Multilayered nanoplasmonic arrays for self-referenced biosensing

Nanostructured sensors based on localized surface plasmon resonance (LSPR) offer a number of advantages over other optical sensing technologies, making them excellent candidates for miniaturized, label-free chemical and biological detection. Highly sensitive to local refractive index changes, the resonance peaks of the nanosensors shift by different amounts when subject to different biological and chemical environments. Modifications to the nanostructure surface allow for the detection of specific molecules and chemicals with shifts so sensitive that the presence of single molecules can be detected. However, this extreme sensitivity has its drawbacks. Resonance shifts also occur because of temperature shifts, light-intensity fluctuations, and other environmental factors. To distinguish detection from drift, a secondary sensor region is often required. This often doubles the size of the device, requires two light sources and detectors (or complex optics), doubles the sample volume required (which may be expensive, or may not be possible if the sample quantity is limited), and subjects the reference to potential biofouling. Here, we present a new proof-of-concept multilayered LSPR sensor design that incorporates both a sensing layer and an encapsulated reference layer within the same region. By doing so, we are able to monitor and correct for sensor drift without the need for a secondary reference channel. We demonstrate the suitability of this sensor for sucrose concentration measurements and for the detection of biotin–avidin interactions, while also showing that the sensor can self-correct for drift. We believe that this multilayer sensor design holds promise for point-of-care diagnostics

Prostate cancer assessment using MR elastography of fresh prostatectomy specimens at 9.4 T

Purpose: Despite its success in the assessment of prostate cancer (PCa), in vivo multiparametric MRI has limitations such as interobserver variability and low specificity. Several MRI methods, among them MR elastography, are currently being discussed as candidates for supplementing conventional multiparametric MRI. This study aims to investigate the detection of PCa in fresh ex vivo human prostatectomy specimens using MR elastography. Methods: Fourteen fresh prostate specimens from men with clinically significant PCa without formalin fixation or prior radiation therapy were examined by MR elastography at 500 Hz immediately after radical prostatectomy in a 9.4T preclinical scanner. Specimens were divided into 12 segments for both calculation of storage modulus (G ' in kilopascals) and pathology (Gleason score) as reference standard. Sensitivity, specificity, and area under the receiver operating characteristic curve were calculated to assess PCa detection. Results: The mean G ' and SD were as follows: all segments, 8.74 ± 5.26 kPa; healthy segments, 5.44 ± 4.40 kPa; and cancerous segments, 10.84 ± 4.65 kPa. The difference between healthy and cancerous segments was significant with P ≤ .001. Diagnostic performance assessed with the Youden index was as follows: sensitivity, 69%; specificity, 79%; area under the curve, 0.81; and cutoff, 10.67 kPa. Conclusion: Our results suggest that prostate MR elastography has the potential to improve diagnostic performance of multiparametric MRI, especially regarding its 2 major limitations: interobserver variability and low specificity. Particularly the high value for specificity in PCa detection is a stimulating result and encourages further investigation of this method

Nanoplasmonic discrimination of organic solvents using a bimetallic optical tongue

Optical sensor arrays serve as excellent tools for the recognition and discrimination of a variety of liquid and gas mixtures. They achieve this via pattern-based recognition from signals across multiple sensing regions, where each region is modified to produce a different interaction, such as partial-selectivity, with desired analytes. As their use progresses towards rapid, highly personalized diagnosis and component identification devices, reduction in complexity and data-acquisition time is key. One way to achieve this is through reducing the number of elements in the array without compromising the differential capabilities of the device. Here, we present a device with elements consisting of plasmonic sensors of two superimposed plasmonic nanoarrays; one fabricated using gold and the other aluminum. Each material produces a distinct plasmonic response while also allowing us to selectively functionalize each pattern with a different â€sensing chemistry.' This allows for the development of different partially-selective elements, via modification with functional thiols and silanes, respectively. Since optical sensing arrays of this type require multiple sensing regions, each producing a different optical response, our bimetallic method results in twice as much data from one measurement, providing the same amount of data necessary to allow for successful differentiation with fewer elements in the sensing array. We demonstrate that by altering the surface chemistry of the nanostructures we can tune their partial selectivity to organic solvents. We believe this technology could be useful in areas that rely on assays for simultaneous determination of multiple analytes, such as the medical, food and drug, and security industries

