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Abstract Background Primary vitreoretinal lymphoma (PVRL) is an aggressive lymphoma that may present with protean features and represents a diagnostic challenge. Given that patients with PVRL are at high risk of CNS involvement with a high mortality and morbidity rate, prompt diagnosis is crucial to initiate treatment early in the disease course. A multimodality imaging approach including fundus photography, fundus autofluorescence (FAF), optical coherence tomography (OCT), fluorescein and indocyanine angiography, and electroretinography (ERG) can provide information to establish a diagnosis and provide objective measures for management. We review key findings seen via these imaging modalities in patients with PVRL. Observations Fundus photography can highlight commonly seen patterns of PVRL including vitritis, subretinal disease, retinal pigment epithelial (RPE) abnormalities, optic nerve edema, retinal detachment, and less typical retinitis-like lesions. FAF can identify characteristic patterns of hyper- and hypoautofluorescent signal abnormalities in the macula. Spectral-domain OCT will demonstrate vitreous cells, RPE nodularity, and hyperreflectivity of the outer retina. The presence of a hyper-reflective band in the subretinal space and infiltrates between the RPE and Bruch’s membrane can assist in distinguishing PVRL from choroidal lymphoma. Vertical hyperreflective columns (VHRLs) are another pertinent finding that may represent microinfiltrates of the tumor. OCT has proven to be a particularly useful modality in assessing the progress of treatment in PVRL. Fluorescein angiography can show RPE changes, which include granularity, late staining at the RPE level, and blockage. Indocyanine green angiography (ICGA) primarily shows hypocyanescence, which corresponds to PVRL lesions on fundus photography and may occur secondary to loss of RPE and choriocapillaris. Conclusion While PVRL remains a challenging disease to diagnose and follow, the use of a multimodality imaging approach may assist in establishing a diagnosis. Because of the anatomic spaces PVRL may affect, fundus photography, OCT, FAF, angiography, and ERG can identify key characteristics of the disease, differentiate PVRL from other diseases, and provide baseline information for targeted systemic and local therapies. Further assessment of anatomic and functional targets will aid our clinical application of multimodal imaging in the management of PVRL.

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) has infected millions of individuals and continues to be a major health concern worldwide. While reverse transcription-polymerase chain reaction remains a reliable method for detecting infections, limitations of this technology, particularly cost and the requirement of a dedicated laboratory, prevent rapid viral monitoring. Antigen tests filled this need to some extent but with limitations including sensitivity and specificity, particularly against emerging variants of concern. Here, we developed aptamers against the SARS-CoV-2 Nucleocapsid protein to complement or replace antibodies in antigen detection assays. As detection reagents in ELISA-like assays, our DNA aptamers were able to detect as low as 150 pg/mL of the protein and under 150 k copies of inactivated SARS-CoV-2 Wuhan Alpha strain in viral transport medium with little cross-reactivity to other human coronaviruses (HCoVs). Further, our aptamers were reselected against the SARS-CoV-2 Omicron variant of concern, and we found two sequences that had a more than two-fold increase in signal compared to our original aptamers when used as detection reagents against protein from the Omicron strain. These findings illustrate the use of aptamers as promising alternative detection reagents that may translate for use in current tests and our findings validate the method for the reselection of aptamers against emerging viral strains.

OBJECTIVE:Intravitreal melphalan injections are commonly used in the treatment for intraocular retinoblastoma. This study compares retinal toxicity and ocular survival between two formulations, with and without propylene glycol (Alkeran vs. Evomela, respectively). METHODS:A retrospective cohort study of retinoblastoma patients who received intravitreal injections of Alkeran and Evomela at 30 μg from September 2012 to January 2019 at a single tertiary care center were enrolled. Retinal toxicity was measured using electroretinogram (ERG) and compared using a multivariate analysis of 338 injections in 101 eyes of 96 patients. Ocular survival of 163 eyes in 150 patients was compared across formulations using Cox proportional hazards model. Eyes were censored at the time a patient received a dose other than 30 μg. RESULTS:Overall, ERG decline (mean, 95% CI) for each injection was -5.58 μV (-7.17, -3.99). No significant differences in ERG decrement were found between Alkeran (with alcohol) -5.52uV (-6.99, -4.05). and Evomela (without alcohol) -5.65uV (-8.31 to -2.98) formulations (p = 0.93). Ocular survival at 24 months was 93.6% (95% CI 86.2, 97.1) with alcohol and 91.7% (95% CI 53.9, 98.8) without alcohol. The hazard ratio (HR) for without vs with alcohol was 0.50 (95% CI 0.06 to 4.07); no significant difference in ocular survival was found between formulations (p = 0.52). CONCLUSIONS AND RELEVANCE:No differences were found in retinal toxicity and ocular survival between 30 μg intravitreal injections of Alkeran or Evomela for intraocular retinoblastoma. Given the increased stability of Evomela, intravitreal treatment could be expanded to centers without the ability to supply Alkeran due to its shorter safety window; however, Alkeran is less expensive. For those with existing infrastructure, Alkeran is a comparable, cost-effective alternative.

