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At least 145 records · Page 8

T wave alternans during exercise and atrial pacing in humans

INTRODUCTION: Evidence is accumulating that microvolt T wave alternans (TWA) is a marker of increased risk for ventricular tachyarrhythmias. Initially, atrial pacing was used to elevate heart rate and elicit TWA. More recently, a noninvasive approach has been developed that elevates heart rate using exercise. METHODS AND RESULTS: In 30 consecutive patients with a history of ventricular tachyarrhythmias, the spectral method was used to detect TWA during both atrial pacing and submaximal exercise testing. The concordance rate for the presence or absence of TWA using the two measurement methods was 84%. There was a patient-specific heart rate threshold for the detection of TWA that averaged 100 +/- 14 beats/min during exercise compared with 97 +/- 9 beats/min during right atrial pacing (P = NS). Beyond this threshold, there was a significant and comparable increase in level of TWA with decreasing pacing cycle length and increasing exercise heart rates. CONCLUSIONS: The present study is the first to demonstrate that microvolt TWA can be assessed reliably and noninvasively during exercise stress. There is a patient-specific heart rate threshold beyond which TWA continues to increase with increasing heart rates. Heart rate thresholds for the onset of TWA measured during atrial pacing and exercise stress were comparable, indicating that heart rate alone appears to be the main factor of determining the onset of TWA during submaximal exercise stress.

NASA Discipline Regulatory Physiology↗

Predicting sudden cardiac death from T wave alternans of the surface electrocardiogram: promise and pitfalls

Sudden cardiac death remains a preeminent public health problem. Despite advances in preventative treatment for patients known to be at risk, to date we have been able to identify, and thus treat, only a small minority of these patients. Therefore, there is a major need to develop noninvasive diagnostic technologies to identify patients at risk. Recent studies have demonstrated that measurement of microvolt-level T wave alternans is a promising technique for the accurate identification of patients at risk for ventricular arrhythmias and sudden cardiac death. In this article, we review the clinical data establishing the relationship between microvolt T wave alternans and susceptibility to ventricular arrhythmias. We also review the methods and technology that have been developed to measure microvolt levels of T wave alternans noninvasively in broad populations of ambulatory patients. In particular, we examine techniques that permit the accurate measurement of T wave alternans during exercise stress testing.

Review, Tutorial↗

Smart Medical Systems with Application to Nutrition and Fitness in Space

Smart medical systems are being developed to allow medical treatments to address alterations in chemical and physiological status in real time. In a smart medical system sensor arrays assess subject status, which are interpreted by computer processors which analyze multiple inputs and recommend treatment interventions. The response of the subject to the treatment is again assessed by the sensor arrays, closing the loop. An early form of "smart medicine" has been practiced in space to assess nutrition. Nutrient levels are assessed with food frequency questionnaires, which are interpreted by flight surgeons to recommend in-flight alterations in diet. In the future, sensor arrays will directly probe body chemistry. Near infrared spectroscopy can be used to noninvasively measure several blood and tissue parameters which are important in the assessment of nutrition and fitness. In particular, this technology can be used to measure blood hematocrit and interstitial fluid pH. The noninvasive measurement of interstitial pH is discussed as a surrogate for blood lactate measurement for the development and real-time assessment of exercise protocols in space. Earth-based application of these sensors are also described.

Soller, Babs R.↗

Methods and apparatus for determining cardiac output

The present invention provides methods and apparatus for determining a dynamical property of the systemic or pulmonary arterial tree using long time scale information, i.e., information obtained from measurements over time scales greater than a single cardiac cycle. In one aspect, the invention provides a method and apparatus for monitoring cardiac output (CO) from a single blood pressure signal measurement obtained at any site in the systemic or pulmonary arterial tree or from any related measurement including, for example, fingertip photoplethysmography.According to the method the time constant of the arterial tree, defined to be the product of the total peripheral resistance (TPR) and the nearly constant arterial compliance, is determined by analyzing the long time scale variations (greater than a single cardiac cycle) in any of these blood pressure signals. Then, according to Ohm's law, a value proportional to CO may be determined from the ratio of the blood pressure signal to the estimated time constant. The proportional CO values derived from this method may be calibrated to absolute CO, if desired, with a single, absolute measure of CO (e.g., thermodilution). The present invention may be applied to invasive radial arterial blood pressure or pulmonary arterial blood pressure signals which are routinely measured in intensive care units and surgical suites or to noninvasively measured peripheral arterial blood pressure signals or related noninvasively measured signals in order to facilitate the clinical monitoring of CO as well as TPR.

