Hand and finger, ultrasound-guided, percutaneous core needle biopsies: A safe procedure with high diagnostic accuracy.

Introduction/Purpose: To determine the diagnostic accuracy and complication rates of ultrasound-guided, percutaneous core needle biopsies of soft tissue masses in the hand and fingers. Methods: Reports from all ultrasound-guided procedures between 21 May 2014 and 17 March 2022 were queried for keywords including "hand", OR "finger", AND "biopsy". Patient demographics, lesion size and location, biopsy needle gauge and the number of cores obtained were recorded. The final pathology of the mass excision was then compared with the core needle biopsy (CNB) for each patient. Results: Sixty-six records were reviewed, and 37 patients met inclusion criteria. Maximum lesion diameter averaged 1.45 cm with a range between 0.4 and 4.3 cm. The frequency of needle gauges used was 14G (14%), 16G (24%), 18G (38%), 20G (11%) and 'not reported' (14%). The mean number of tissue cores obtained was 2.9 (SD 1.2; range 1 to 6), excluding nine cases that reported 'multiple'. The frequency of CNB diagnoses included tenosynovial giant cell tumour (TGCT) at 30%, ganglion cyst at 11% and epidermal inclusion cyst at 5%. CNB was 100% sensitive in detecting the three (8%) malignancies. Of the 37 tumours biopsied, 16 were surgically excised. One angiomyoma was originally diagnosed as a haemangioma on CNB, but all other histologic results were concordant for a diagnostic accuracy of 97%. Discussion: Small soft tissue masses in the hands and fingers, even those less than 1 cm, are often amenable to ultrasound-guided CNB. Performance under image guidance facilitates retrieval of core specimens adquate for histologic diagnosis with relatively few passes using higher gauge needles. Conclusion: Overall, ultrasound-guided CNB of the hand and fingers is safe and highly accurate in diagnosing soft tissue tumours. The accuracy is unrelated to the needle's gauge, the number of passes and the size of the lesions.

Tamper performance for confined laser drive applications.

The shock imparted by a laser beam striking a metal surface can be increased by the presence of an optically transparent tamper plate bonded to the surface. We explore the shock produced in an aluminum slab, for a selection of tamper materials and drive conditions. The experiments are conducted with a single-pulse laser of maximum fluence up to 100 J/cm2. The pressure and impulse are measured by photon doppler velocimetry, while plasma imaging is used to provide evidence of nonlinear tamper absorption. We demonstrate a pressure enhancement of 50x using simple commercially available optics. We compare results from hard dielectric glasses such as fused silica to soft plastics such as teflon tape. We discuss the mechanism of pressure saturation observed at high pulse fluence, along with some implications regarding applications. Below saturation, overall dependencies on pulse intensity and material parameters such as mechanical impedances are shown to correlate with a model by Fabbro et al.

The Influence of Nonlocal Metal-Dielectric Environments on Physical and Chemical Processes.

ConspectusPlasmonic nanolayers and laminar metallic/dielectric multilayers were originally developed for optical cloaking applications and lensing applications that could potentially image objects whose size was below the diffraction limit. These assemblies were initially formed from gold or silver nanorods grown within an alumina mesh. However, more recently, assemblies with similar properties have also been prepared by sequential thin-layer deposition of alternating layers of gold and magnesium fluoride (MgF2). These metal/dielectric composite materials enable control of the dielectric constant in the directions perpendicular to the layers and balance the real and imaginary dielectric constants of the assembly such that the speed and the amplitude of the waves traveling through the assembly are not attenuated.In this Account, we will also focus on a few of the applications ranging from surface wetting to fluorescence quenching to enhancement of photochemical reactions. First, we will share an introduction to processes used to create these materials, which are combinations of low refractive index metals and transparent higher index materials arranged in a scalable repeating fashion. Two fabrication methods were employed: an electrochemical deposition of Ag nanorods into an anodized alumina matrix which produced materials with an anisotropic negative refractive index material within the plane of the film and lamellar metal/dielectric layers in which the negative index perpendicular to the growth direction. These alternating layers of plasmonic metals and dielectric materials were ultimately chosen to prepare films for further testing, because of their relative ease of fabrication. We will continue with a discussion of a few of the applications of both of these nonlocal dielectric composite materials including more specialized plasmonic, composite, and hyperbolic metamaterials including fluorescence quenching, photochemical reactions, and surface wetting. In each of these applications, the unique response caused by the enhancement of the electric field and the interface between hyperbolic materials and plasmonic materials as they interact photophysically with their near neighbors is presented. In each of the applications, the enhanced electric field extends from the composite substrate layer to interact with its near neighbors and beyond. The presence of this extended interaction can be observed in the form of decreased emission lifetime, enhancement of photochemical reaction rates, and changes in the surface energies measured by contact angle goniometry. In this Account, all of these situations will be addressed. Finally, we will conclude with a summary and vision for the future as well as a discussion of the unique challenges and opportunities available as research active faculty at an HBCU.

