While exact analytic solutions for space-charge-limited currents (SCLCs) are well-established for parallel plate geometries, they have only recently been derived for concentric cylindrical and ...spherical geometries using variational calculus (VC). However, actual diode systems and slow-wave structures are usually more complicated, making SCLC calculations more difficult. In this article, we apply conformal mapping to derive the analytical solutions for SCLC for various complicated geometries exhibiting curvilinear flow. We first replicate the exact solution of SCLC for concentric cylindrical electrodes from VC using conformal mapping to transform from the Child-Langmuir (CL) law for a planar geometry. We then derive SCLC in other geometries using conformal transformations to either the planar or the concentric cylinder solution. Because the SCLC calculated using such conformal mappings depends only on the CL law, this may permit future incorporation of relativistic or quantum corrections to determine the appropriate relationships for more complicated geometries.
Immune checkpoint inhibitors (ICIs) produce durable responses in some melanoma patients, but many patients derive no clinical benefit, and the molecular underpinnings of such resistance ...remain elusive. Here, we leveraged single-cell RNA sequencing (scRNA-seq) from 33 melanoma tumors and computational analyses to interrogate malignant cell states that promote immune evasion. We identified a resistance program expressed by malignant cells that is associated with T cell exclusion and immune evasion. The program is expressed prior to immunotherapy, characterizes cold niches in situ, and predicts clinical responses to anti-PD-1 therapy in an independent cohort of 112 melanoma patients. CDK4/6-inhibition represses this program in individual malignant cells, induces senescence, and reduces melanoma tumor outgrowth in mouse models in vivo when given in combination with immunotherapy. Our study provides a high-resolution landscape of ICI-resistant cell states, identifies clinically predictive signatures, and suggests new therapeutic strategies to overcome immunotherapy resistance.
Display omitted
•Single-cell RNA-seq identifies an immune resistance program in malignant cells•Multiple immune resistance mechanisms are co-regulated in the program•The program predicts clinical responses to immunotherapy in melanoma patients•CDK4/6 inhibitors repress the program and may sensitize melanoma to immunotherapy
Single-cell sequencing of checkpoint-inhibitor-resistant melanomas identifies predictive signatures to guide therapeutic approaches to overcome immunotherapy resistance.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Surgical exclusion of the left atrial appendage (LAA) can frequently yield incomplete closure.
We evaluated the ischemic stroke/systemic embolization (SSE) risk in patients with atrial fibrillation ...(AF) and complete LAA closure (cLAA) vs incompletely surgically ligated LAA (ISLL) and LAA stump after surgical suture ligation.
Seventy-two patients (CHA2DS2-VASc score 4.1 ± 1.9) underwent surgical LAA ligation in conjunction with mitral valve/AF surgery and postoperative LAA evaluation using computerized tomographic angiography.
Overall, cLAA was detected in 46 of 72 patients (64%), ISLL in 17 patients (24%), and LAA stump in 9 patients (12%). The incidences of oral anticoagulation (OAC) and recurrent AF were similar among the 3 groups during 44 ± 19 months of follow-up. SSE occurred in 2% of patients with cLAA vs 24% with ISLL and 0% with LAA stump (P = .006). None of the patients with SSE were receiving OAC, and all had recurrent AF during follow-up. Additionally, patients with SSE exhibited a significantly smaller ISLL neck diameter (2.8 ± 1.0 vs 7.1 ± 2.1 mm; P = .002). The annualized SSE risk was 1.9% (entire cohort), 6.5% (ISLL patients), 14.4% (ISLL patients not receiving OAC), and 19.0% (ISLL neck diameter ≤5.0 mm) per 100 patient-years of follow-up. The latter risk was nearly 5 times greater than predicted by conventional risk-stratification schemes. Moreover, ISLL emerged as an independent predictor of SSE in univariate analyses and as the sole predictor of SSE in a multivariate analysis.
