Elastin-like polypeptide delivery of anti-inflammatory peptides to the brain following ischemic stroke.

Inflammatory processes are activated following ischemic stroke that lead to increased tissue damage for weeks following the ischemic insult, but there are no approved therapies that target this inflammation-induced secondary injury. Here, we report that SynB1-ELP-p50i, a novel protein inhibitor of the nuclear factor kappa B (NF-κB) inflammatory cascade bound to the drug carrier elastin-like polypeptide (ELP), decreases NF-κB induced inflammatory cytokine production in cultured macrophages, crosses the plasma membrane and accumulates in the cytoplasm of both neurons and microglia in vitro, and accumulates at the infarct site where the blood-brain barrier (BBB) is compromised following middle cerebral artery occlusion (MCAO) in rats. Additionally, SynB1-ELP-p50i treatment reduces infarct volume by 11.86% compared to saline-treated controls 24 h following MCAO. Longitudinally, SynB1-ELP-p50i treatment improves survival for 14 days following stroke with no effects of toxicity or peripheral organ dysfunction. These results show high potential for ELP-delivered biologics for therapy of ischemic stroke and other central nervous system disorders and further support targeting inflammation in ischemic stroke.

Super Interferometric Range Resolution.

We probe the fundamental underpinnings of range resolution in coherent remote sensing. We use a novel class of self-referential interference functions to show that we can greatly improve upon currently accepted bounds for range resolution. We consider the range resolution problem from the perspective of single-parameter estimation of amplitude versus the traditional temporally resolved paradigm. We define two figures of merit: (i) the minimum resolvable distance between two depths and (ii) for temporally subresolved peaks, the depth resolution between the objects. We experimentally demonstrate that our system can resolve two depths greater than 100× the inverse bandwidth and measure the distance between two objects to approximately 20 µm (35 000 times smaller than the Rayleigh-resolved limit) for temporally subresolved objects using frequencies less than 120 MHz radio waves.

Increasing number and shifting demographics of adolescent opioid use disorder presentations to the emergency department.

INTRODUCTION: Opioid use has been increasing in adolescents; however, lacking are data describing sex, ethnicity, and age groups most affected. We identified and characterized the trend in the adolescent population who presented to the emergency departments (ED) of a large hospital system. METHODS: We obtained data directly from the electronic medical record for patients aged 12-21 years from January 2014 to December 2022. We identified opioid-related visits by primary diagnosis. Trends were compared amongst age groups and by sex and reported ethnicity. RESULTS: Opioid-related presentations increased in all age groups and were significantly increased in adolescents aged 13-17 years compared to patients aged 18-21 years (1700% [range: 1000-3300%] v 400% [200-800%]; p = 0.02). Adolescents presenting to the ED with opioid-related primary diagnoses were more likely to be Hispanic and male in our region. DISCUSSION: Over the last two years (2021-22) there was a significant increase in opioid-related presentations to our hospital system amongst adolescents and an acceleration post-COVID. In 2022, emergency department presentations shifted to younger teenagers and from white young adults to Hispanic adolescents. The increased number of cases posed management problems in the ED given the lack of outpatient treatment options. CONCLUSION: Opioid-related ED presentations are increasing in adolescents with post-COVID increases in male, Hispanic, and younger patients in our region. Pathways for outpatient treatment need to be developed for adolescents with OUD.

Expediting Treatment of Trauma Patients in the Emergency Department: Rapid Trauma Evaluation (RTE).

BACKGROUND: Criteria for trauma determination evolves. We developed/evaluated a Rapid Trauma Evaluation (RTE) process for a trauma patient subset not meeting preestablished trauma criteria. METHODS: Retrospective study (July 2019 - May 2020) for patients either > 65 years with ground level fall within 24 hours or in a motorcycle collision (MCC) arriving by EMS not meeting ACS trauma-criteria. RTE process was immediate evaluation by nurse/EMT, room placement, physician notification, undressing/gowning, vital signs, head-to-toe assessment, upgrade trauma status. Number/type of admissions, discharges, trauma upgrades, LOS obtained via trauma-registry and chart-review. For comparison, historic controls (HC) were used [all patients meeting RTE criteria seen in the ED prior to RTE (Apr- June 2019)]. RESULTS: The RTE cohort (n=755) was 77% falls,23% MCCs, median age 82 [IQR 74-88] years; 42% male-Among falls, 3.2% required a modified-upgrade; 0.7% full-upgrade, 55% admitted [29.4% trauma). HC (n=575) was 92.3% falls, 7.7% MCCs, median age 81 (IQR: 67-88) years, 40.5% males-57.4% admitted (22% trauma). RTE MCC median age 42 (IQR:30-49) years, 84.4% male- 21.9% were upgraded [(6 modified-trauma; 1 full-trauma; 43.8% admitted (85.7% trauma)]. HC MCC median age 29 (IQR: 23-41) years, 95.5% male, 54.5% admitted (75% trauma]. No difference on demographics, admissions or discharges between groups (P>0.05) except HC MCC was younger (P<0.005). RTE median LOS was shorter than HC [203 (IQR: 147-278) minutes vs. 286 (IQR: 205-392) minutes, P<0.001]. CONCLUSIONS: Patients > 65 years with a ground level fall or in a MCC arriving via EMS not meeting ACS trauma criteria may benefit from RTE.