Clinical characteristics and postoperative complications as predictors of radiation toxicity after treatment with I125 Eye Plaque Brachytherapy for Uveal Melanomas.

PURPOSE: I125 Eye Plaque brachytherapy is the standard treatment for medium-sized uveal melanomas (UM). Patients develop radiation toxicities (RTT), including radiation maculopathy (RM), radiation neovascular glaucoma/iris neovascularization (RNGI) and radiation optic neuropathy (RON). We aim to investigate demographics, pretreatment tumor characteristics and posttreatment complications as predictors of RTT. METHODS AND MATERIALS: An IRB-approved single-institution retrospective chart review was performed from 2011 to 2019 for patients with posterior UM treated with brachytherapy. We collected demographics, pretreatment tumor characteristics and posttreatment complications. Univariate analysis (UVA) and multivariate analysis (MVA) were performed using logistic regression model. Hazard ratios (HR) and corresponding p-values were reported. All tests were two-sided; statistical significance was considered when p<0.05. RESULTS: Two hundred and fifty eight patients were evaluated. Median follow-up was 33.50 months (range 3.02-97.31). 178 patients (69.0%) had RTT. 131 patients (50.8%) developed RM. Fifty-six patients (21.7%) developed RON. Nineteen patients (7.4%) developed RNGI. UVA found shorter distance to fovea (DF) (p = 0.04), posttreatment exudative retinal detachment (PERD) (p = 0.001) and posttreatment vitreous hemorrhage (PVH) (p = 0.001) are associated with RTT. MVA found shorter DF (HR=1.03, p = 0.04), PERD (HR=2.52, p = 0.01) and PVH (HR=3.34, p = 0.006) are associated with RTT. MVA found female sex (HR=1.731, p = 0.031) and tumor height (HR=1.13, p = 0.013) are associated with RM and pretreatment retinal detachment (HR=3.41, p<0.001) is associated with RON. CONCLUSIONS: Shorter DF, PERD and PVH are associated with RTT; female sex and tumor height are associated with RM and tumor height is associated with RON. These findings serve as prognostic tools to counsel patients and promote early intervention in management of RTT.

Predictors of Local Recurrence and Progression-Free Survival in Iodine-125 Brachytherapy-Treated Uveal Melanomas: A Modern Institutional Study.

Introduction: Iodine-125 brachytherapy is an effective eye-sparing treatment for uveal melanoma. Previous work has shown that uveal melanomas cluster into distinct molecular classes based on gene expression profiles - discriminating low-grade from high-grade tumors. Our objective was to identify clinical and molecular predictors of local recurrence (LR) and progression-free survival (PFS). Methods: We constructed a retrospective database of uveal melanoma patients from the University of Miami's electronic medical records that were treated between January 8, 2012, and January 5, 2019, with either COMS-style or Eye Physics plaque. Data on tumor characteristics, pretreatment retinal complications, post-plaque treatments, LR, and PFS were collected. Univariate and multivariate Cox models for cumulative incidence of LR and PFS were conducted using SAS version 9.4. Results: We identified 262 patients, with a median follow-up time of 33.5 months. Nineteen patients (7.3%) had LR, and 56 patients (21.4%) were classified as PFS. We found that ocular melanocytosis (hazard ratio = 5.55, p < 0.001) had the greatest impact on PFS. Genetic expression profile did not predict LR outcomes (hazard ratio = 0.51, p = 0.297). Conclusion: These findings help physicians identify predictors for short-term brachytherapy outcomes, allowing better shared decision making with patients preoperatively when deciding between brachytherapy versus enucleation. Patients stratified to higher risk groups based on preoperative characteristics such as ocular melanocytosis should be monitored more closely. Future studies must validate these findings using a prospective cohort study.