OBJECTIVES/SPECIFIC AIMS: Evidence-based guideline-concordant care leads to better outcomes in patients with early stage breast cancer, including survival. However, previous studies of guideline compliance have been limited by small study sample sizes, localized geography, unknown causal factors, and lack of diverse population. We use a national database to assess socio-economic, clinical, and facility factors that impact treatment compliance with evidence-based guidelines from the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN). METHODS/STUDY POPULATION: This is a retrospective cohort study of the National Cancer Data Base Participant User File Breast 2014, which captures ~70%–80% of all newly diagnosed cancer cases in the United States. Female patients who were diagnosed with early stage breast adenocarcinoma (T0, T1, T1A, T1B, 2, 2A, or T2N1) from 2004 to 2014 were eligible for this study. RESULTS/ANTICIPATED RESULTS: A total of 807,314 patients were included in this study. Evidence-based guidelines examined with associated compliance rates include surgery completion (79.3% overall compliance), breast conserving surgery Versus mastectomy (88.05% vs. 11.95%, respectively), radiation after breast conserving surgery (77.5% overall compliance), HER2 testing (88.6% overall compliance), estrogen/progesterone receptor (ER/PR) testing (96.3% overall compliance), hormone treatment for positive ER/PR breast cancer (80.2% overall compliance), and sentinel lymph node biopsy completion (67.5% overall compliance). Univariate association between these guidelines and covariates such as facility type, facility location, age, race, insurance status, median income quartiles, achievement of high school degree, urban Versus rural, Charlson-Deyo score, year of diagnosis, and overall survival were assessed. Logistic regression analysis will be used to determine multivariate relationships between these characteristics and the probability that a patient will be compliant to guideline regimen. DISCUSSION/SIGNIFICANCE OF IMPACT: The results of this study will help identify socio-economic, clinical, and facility factors that influence guideline-concordant care and subsequent critical outcomes for patients with early stage breast cancer. Lack of guideline concordant care for specific stages of cancer or treatment modalities will point to a need for tailored interventions to enhance compliance. A prediction model will help identify the most important predictors of noncompliance in breast cancer treatment so noncompliance can be prevented in at-risk populations.

We utilize a multifunctional atomic force microscope (AFM) cantilever applying highly localized temperature and electric fields to interrogate transport in single-wall carbon nanotube field-effect transistors (CNTFETs). The probe can be operated either in contact with the CNT, in intermittent contact, or as a Kelvin probe, and can independently control the electric field, mechanical force, and temperature applied to the CNT. We modulate current flow in the CNT with tip-applied electric field, and find this field-effect depends upon both cantilever heating and CNT self-heating. CNT transport is also investigated with AFM tip temperature up to 1170 °C. Tip-CNT thermal resistance is estimated at 1.6 × 107K/W and decreases with increasing temperature. Threshold force (<100 nN) for reliable contact mode imaging is extracted and used to determine set points for nanotube manipulation, such as displacement or cutting. The ability to measure thermal coupling to a single-molecule electronic device could offer new insights into nanoelectronic devices. [ABSTRACT FROM AUTHOR]

We describe a pulsed measurement technique for suppressing hysteresis for carbon nanotube (CNT) device measurements in air, vacuum, and over a wide temperature range (80-453 K). Varying the gate pulse width and duty cycle probes the relaxation times associated with charge trapping near the CNT, found to be up to the 0.1-10 s range. Longer off times between voltage pulses enable consistent, hysteresis-free measurements of CNT mobility. A tunneling front model for charge trapping and relaxation is also described, suggesting trap depths up to 4-8 nm for CNTs on SiO2. Pulsed measurements will also be applicable for other nanoscale devices such as graphene, nanowires, or molecular electronics, and could enable probing trap relaxation times in a variety of material system interfaces. [ABSTRACT FROM AUTHOR]