Cohen, Richard J.↗

Fluid Shifts: Otoacoustical Emission Changes in Response to Posture and Lower Body Negative Pressure

INTRODUCTION: The purpose of the NASA Fluid Shifts Study is to characterize fluid distribution and compartmentalization associated with long-duration spaceflight and to correlate these findings with vision changes and other elements of the visual impairment and intracranial pressure (VIIP) syndrome. VIIP signs and symptoms, as well as postflight lumbar puncture data, suggest that elevated intracranial pressure (ICP) may be associated with spaceflight-induced cephalad fluid shifts, but this hypothesis has not been tested. Due to the invasive nature of direct measures of ICP, a noninvasive technique of monitoring ICP is desired for use during spaceflight. The phase angle and amplitude of otoacoustic emissions (OAEs) have been shown to be sensitive to posture change and ICP (1, 2), therefore use of OAEs is an attractive option. OAEs are low-level sounds produced by the sensory cells of the cochlea in response to auditory stimulation. These sounds travel peripherally from the cochlea, through the oval window, to the ear canal where they can be recorded. OAE transmission is sensitive to changes in the stiffness of the oval window, occurring as a result of changes in cochlear pressure. Increased stiffness of the oval window largely affects the transmission of sound from the cochlea at frequencies between 800 Hz and 1600 Hz. OAEs can be self-recorded in the laboratory or on the ISS using a handheld device. Our primary objectives regarding OAE measures in this experiment were to 1) validate this method during preflight testing of each crewmember (while sitting, supine and in head-down tilt position), and 2) determine if OAE measures (and presumably ICP) are responsive to lower body negative pressure and to spaceflight. METHODS: Distortion-product otoacoustic emissions (DPOAEs) and transient evoked otoacoustic emissions (TEOAEs) were recorded preflight using the Otoport Advance OAE system (Otodynamics Ltd., Hatfield, UK). Data were collected in four conditions (seated, supine, 15 degrees head down tilt (HDT), and 15 degrees HDT with lower body negative pressure (LBNP)) to produce a range of ICP in each subject and test the susceptibility of OAEs to LBNP. LBNP was induced using the Russian Chibis suit to produce the same fit and pressures that would be experienced inflight during Chibis LBNP trials. Similar trials have occurred inflight on the ISS. A comparative analysis of preflight and inflight phase measurements and magnitudes was completed in both broad and narrow band frequency ranges. RESULTS: TEOAE data demonstrated notable phase shifts from 859-1640 Hz when the seated baseline condition is compared to supine, HDT, and HDT plus Chibis conditions. Changes were particularly pronounced at low frequencies and were consistent with the expected ICP changes. Preflight DPOAE magnitude data revealed changes consistent with increased ICP in two conditions at 1414 Hz, where a magnitude change (relative to the seated condition) was seen in the HDT position and in HDT plus Chibis. DISCUSSION: OAEs revealed systematic changes in phase and magnitude throughout all test conditions (including use of Chibis LBNP) that were consistent with ICP changes. Results indicate that OAEs may provide a rapid noninvasive means of monitoring ICP changes. The first two subjects are projected to complete inflight testing on the ISS in early 2016, with the full complement of 10 subjects scheduled to be complete in 2018.