A phase II trial of durvalumab and tremelimumab in metastatic, non-urothelial carcinoma of the urinary tract.

BACKGROUND: Immune checkpoint blockade has made a significant impact on the clinical outcomes of patients with metastatic urothelial carcinoma (UC). However, evidence for this approach in patients with non-UC of the urinary tract is limited. METHODS: This was a phase II open-label study of durvalumab 1500 mg and tremelimumab 75 mg every 4 weeks for four cycles followed by durvalumab 1500 mg every 4 weeks. Eligible patients had metastatic non-UC with ECOG PS 0-1 regardless of prior therapy (except small cell carcinoma who were pretreated). The primary endpoint was overall response rate per RECIST v1.1. A Simon's minimax two-stage design was employed, with 13 patients planned for stage one. Pre-treatment tumors underwent PD-L1 staining and next-generation sequencing. RESULTS: Thirteen patients were treated, including seven small cell carcinoma, three squamous cell carcinoma, and three adenocarcinoma. Eleven patients had visceral metastases. No responses were observed; 11 patients had PD and 2 patients had SD. Median PFS was 1.8 months (95% CI, 1.25-not reached [NR]) with a median follow-up of 7.38 months (range, 5.23-21.99 months). Median OS was 6.97 months (95% CI, 4.34-NR). One patient's tumor was PD-L1 positive and all sequenced tumors (n = 8) were microsatellite stable. Grades 3-4 treatment-related adverse events occurred in 38.4% of patients. CONCLUSIONS: In a poor prognosis cohort of patients with non-UC, durvalumab and tremelimumab lacked clinical activity while demonstrating a manageable safety profile.

Solvation Properties of Silver and Copper Ions in a Room Temperature Ionic Liquid: A First-Principles Study.

Understanding the behavior of metal ions in room temperature ionic liquids (ILs) is essential for predicting and optimizing performance for technologies like metal electrodeposition; however, many mechanistic details remain enigmatic, including the solvation properties of the ions in ILs and how they are governed by the intrinsic interaction between the ions and the liquid species. Here, we utilize first-principles molecular dynamics simulations to unravel and compare the key structural properties of Ag+ and Cu+ ions in a common room temperature IL, 1-ethyl-3-methylimidazolium trifluoromethanesulfonate. We find that, when compared to Cu+, the larger Ag+ shows a more disordered and flexible solvation structure with a more frequent exchange of the IL species between its solvation shells. In addition, our simulations reveal an interesting analog in the solvation behavior of the ions in the IL and aqueous environments, particularly in the effect of the ion electronic structures on their solvation properties. This work provides fundamental understanding of the intrinsic properties of the metal ions in the IL, while offering mechanistic understanding and strategy for future selection of ILs for metal electrodeposition processes.

Expanding STEM opportunities through inclusive STEM-focused high schools.

Inclusive STEM high schools (ISHSs) (where STEM is science, technology, engineering, and mathematics) admit students on the basis of interest rather than competitive examination. This study examines the central assumption behind these schools-that they provide students from subgroups underrepresented in STEM with experiences that equip them academically and attitudinally to enter and stay in the STEM pipeline. Hierarchical modeling was applied to data from student surveys and state longitudinal data records for 5113 students graduating from 39 ISHSs and 22 comprehensive high schools in North Carolina and Texas. Compared to peers from the same demographic group with similar Grade 8 achievement levels, underrepresented minority and female ISHS students in both states were more likely to undertake advanced STEM coursework. Hispanics in Texas and females in both states expressed more STEM career interest in Grade 12 if they attended an ISHS. Positive relationships between ISHS attendance and grade point average were found in the total sample and each subgroup in North Carolina. Positive ISHS advantages in terms of test scores for the total student sample were found for science in both states and for mathematics in Texas. For the various student subgroups, test score differences favored the ISHS samples but attained statistical significance only for African Americans' science achievement scores in the Texas study.