Doppler Gyroscopes: Frequency vs Phase Estimation.

We consider the fundamental roles of frequency versus phase in parameter estimation, specifically in the Sagnac effect. We describe a novel, ultrasensitive gyroscope based on the extremely steep frequency-dependent gain of a liquid crystal light valve. We provide compelling experimental evidence that the Doppler shift is fundamental in the Sagnac effect giving clarity to a long-debated question. We experimentally show orders of magnitude improvement in sensitivity relative to the standard quantum limit of a gyroscope based on phase estimation.

Patient familiarity with, understanding of, and preferences for clinical trial endpoints and terminology.

BACKGROUND: Although there is increased attention to designing and explaining clinical trials in ways that are clinically meaningful for patients, there is limited information on patient preferences, understanding, and perceptions of this content. METHODS: Maximum difference scaling (MaxDiff) methodology was used to develop a survey for assessing patients' understanding of 19 clinical terms and perceived importance of 9 endpoint surrogate phrases used in clinical trials and consent forms. The survey was administered electronically to individuals with metastatic breast cancer affiliated with the Metastatic Breast Cancer Alliance. Analyses were performed using Bayesian P values with statistical software. RESULTS: Among 503 respondents, 77% had a college degree, 70% were diagnosed with metastatic disease ≥2 years before survey completion, and 77% had received ≥2 lines of systemic therapy. Less than 35% of respondents reported understanding "fairly well" the terms symptomatic progression, duration of disease control, time to treatment cessation, and endpoints. Income level and time since onset of metastatic disease correlated with comprehension. Patients who had received ≥6 lines of therapy perceived that time until serious side effects (P < .001) and time on therapy (P < .001) were more important compared with those who had received only 1 line of therapy. Positively phrased parameters were associated with increased perceived importance. CONCLUSIONS: Even among educated, heavily pretreated patients, many commonly used clinical research terms are poorly understood. Comprehension and the perceived importance of trial endpoints vary over the course of disease. These observations may inform the design, discussion, and reporting of clinical trials.

Home visits for uncontrolled asthma among low-income adults with patient portal access.

BACKGROUND: Asthma disproportionately affects low-income and minority adults. In an era of electronic records and Internet-based digital devices, it is unknown whether portals for patient-provider communication can improve asthma outcomes. OBJECTIVE: We sought to estimate the effect on asthma outcomes of an intervention using home visits (HVs) by community health workers (CHWs) plus training in patient portals compared with usual care and portal training only. METHODS: Three hundred one predominantly African American and Hispanic/Latino adults with uncontrolled asthma were recruited from primary care and asthma specialty practices serving low-income urban neighborhoods, directed to Internet access, and given portal training. Half were randomized to HVs over 6 months by CHWs to facilitate competency in portal use and promote care coordination. RESULTS: One hundred seventy (56%) patients used the portal independently. Rates of portal activity did not differ between randomized groups. Asthma control and asthma-related quality of life improved in both groups over 1 year. Differences in improvements over time were greater for the HV group for all outcomes but reached conventional levels of statistical significance only for the yearly hospitalization rate (-0.53; 95% CI, -1.08 to -0.024). Poor neighborhoods and living conditions plus limited Internet access were barriers for patients to complete the protocol and for CHWs to make HVs. CONCLUSION: For low-income adults with uncontrolled asthma, portal access and CHWs produced small incremental benefits. HVs with emphasis on self-management education might be necessary to facilitate patient-clinician communication and to improve asthma outcomes.