Melgoza, R.↗

Validation of a Cephalad Fluid Shift Countermeasure

INTRODUCTION: This project will provide critical data required to objectively determine how an optimized thigh cuff could be incorporated into the NASA integrated physiological countermeasure suite. This project will determine if thigh cuffs used during simulated spaceflight impact intracranial pressure (ICP), ocular structure and function, and intraocular pressure (IOP) using state of-the-art techniques. Additionally, some of the same methods, hardware, and protocols will be employed in the present investigation to enable direct comparisons to the International Space Station (ISS) "Fluid Shifts" experiment with Chibis-Lower Body Negative Pressure (LBNP). This study will determine the temporal physiological responses of thigh cuff application and removal on ocular and cerebral variables (including invasive ICP) in a microgravity analog. Furthermore, this proposed study will determine tissue pressure distribution applied by thigh cuffs in order to improve comfort, mobility, and efficacy of the countermeasure. Our specific aim is to determine the efficacy of a novel thigh cuff device to mitigate cephalad fluid shifts. We hypothesize that a thigh cuff countermeasure employed in a microgravity analog will temporarily reverse or attenuate ocular and cerebral-volume-pressure variables, approaching normal Earth-based seated posture, the most frequent posture assumed in daily life. In addition, we hypothesize that the magnitude of fluid and pressure redistribution using a thigh cuff countermeasure may require a longer exposure time than that of Chibis-LBNP (using ground-based data from our "Fluid Shifts" project). This project directly addresses Critical Path Roadmap Risks and Questions regarding "Risk of Spaceflight-Induced Intracranial Hypertension/Vision Alterations," and IRP Gap VIIP13: We need to identify preventative and treatment countermeasures to mitigate changes in ocular structure and function and intracranial pressure during spaceflight. METHODS: Noninvasive measures and tissue pressure distributions beneath thigh cuffs The objectives of this study are to: 1) determine the distribution of skin surface pressures beneath the advanced thigh cuff in ten subjects, 2) calibrate the built-in pressure measurement system of the advanced thigh cuff using an industry standard device, and 3) collect subjective feedback and data on the new cuff design to allow for further adjustments prior to invasive studies. A Tekscan Industrial Sensing (I-Scan) system will measure the pressure distribution of the advanced thigh cuff against the skin. In addition, we will measure blood pooling in the thigh and record the circumference of the thigh using Hokanson strain gauge plethysmography. The advanced thigh cuff will be adjusted to obtain a skin contact pressure of 30-50 mmHg as visualized on the Tekscan system. The built-in advanced thigh cuff pressure monitor will be recorded simultaneously to allow direct comparison to the Tekscan measurements. The volunteer will then remove the thigh cuff and remain at rest for five minutes with no legging applied. The thigh cuff will be donned again and pressure measurements will be taken in the same manner for up to 10 repetitions to show reproducibility of pressure after donning. At the conclusion of the study, subjects will be asked to flex their knee, stand, walk, and sit with the thigh cuff activated. During each of these maneuvers the subject will rate their pain/comfort using a modified Borg scale. Effect of thigh cuffs on ICP during simulated microgravity Ommaya reservoir patients will be recruited from the John Wayne Cancer Institute. Ommaya reservoirs provide safe and direct access for the measurement of ICP. Subjects will be instrumented for continuous blood pressure, ECG, and invasive ICP measures. The subjects will be positioned in the upright sitting posture for a 10-minute stabilization period. After the 10-minute stabilization period, imaging measures [ICP, Optical Coherence Tomography, IOP, ocular and vascular ultrasound] will be performed. Following baseline seated measures, the subject will be positioned randomly in the supine, 15deg head-down-tilt, and 15deg head-down-tilt with thigh cuffs and measures repeated. DISCUSSION: Tests to down-select thigh cuff designs will occur in early 2016. Invasive ICP and noninvasive eye imaging tests will begin in spring 2016. Supported by NSBRI through NCC 9-58.