High content analysis of phagocytic activity and cell morphology with PuntoMorph.

BACKGROUND: Phagocytosis is essential for maintenance of normal homeostasis and healthy tissue. As such, it is a therapeutic target for a wide range of clinical applications. The development of phenotypic screens targeting phagocytosis has lagged behind, however, due to the difficulties associated with image-based quantification of phagocytic activity. NEW METHOD: We present a robust algorithm and cell-based assay system for high content analysis of phagocytic activity. The method utilizes fluorescently labeled beads as a phagocytic substrate with defined physical properties. The algorithm employs statistical modeling to determine the mean fluorescence of individual beads within each image, and uses the information to conduct an accurate count of phagocytosed beads. In addition, the algorithm conducts detailed and sophisticated analysis of cellular morphology, making it a standalone tool for high content screening. RESULTS: We tested our assay system using microglial cultures. Our results recapitulated previous findings on the effects of microglial stimulation on cell morphology and phagocytic activity. Moreover, our cell-level analysis revealed that the two phenotypes associated with microglial activation, specifically cell body hypertrophy and increased phagocytic activity, are not highly correlated. This novel finding suggests the two phenotypes may be under the control of distinct signaling pathways. COMPARISON WITH EXISTING METHODS: We demonstrate that our assay system outperforms preexisting methods for quantifying phagocytic activity in multiple dimensions including speed, accuracy, and resolution. CONCLUSIONS: We provide a framework to facilitate the development of high content assays suitable for drug screening. For convenience, we implemented our algorithm in a standalone software package, PuntoMorph.

Assessment of modulated cytostatic drug resistance by automated γH2AX analysis.

The efficacy of many chemotherapeutic agents relies on the preferential destruction of rapidly dividing cancer cells by inducing various kinds of DNA damage. The most deleterious type of DNA lesions are DNA double-strand breaks (DSB), which can be detected by immunofluorescence staining of phosphorylated histone protein H2AX (γH2AX). Furthermore, γH2AX has been suggested as clinical pharmacodynamic biomarker in chemotherapeutic cancer treatment. A great challenge in treating neoplastic diseases is the varying response behavior among cancer patients. Thus, intrinsic or drug-induced overexpression of efflux pumps often leads to multiple drug resistance (MDR) and treatment failure. In particular, inter-individual differences in expression levels of efflux pumps, such as the permeability glycoprotein (P-gp), were shown to correlate with cancer progression. Several efficient cytostatic drugs, including the DSB-inducing agent etoposide (ETP) are known P-gp substrates. In this respect, modulation of MDR by P-gp inhibitors, like the immunosuppressives cyclosporine A (CsA) and rapamycin (Rapa) have been described. Here, we investigated the application of γH2AX focus assay to monitor the impact of CsA and Rapa on ETP-induced cytotoxicity in human peripheral blood mononuclear cells. Evaluation of γH2AX foci was performed by the automated fluorescence microscopy and interpretation system AKLIDES. Compared to ETP treatment alone, our results revealed a significant rise in γH2AX focus number and percentage of DSB-positive cells after cells have been treated with ETP in the presence of either CsA or Rapa. In contrast, DSB levels of cells incubated with CsA or Rapa alone were comparable to focus number of untreated cells. Our results successfully demonstrated how automated γH2AX analysis can be used as fast and reliable approach to monitor drug resistance and the impact of MDR modulators during treatment with DSB-inducing cytostatics..

Fully automated analysis of chemically induced γH2AX foci in human peripheral blood mononuclear cells by indirect immunofluorescence.