Comparison of the effects of standard vs low-dose prolonged-release tacrolimus with or without ACEi/ARB on the histology and function of renal allografts.

Targeting the renin-angiotensin system and optimizing tacrolimus exposure are both postulated to improve outcomes in renal transplant recipients (RTRs) by preventing interstitial fibrosis/tubular atrophy (IF/TA). In this multicenter, prospective, open-label controlled trial, adult de novo RTRs were randomized in a 2 × 2 design to low- vs standard-dose (LOW vs STD) prolonged-release tacrolimus and to angiotensin-converting enzyme inhibitors/angiotensin II receptor 1 blockers (ACEi/ARBs) vs other antihypertensive therapy (OAHT). There were 2 coprimary endpoints: the prevalence of IF/TA at month 6 and at month 24. IF/TA prevalence was similar for LOW vs STD tacrolimus at month 6 (36.8% vs 39.5%; P = .80) and ACEi/ARBs vs OAHT at month 24 (54.8% vs 58.2%; P = .33). IF/TA progression decreased significantly with LOW vs STD tacrolimus at month 24 (mean [SD] change, +0.42 [1.477] vs +1.10 [1.577]; P = .0039). Across the 4 treatment groups, LOW + ACEi/ARB patients exhibited the lowest mean IF/TA change and, compared with LOW + OAHT patients, experienced significantly delayed time to first T cell-mediated rejection. Renal function was stable from month 1 to month 24 in all treatment groups. No unexpected safety findings were detected. Coupled with LOW tacrolimus dosing, ACEi/ARBs appear to reduce IF/TA progression and delay rejection relative to reduced tacrolimus exposure without renin-angiotensin system blockade. ClinicalTrials.gov identifier: NCT00933231.

Femtometer displacement resolution with phase-insensitive Doppler sensing.

The measurement of extremely small displacements is of utmost importance for fundamental studies and practical applications. One way to estimate a small displacement is to measure the Doppler shift generated in light reflected off a moving object, converting a displacement measurement into a frequency measurement. Here we show a sensitive device capable of measuring µHz/Hz Doppler frequency shifts corresponding to tens of femtometer displacements for a mirror oscillating at 2 Hz. While the Doppler shift measured is comparable to other techniques, the position sensitivity is orders of magnitude better, and operates over several orders of magnitude of Doppler frequency range. In addition, unlike other interferometric techniques, our device is phase insensitive, making it unusually robust to noise.

Frequency-modulated continuous-wave LiDAR compressive depth-mapping.

We present an inexpensive architecture for converting a frequency-modulated continuous-wave LiDAR system into a compressive-sensing based depth-mapping camera. Instead of raster scanning to obtain depth-maps, compressive sensing is used to significantly reduce the number of measurements. Ideally, our approach requires two difference detectors. Due to the large flux entering the detectors, the signal amplification from heterodyne detection, and the effects of background subtraction from compressive sensing, the system can obtain higher signal-to-noise ratios over detector-array based schemes while scanning a scene faster than is possible through raster-scanning. Moreover, by efficiently storing only 2m data points from m < n measurements of an n pixel scene, we can easily extract depths by solving only two linear equations with efficient convex-optimization methods.

Short-wave infrared compressive imaging of single photons.

We present a short-wave infrared (SWIR) single photon camera based on a single superconducting nanowire single photon detector (SNSPD) and compressive imaging. We show SWIR single photon imaging at a megapixel resolution with a low signal-to-background ratio around 0.6, show SWIR video acquisition at 20 frames per second and 64x64 pixel video resolution, and demonstrate sub-nanosecond resolution time-of-flight imaging. All scenes were sampled by detecting only a small number of photons for each compressive sampling matrix. In principle, our technique can be used for imaging faint objects in the mid-IR regime.

Polarization-independent atomic prism filter for removing amplified spontaneous emission.

We create an optical frequency, polarization-independent, narrow bandpass filter of 1.3 GHz (3 dB bandwidth), using the steep dispersion near the rubidium D1 atomic transitions within a prism-shaped vapor cell. This enables us to clean the amplified spontaneous emission from a laser by more than 3 orders of magnitude. Such a filter could find uses in fields such as quantum information processing and Raman spectroscopy.

Discerning the clinical relevance of biomarkers in early stage breast cancer.