In patients with AF, ISLL is a predictor of SSE, independent of conventional risk stratification schemes. Consequently, OAC should be strongly considered in this high-risk cohort.
While analytic equations for space-charge limited current density (SCLCD) have been derived for planar and nonplanar geometries, the SCLCD for emission from a sharp tip has not been derived. In this ...article, we use variational calculus (VC) to derive an exact analytic equation for SCLCD for a 1-D tip-to-tip geometry, represented by hyperboloids in the prolate spheroidal coordinates, and recover the SCLCD for a tip-to-plate geometry as a special case. We then consider circles in the extended Poincaré disk, which is the stereographic projection of hyperboloids onto a plane, as conformal transformations to derive the SCLCD for a misaligned tip-to-tip geometry, where the axes of rotation of the hyperboloids are displaced by a small distance. This mapping technique is also applied to study the effect of a small angle tilt in a tilted tip-to-tip geometry, where the axes of rotation of the hyperboloids meet at an angle.
Elemental mapping using energy-dispersive x-ray spectroscopy in scanning transmission electron microscopy, a well-established technique for precision elemental concentration analysis at submicron ...resolution, was first demonstrated at atomic resolution in 2010. However, to date atomic resolution elemental maps have only been interpreted qualitatively because the elastic and thermal scattering of the electron probe confounds quantitative analysis. Accounting for this scattering, we present absolute scale quantitative comparisons between experiment and quantum mechanical calculations for both energy dispersive x-ray and electron energy-loss spectroscopy using off-axis reference measurements. The relative merits of removing the scattering effects from the experimental data against comparison with direct simulations are explored.
Full text
Available for:
CMK, CTK, FMFMET, IJS, NUK, PNG, UM
Caring for a growing aging population using existing long-term care resources while simultaneously supporting and educating family caregivers, is a public health challenge. We describe the ...application of the Replicating Effective Programs (REP) framework, developed by the Centers for Disease Control Prevention and used in public health program implementation, to scale up an evidence-based family caregiver training intervention in the Veterans Affairs (VA) healthcare system.
From 2018 to 2020, clinicians at eight VA medical centers received REP-guided implementation including facilitation, technical assistance, and implementation tools to deliver the training program. The project team used the REP framework to develop activities across four distinct phases - (1) pre-conditions, (2) pre-implementation, (3) implementation, and (4) maintenance and evolution - and systematically tracked implementation facilitators, barriers, and adaptations.
Within the REP framework, results describe how each medical center adapted implementation approaches to fit local needs. We highlight examples of how sites balanced adaptations and intervention fidelity.
The REP framework shows promise for national expansion of the caregiver training intervention, including to non-VA systems of care, because it allows sites to adapt while maintaining intervention fidelity.
NCT03474380 . Date registered: March 22, 2018.
Full text
Available for:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This study introduces a new automated system that blends multi-satellite information and citizen science data for reliable and timely observations of lake and river ice in under-observed northern ...regions. The system leverages the Google Earth Engine resources to facilitate the analysis and visualization of ice conditions. The adopted approach utilizes a combination of moderate and high-resolution optical data, along with radar observations. The results demonstrate the system’s capability to accurately detect and monitor river ice, particularly during key periods, such as the freeze-up and the breakup. The integration citizen science data showed added values in the validation of remote sensing products, as well as filling gaps whenever satellite observations cannot be collected due to cloud obstruction. Moreover, it was shown that citizen science data can be converted to valuable quantitative information, such as the case of ice thickness, which is very useful when combined with ice extent derived from remote sensing. In this study, citizen science data were employed for the quantitative assessment of the remote sensing product. Obtained results showed a good agreement between the product and observed river status, with a Critical Success Index of 0.82. Notably, the system has shown effectiveness in capturing the spatial and temporal evolution of snow and ice conditions, as evidenced by its application in analyzing specific ice jam events in 2023. The study concludes that the developed system marks a significant advancement in river ice monitoring, combining technological innovation with community engagement.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
PDF