Analysis of phosphorylated histone protein H2AX (γH2AX) foci is currently the most sensitive method to detect DNA double-strand breaks (DSB). This protein modification has the potential to become an individual biomarker of cellular stress, especially in the diagnosis and monitoring of neoplastic diseases. To make γH2AX foci analysis available as a routine screening method, different software approaches for automated immunofluorescence pattern evaluation have recently been developed. In this study, we used novel pattern recognition algorithms on the AKLIDES® platform to automatically analyze immunofluorescence images of γH2AX foci and compared the results with visual assessments. Dose- and time-dependent γH2AX foci formation was investigated in human peripheral blood mononuclear cells (PBMCs) treated with the chemotherapeutic drug etoposide (ETP). Moreover, the AKLIDES system was used to analyze the impact of different immunomodulatory reagents on γH2AX foci formation in PBMCs. Apart from γH2AX foci counting the use of novel pattern recognition algorithms allowed the measurement of their fluorescence intensity and size, as well as the analysis of overlapping γH2AX foci. The comparison of automated and manual foci quantification showed overall a good correlation. After ETP exposure, a clear dose-dependent increase of γH2AX foci formation was evident using the AKLIDES as well as Western blot analysis. Kinetic experiments on PBMCs incubated with 5 µM ETP demonstrated a peak in γH2AX foci formation after 4 to 8 h, while a removal of ETP resulted in a strong reduction of γH2AX foci after 1 to 4 h. In summary, this study demonstrated that the AKLIDES system can be used as an efficient automatic screening tool for γH2AX foci analysis by providing new evaluation features and facilitating the identification of drugs which induce or modulate DNA damage.

IL-1 receptor 2 (IL-1R2) and its role in immune regulation.

The cytokine IL-1 is critical to the pathogenesis of a variety of human conditions and diseases. Unlike most other cytokines, IL-1 is counterbalanced by two endogenous inhibitors. The functional significance of IL-1 receptor antagonist (IL-1RA) is well documented due to the clinical utilization of the recombinant human IL-1RA analog, anakinra. In contrast, much less is known about the type 2 IL-1 receptor (IL-1R2), which acts as a decoy receptor for IL-1. While IL-1R2 is structurally similar to the type 1 IL-1 receptor (IL-1R1) responsible for IL-1 signal transduction, its truncated cytoplasmic domain and lack of Toll-IL-1 receptor (TIR) region renders IL-1R2 incapable of transmembrane signaling. IL-1R2 competes with IL-1R1 for ligands and for the IL-1R1 co-receptor, IL-1 receptor accessory protein (IL-1RAP). Additionally, IL-1R2 exists in both a membrane bound and soluble form (sIL-1R2) that has biological properties similar to both a decoy receptor and a binding protein. Thus far, IL-1R2 has been implicated in arthritis, endometriosis, organ transplantation, sepsis/sickness behavior, diabetes, atherosclerosis, autoimmune inner ear disease (AIED), Alzheimer's disease and ulcerative colitis. In this review, we will detail the functional properties of IL-1R2 and examine its role in human disease.

New platform technology for comprehensive serological diagnostics of autoimmune diseases.

Antibody assessment is an essential part in the serological diagnosis of autoimmune diseases. However, different diagnostic strategies have been proposed for the work up of sera in particular from patients with systemic autoimmune rheumatic disease (SARD). In general, screening for SARD-associated antibodies by indirect immunofluorescence (IIF) is followed by confirmatory testing covering different assay techniques. Due to lacking automation, standardization, modern data management, and human bias in IIF screening, this two-stage approach has recently been challenged by multiplex techniques particularly in laboratories with high workload. However, detection of antinuclear antibodies by IIF is still recommended to be the gold standard method for antibody screening in sera from patients with suspected SARD. To address the limitations of IIF and to meet the demand for cost-efficient autoantibody screening, automated IIF methods employing novel pattern recognition algorithms for image analysis have been introduced recently. In this respect, the AKLIDES technology has been the first commercially available platform for automated interpretation of cell-based IIF testing and provides multiplexing by addressable microbead immunoassays for confirmatory testing. This paper gives an overview of recently published studies demonstrating the advantages of this new technology for SARD serology.