PURPOSE: Prior data suggest that breast cancer patients accept significant toxicity for small benefit. It is unclear whether personalized estimations of risk or benefit likelihood that could be provided by biomarkers alter treatment decisions in the curative setting. METHODS: A choice-based conjoint (CBC) survey was conducted in 417 HER2-negative breast cancer patients who received chemotherapy in the curative setting. The survey presented pairs of treatment choices derived from common taxane- and anthracycline-based regimens, varying in degree of benefit by risk of recurrence and in toxicity profile, including peripheral neuropathy (PN) and congestive heart failure (CHF). Hypothetical biomarkers shifting benefit and toxicity risk were modeled to determine whether this knowledge alters choice. Previously identified biomarkers were evaluated using this model. RESULTS: Based on CBC analysis, a non-anthracycline regimen was the most preferred. Patients with prior PN had a similar preference for a taxane regimen as those who were PN naïve, but more dramatically shifted preference away from taxanes when PN was described as severe/irreversible. When modeled after hypothetical biomarkers, as the likelihood of PN increased, the preference for taxane-containing regimens decreased; similarly, as the likelihood of CHF increased, the preference for anthracycline regimens decreased. When evaluating validated biomarkers for PN and CHF, this knowledge did alter regimen preference. CONCLUSIONS: Patients faced with multi-faceted decisions consider personal experience and perceived risk of recurrent disease. Biomarkers providing information on likelihood of toxicity risk do influence treatment choices, and patients may accept reduced benefit when faced with higher risk of toxicity in the curative setting.

Anomalous amplification of a homodyne signal via almost-balanced weak values.

We propose precision measurements of ultra-small angular velocities of a mirror within a modified Sagnac interferometer, where the counter-propagating beams are spatially separated, using the recently proposed technique of almost-balanced weak values amplification (ABWV) [Phys. Rev. Lett.116, 100803 (2016)PRLTAO0031-900710.1103/PhysRevLett.116.100803]. The separation between the two beams provides additional amplification with respect to using collinear beams in a Sagnac interferometer. Within the same setup, the weak-value amplification technique is also performed for comparison. Much higher amplification factors can be obtained using the almost-balanced weak values technique, with the best one achieved in our experiments being as high as 1.2×107. In addition, the amplification factor monotonically increases with decreasing of the post-selection phase for the ABWV case in our experiments, which is not the case for weak-value amplification (WVA) at small post-selection phases. Both techniques consist of measuring the angular velocity. The sensitivity of the ABWV technique is ∼38 nrad/s per averaged pulse for a repetition rate of 1 Hz and ∼33 nrad/s per averaged pulse for the WVA technique.

Ultrasensitive inverse weak-value tilt meter.

We present an interferometric technique for measuring ultrasmall tilts. The information of a tilt in one of the mirrors of a modified Sagnac interferometer is carried by the phase difference between the counter-propagating laser beams. Using a small misalignment of the interferometer, orthogonal to the plane of the tilt, a bimodal (or two-fringe) pattern is induced in the beam's transverse power distribution. By tracking the mean of such a distribution, using a split detector, a sensitive measurement of the phase is performed. With 1.2 mW of continuous-wave laser power, the technique has a shot noise limited sensitivity of 56 frad/Hz and a measured noise floor of 200 frad/Hz for tilt frequencies above 2 Hz. A tilt of 200 frad corresponds to a differential displacement of 4.0 fm in our setup. The novelty of the protocol relies on signal amplification due to the misalignment and on good performance at low frequencies. A noise floor of about 70 prad/Hz is observed between 2 and 100 mHz.

Reliability of the Faces, Legs, Activity, Cry, and Consolability Scale in Assessing Acute Pain in the Pediatric Emergency Department.

