temperature have a negative impact on NC heat transfer of NEPCMs and reduce the Nuavg up to 25%, 42%, and 15% respectively. Conversely, the nanoparticle concentration enhances the Nuavg up to 36%.
This work presents an improved probabilistic continuum damage mechanics (CDM) finite element (FE) model to simulate the degradation of material as a function of cycle in order to estimate rolling ...contact fatigue (RCF) life of critical tribological components. Traditionally, CDM-FE models consider the shear reversal to be the damage causing stress in RCF; however, in this investigation, the CDM-FE model also considers the octahedral shear stress, the maximum shear stress, the Fatemi-Socie criteria, and the Dang Van multi-axial fatigue parameter as failure criteria. The critical damage material parameters (σr and m) were obtained from open literature torsion fatigue results. Further, to enable a probabilistic CDM-FE model, the critical damage material parameters (σr and m) were described via a distribution as opposed to fixed values. This allows for the variation of a material’s resistance to fatigue that is present in both torsion and rolling contact fatigue to be captured. Forty unique material microstructure models were created using Voronoi tessellations to capture the random pathways for crack growth. RCF simulations were conducted at five contact pressures between 1.0 GPa and 3.4 GPa. Regression analysis between contact pressure and cycles to failure for each of the failure criteria yielded five unique predictive fatigue life equations, one for each failure criteria investigated. These fatigue life equations were then compared to Lundberg-Palmgren theory considering appropriate material and lubrication factors. The results demonstrated that the Fatemi-Socie and shear stress reversal failure criteria compared favorably to Lundberg-Palmgren theory. Notably, the Fatemi-Socie criteria exhibited closer agreement with Lundberg and Palmgren theory at higher contact pressures, in contrast to the shear reversal criteria.
•An improved probabilistic CDM framework investigated RCF failure criteria.•Weibull scatter from improved model better matched Lundberg-Palmgren scatter.•Shear reversal and Fatemi-Socie criteria match well-established RCF theory.•Fatemi-Socie closely aligns with Lundberg-Palmgren at high contact pressures.
Objective
Behçet's disease (BD) is a chronic, relapsing, inflammatory vascular disease with no pathognomonic test. Low sensitivity of the currently applied International Study Group (ISG) clinical ...diagnostic criteria led to their reassessment.
Methods
An International Team for the Revision of the International Criteria for BD (from 27 countries) submitted data from 2556 clinically diagnosed BD patients and 1163 controls with BD‐mimicking diseases or presenting at least one major BD sign. These were randomly divided into training and validation sets. Logistic regression, ‘leave‐one‐country‐out’ cross‐validation and clinical judgement were employed to develop new International Criteria for BD (ICBD) with the training data. Existing and new criteria were tested for their performance in the validation set.
Results
For the ICBD, ocular lesions, oral aphthosis and genital aphthosis are each assigned 2 points, while skin lesions, central nervous system involvement and vascular manifestations 1 point each. The pathergy test, when used, was assigned 1 point. A patient scoring ≥4 points is classified as having BD. In the training set, 93.9% sensitivity and 92.1% specificity were assessed compared with 81.2% sensitivity and 95.9% specificity for the ISG criteria. In the validation set, ICBD demonstrated an unbiased estimate of sensitivity of 94.8% (95% CI: 93.4–95.9%), considerably higher than that of the ISG criteria (85.0%). Specificity (90.5%, 95% CI: 87.9–92.8%) was lower than that of the ISG‐criteria (96.0%), yet still reasonably high. For countries with at least 90%‐of‐cases and controls having a pathergy test, adding 1 point for pathergy test increased the estimate of sensitivity from 95.5% to 98.5%, while barely reducing specificity from 92.1% to 91.6%.
Conclusion
The new proposed criteria derived from multinational data exhibits much improved sensitivity over the ISG criteria while maintaining reasonable specificity. It is proposed that the ICBD criteria to be adopted both as a guide for diagnosis and classification of BD.
Posteriorly migrated disc extrusion may mimic tumoral masses on MRI with contrast; still, this diagnosis must be evoked in patients presenting acute low back pain with a posterior epidural mass. We ...describe a case of epidural posterior migration of an inflammatory lumbar disc herniation in a young patient with acute lumbosciatica. MRI showed an intracanalar mass with intense global enhancement, which is an uncommon feature of this rare condition.
Both ductile iron and steel are widely used to build rolling elements. As ductile irons generally cost less than steels, this study was conducted to evaluate its rolling contact fatigue (RCF) ...performance by comparing with that of the AISI 1080 steel.
The RCF resistance of two ductile iron variants, chilled ductile iron (CDI) and quenched and tempered ductile iron (Q&T DI), was evaluated. RCF testing was performed using a 3-ball and rod rig. The CDI and Q&T DI results were compared to those of Q&T 1080 steel. The three groups of specimens were processed to ensure a consistent surface hardness of 60 HRC prior to testing. Q&T DI exhibits a much lower RCF loading capacity (2.1 GPa) compared with CDI (3.6 GPa). Under the same loading condition, CDI demonstrated a significantly lower RCF resistance compared with Q&T 1080 steel. Failures in CDI was found to be independent of graphite, which explains CDI’s improved RCF life compared to Q&T DI. This improvement is attributed to higher micro-hardness and less variation throughout the material. The microstructure of tested CDI was analyzed with electron backscatter diffraction (EBSD) from the specimen surface to the core. These observations on carbide volume fraction and growth preference correlated to cooling rate differences between the material groups. This study paves the way for mechanistically based process design of ductile iron variants to achieve comparable RCF life of steels.
•Similar surface hardness in the range 57.3–60.4HRC were achieved with three materials.•Quenched and tempered 1080 steel outperformed cast irons in rolling contact fatigue.•Chilled ductile outperformed quenched and tempered ductile iron even with lower surface hardness.•Improved microstructure consistency was found to benefit fatigue life of cast irons.•RCF performance of iron may be further improved by optimization of microconstituent volume and morphology.
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