Submacular Choroid Thickness Increases During Long-Duration Spaceflight

The Spaceflight Associated Neuro-ocular Syndrome (SANS) is characterized by the development of optic disc edema, choroidal folds, cotton-wool spots, globe flattening, and/or refractive error changes greater than or equal to 0.75D during long-duration spaceflight to the International Space Station (ISS). It is hypothesized that these findings result from the headward fluid shift that occurs due to weightlessness. We can induce a headward fluid shift on Earth using positional changes and on ISS due to weightlessness. Lower-body negative pressure (LBNP) is used to reverse the headward fluid shift by drawing fluid into the lower body and can be used on Earth and on ISS

Comparison of baricitinib, upadacitinib, and tofacitinib mediated regulation of cytokine signaling in human leukocyte subpopulations

BACKGROUND: The in vitro pharmacology of baricitinib, upadacitinib, and tofacitinib was evaluated to understand differences among these JAK inhibitors (JAKis) at the cellular level. METHODS: Peripheral blood mononuclear cells from healthy donors were incubated with different JAKis, levels of phosphorylated signal transducer and activator of transcription (pSTAT) were measured following cytokine stimulation, and half maximum inhibitory concentration (IC50) values were calculated in phenotypically gated leukocyte subpopulations. Therapeutic dose relevance of the in vitro analysis was assessed using calculated mean concentration-time profiles over 24 h obtained from JAKi-treated subjects. Time above IC50 and average daily percent inhibition of pSTAT formation were calculated for each JAKi, cytokine, and cell type. RESULTS: Distinct JAKis displayed different in vitro pharmacologic profiles. For example, tofacitinib and upadacitinib were the most potent inhibitors of the JAK1/3-dependent cytokines tested (interleukin [IL]-2, IL-4, IL-15, and IL-21) with lower IC50 values and increased time above IC50 translating to a greater overall inhibition of STAT signaling during the dosing interval. All JAKis tested inhibited JAK1/2-dependent cytokines (e.g., IL-6 and interferon [IFN]-γ), the JAK1/tyrosine kinase 2 (TYK2)-dependent cytokines IL-10 and IFN-α, the JAK2/2-dependent cytokines IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF), and the JAK2/TYK2-dependent cytokine granulocyte colony-stimulating factor (G-CSF), but often to significantly differing degrees. CONCLUSIONS: Different JAKis modulated distinct cytokine pathways to varying degrees, and no agent potently or continuously inhibited an individual cytokine signaling pathway throughout the dosing interval. Notably, baricitinib inhibited JAK1/3 signaling to a lesser extent than upadacitinib and tofacitinib, while upadacitinib, baricitinib, and tofacitinib inhibited the signaling of JAK2/2-dependent cytokines, including GM-CSF and IL-3, as well as the signaling of the JAK2/TYK2-dependent cytokine G-CSF

Evidence Report: Risk of Spaceflight Associated Neuro-ocular Syndrome (SANS)

A subset of astronauts develop neuro-ocular structural and functional changes during prolonged periods of spaceflight that may lead to additional neurologic and ocular consequences upon return to Earth

Association of Inventory to Measure and Assess imaGe Disturbance - Head and Neck Scores With Clinically Meaningful Body Image-Related Distress Among Head and Neck Cancer Survivors