OBJECTIVES: The Faces, Legs, Activity, Cry, and Consolability (FLACC) scale is one of the most widely utilized observational pain assessment scales in clinical practice. Although designed and validated to assess postoperative pain, the tool is currently applied to assess acute pain in multiple settings, including the emergency department. Scarce literature exists evaluating the reliability of the FLACC scale in the nonsurgical population and none in the emergency department. We sought to investigate the reliability of the FLACC scale in assessing acute pain in the pediatric emergency department and to examine the sensitivity of FLACC scores after the administration of analgesia. METHODS: In phase 1 of this prospective study, a series of 2 independent evaluators, blinded to each other's evaluations, scored 66 patients using the FLACC tool. Degree of concordance among the 6 dyads was used to measure interrater reliability. In phase 2, FLACC scores were obtained just before the administration of analgesia in 35 patients and measured at 30 and at 60 minutes after administration. RESULTS: Among the 6 dyads of evaluators, Kendall W demonstrated a strong concordance (27 of 30 measures; range, 0.63-1.00) for individual components of the scale and for the composite scores (range, 0.85-0.96). Significant mean reductions from preanalgesia FLACC scores [5.54; 95% confidence interval (CI), 4.79-6.30] were seen at 30 minutes (2.00; 95% CI, 1.61-2.39) and 60 minutes (1.14; 95% CI, 0.79-1.50) postanalgesia (P < 0.0001 for all comparisons). CONCLUSIONS: The FLACC scale demonstrated high interrater reliability for both individual FLACC items and total scores in a convenience sample of patients aged 6 months to 5 years in a pediatric emergency department. It seems to be an appropriate observational tool to assess acute pain in this population.

Can Anomalous Amplification be Attained without Postselection?

We present a parameter estimation technique based on performing joint measurements of a weak interaction away from the weak-value-amplification approximation. Two detectors are used to collect full statistics of the correlations between two weakly entangled degrees of freedom. Without discarding of data, the protocol resembles the anomalous amplification of an imaginary-weak-value-like response. The amplification is induced in the difference signal of both detectors allowing robustness to different sources of technical noise, and offering in addition the advantages of balanced signals for precision metrology. All of the Fisher information about the parameter of interest is collected. A tunable phase controls the strength of the amplification response. We experimentally demonstrate the proposed technique by measuring polarization rotations in a linearly polarized laser pulse. We show that in the presence of technical noise the effective sensitivity and precision of a split detector is increased when compared to a conventional continuous-wave balanced detection technique.

Mechanical Modeling of the Human Cricoid Cartilage Using Computer-Aided Design: Applications in Airway Balloon Dilation Research.

OBJECTIVES: Balloon dilation is generally considered first-line treatment for airway stenosis. Some dilation systems utilize a compliant balloon that can conform around rigid structures. Others use a noncompliant balloon that does not conform, allowing for dilation of more rigid stenoses. We hypothesized that subglottic dilation with a noncompliant balloon increases the likelihood of fracture of the cricoid when compared to a compliant balloon. METHODS: Three fresh human cricoid cartilages were placed in a universal testing system to determine the expansile force necessary for cricoid fracture. Using these data, a 3D printer was used to construct a synthetic cricoid model possessing near identical physical characteristics to the human cricoid. Simulated dilation was then performed on the model using a compliant and a noncompliant balloon. RESULTS: Human cricoid fracture occurred at 97.25 N (SD = 8.34), and the synthetic cricoid model fractured at 100.10 N (SD = 7.32). Both balloons fractured the model in every replicate experiment. Mean balloon internal pressure at fracture was 7.67 ATM (SD = 1.21) for the compliant balloon and 11.34 ATM (SD = 1.29) for the noncompliant balloon. CONCLUSIONS: These data show that fracture of the cricoid is a valid concern in balloon dilation procedures where the balloon spans the subglottis. Furthermore, the hypothesis was rejected in that the compliant balloon system was at least as likely to fracture the cricoid model as the noncompliant.

Paraxial full-field cloaking.

We complete the 'paraxial' (small-angle) ray optics cloaking formalism presented previously [Opt. Express 22, 29465 (2014)], by extending it to the full-field of light. Omnidirectionality is then the only relaxed parameter of what may be considered an ideal, broadband, field cloak. We show that an isotropic plate of uniform thickness, with appropriately designed refractive index and dispersion, can match the phase over the whole visible spectrum. Our results support the fundamental limits on cloaking for broadband vs. omnidirectionality, and provide insights into when anisotropy may be required.

Fast Hadamard transforms for compressive sensing of joint systems: measurement of a 3.2 million-dimensional bi-photon probability distribution.

We demonstrate how to efficiently implement extremely high-dimensional compressive imaging of a bi-photon probability distribution. Our method uses fast-Hadamard-transform Kronecker-based compressive sensing to acquire the joint space distribution. We list, in detail, the operations necessary to enable fast-transform-based matrix-vector operations in the joint space to reconstruct a 16.8 million-dimensional image in less than 10 minutes. Within a subspace of that image exists a 3.2 million-dimensional bi-photon probability distribution. In addition, we demonstrate how the marginal distributions can aid in the accuracy of joint space distribution reconstructions.