Objective: The Inventory to Measure and Assess imaGe disturbance - Head and Neck (IMAGE-HN) is a validated patient-reported outcome measure of head and neck cancer-related body image-related distress (BID). However, the IMAGE-HN score corresponding to clinically relevant BID is unknown. The study objective is to determine the IMAGE-HN cutoff score that identifies head and neck cancer patients with clinically relevant BID. Methods: We conducted a cross-sectional study at six academic medical centers. Individuals ≥18 years old with a history of head and neck cancer treated with definitive intent were included. The primary outcome measure was the IMAGE-HN. A Receiver Operating Characteristic curve analysis was performed to identify the IMAGE-HN score that maximized sensitivity and specificity relative to a Body Image Scale score of ≥10 (which indicates clinically relevant BID in a general oncology population). To confirm the validity of the IMAGE-HN cutoff score, we compared the severity of depressive [Patient Health Questionnaire-9 (PHQ-9)] and anxiety symptoms [Generalized Anxiety Disorder-7 (GAD-7)], and quality of life [University of Washington-QOL (UW-QOL)] in patients with IMAGE-HN scores above and below the cutoff. Results: Of the 250 patients, 70.4% were male and the mean age was 62.3 years. An IMAGE-HN score of ≥22 was the optimal cutoff score relative to a Body Image Scale score of ≥10 and represents a clinically relevant level of head and neck cancer-related BID. Relative to those with an IMAGE-HN score of \u3c22, patients with IMAGE-HN scores of ≥22 had a clinically meaningful increase in symptoms of depression (mean PHQ-9 score difference = 5.8) and anxiety (mean GAD-7 score difference = 4.1) as well as worse physical (mean UW-QOL score difference = 18.9) and social-emotional QOL (mean UW-QOL score difference = 21.5). Using an IMAGE-HN cutoff score ≥22, 28% of patients had clinically relevant BID. Conclusion: An IMAGE-HN score of ≥22 identifies patients with clinically relevant head and neck cancer-related BID. This score may be used to detect patients who could benefit from strategies to manage their distress, select patients for studies evaluating interventions to manage head and neck cancer-related BID, and improve our understanding of the underlying epidemiology of the disorder

Changes in the Optic Nerve Head and Choroid Over 1 Year of Spaceflight

Importance: While 6-month data are available regarding spaceflight-associated neuro-ocular syndrome, manned missions for 1 year and beyond are planned, warranting evaluation for spaceflight-associated neuro-ocular syndrome beyond 6 months. Objective: To determine if the manifestation of spaceflight-associated neuro-ocular syndrome worsens during International Space Station missions exceeding the present 4- to 6-month duration. Design, Setting, and Participants: The One-Year Mission Study used quantitative imaging modalities to investigate changes in ocular structure in 2 crew members who completed a 1-year-long spaceflight mission. This study investigated the ocular structure of crew members before, during, and after their mission on the International Space Station. Two crew members participated in this study from March 2015 to September 2016. Analysis began in March 2015 and ended in May 2020. Exposures: Crew members were tested before, during, and up to 1 year after spaceflight. Main Outcomes and Measures: This study compares ocular changes (peripapillary retinal edema, axial length, anterior chamber depth, and refraction) in two 1-year spaceflight mission crew members with cohort crew members from a 6-month mission (n = 11). Minimum rim width (the shortest distance between Bruch membrane opening and the internal limiting membrane) and peripapillary total retinal thickness were measured using optical coherence tomography. Results: Both crew members were men. Minimum rim width and total retinal thickness increased in both participants throughout the duration of spaceflight exposure to the maximal observed change from preflight (minimum rim width: participant 1, 561 [+149 from preflight] μm at flight day 270; participant 2, 539 [+56 from preflight] μm at flight day 270; total retinal thickness: participant 1, 547 [+135 from preflight] μm at flight day 90; participant 2, 528 [+45 from preflight] μm at flight day 210). Changes in peripapillary choroid engorgement, axial length, and anterior chamber depth appeared similar between the 1-year mission participants and a 6-month mission cohort. Conclusions and Relevance: This report documents the late development of mild optic disc edema in 1 crew member and the progressive development of choroidal folds and optic disc edema in another crew member over the duration of 1 year in low Earth orbit aboard the International Space Station. Previous reports characterized the ocular risk associated with 4 to 6 months of spaceflight. As future spaceflight missions are planned to increase in duration and extend beyond low Earth orbit, further observation of astronaut ocular health on spaceflight missions longer than 6 months in duration may be warranted

Generalizations of Nonlinear and Supersymmetric Classical Electrodynamics

We first write down a very general description of nonlinear classical electrodynamics, making use of generalized constitutive equations and constitutive tensors. Our approach includes non-Lagrangian as well as Lagrangian theories, allows for electromagnetic fields in the widest possible variety of media (anisotropic, piroelectric, chiral and ferromagnetic), and accommodates the incorporation of nonlocal effects. We formulate electric-magnetic duality in terms of the constitutive tensors. We then propose a supersymmetric version of the general constitutive equations, in a superfield approach.Comment: 15 pages, based on the presentation by G. A. Goldin at QTS