Macias, B.↗

Electromagnetic Pain Relief/Blocking: Feasibility Assessment

Context/Background: Astronauts use pharmaceuticals during spaceflight to manage acute and chronic pain, but use of analgesics will have drawbacks for exploration-class missions because the shelf life of these medications is limited, resupply will be curtailed, astronauts may develop tolerance and/or addiction to these medications, and side effects can include impairment of cognitive abilities. Electromagnetic devices have been developed that treat pain terrestrially by affecting neuromodulation–dubbed “electroceuticals”, these devices have varied mechanisms of action that either stimulate or suppress neural activity in the central nervous system or peripheral nerves. Objective/Purpose: The available literature was reviewed and FDA-approved pain treatments (both pharmacological and non-pharmacological), as well as those currently under development, were assessed for their suitability for use in exploration class spaceflight missions. Data Sources: Due to the COVID-19 pandemic and the resulting closure of libraries, data sources were restricted to those available digitally. Online database searches included PubMed, U.S. Patent and Trademark Office, federal grant award databases (National Aeronautics and Space Administration (NASA), Department of Defense (DoD), National Institutes of Health (NIH)), and general internet searches. More than 1,600 records were reviewed in this effort. Study Selection/Eligibility Criteria: Targeted searches included different aspects of pain management. Priority was given to review studies, to cover as much of the available literature as possible in this limited effort. Study Appraisal and Synthesis Methods/Data Extraction and Data Synthesis: The titles of the studies and the awards that were obtained by searching online databases were reviewed and further information was sought for the relevant titles. Abstracts or award summaries were generally available online; for journal abstracts, full text articles were either available online or were requested via interlibrary loan. Results: An overwhelming majority of the literature focuses on the treatment of chronic rather than acute pain because it is assumed that acute pain only rarely fails to resolve and instead transitions into chronic pain when the central nervous system becomes hypersensitized. The available electromagnetic devices marketed for pain treatment have varying levels of invasiveness, use different mechanisms of action, and have demonstrated varying efficacy when evaluated scientifically. A truly noninvasive, highly efficient device is desired for use during spaceflight. One portable, self-contained, FDA-approved device was identified that, from preliminarily assessment, best met these criteria; the device noninvasively applies pulsed shortwave therapy (PSWT) to modify pain signals from peripheral nerves, however, the device has limited battery life and the effects are relatively non-selective in type of neural signal modified. Limitations: This current effort, although extensive, did not identify a comprehensive list of all alternatives for pain treatment. Once the pandemic limitations are lifted, a longer, more thorough effort may find additional options. Conclusions/Implications: The ideal electromagnetic pain treatment device for use on exploration-class spaceflight missions does not yet exist, but it may be available soon. It is not feasible for NASA to develop medical devices due to the schedule constraints for pending exploration-class missions, but adapting a promising device that is already FDA-approved might be an option. Monitoring research that is ongoing at other federal agencies is recommended, and further review of the candidate PSWT device identified in this current effort may be warranted.

Carol Mullenax↗

Electromagnetic Pain Relief/Blocking: Feasibility Assessment

CONTEXT/BACKGROUND Astronauts use pharmaceuticals during spaceflight to manage acute and chronic pain, but use of analgesics will have drawbacks for exploration-class missions because the shelf life of these medications is limited, resupply will be curtailed, astronauts may develop tolerance and/or addiction to these medications, and side effects can include impairment of cognitive abilities. Electromagnetic devices have been developed that treat pain terrestrially by affecting neuromodulation–dubbed “electroceuticals”, these devices have varied mechanisms of action that either stimulate or suppress neural activity in the central nervous system or peripheral nerves. OBJECTIVE/PURPOSE The available literature was reviewed and FDA-approved pain treatments (both pharmacological and non-pharmacological), as well as those currently under development, were assessed for their suitability for use in exploration class spaceflight missions. DATA SOURCES Due to the COVID-19 pandemic and the resulting closure of libraries, data sources were restricted to those available digitally. Online database searches included PubMed, U.S. Patent and Trademark Office, federal grant award databases (National Aeronautics and Space Administration (NASA), Department of Defense (DoD), National Institutes of Health (NIH)), and general internet searches. More than 1,600 records were reviewed in this effort. STUDY SELECTION/ELIGIBILITY CRITERIA Targeted searches included different aspects of pain management. Priority was given to review studies, to cover as much of the available literature as possible in this limited effort. STUDY APPRAISAL AND SYNTHESIS METHODS/DATA EXTRACTION AND DATA SYNTHESIS The titles of the studies and the awards that were obtained by searching online databases were reviewed and further information was sought for the relevant titles. Abstracts or award summaries were generally available online; for journal abstracts, full text articles were either available online or were requested via interlibrary loan. RESULTS An overwhelming majority of the literature focuses on the treatment of chronic rather than acute pain because it is assumed that acute pain only rarely fails to resolve and instead transitions into chronic pain when the central nervous system becomes hypersensitized. The available electromagnetic devices marketed for pain treatment have varying levels of invasiveness, use different mechanisms of action, and have demonstrated varying efficacy when evaluated scientifically. A truly noninvasive, highly efficient device is desired for use during spaceflight. One portable, self-contained, FDA-approved device was identified that, from preliminarily assessment, best met these criteria; the device noninvasively applies pulsed shortwave therapy (PSWT) to modify pain signals from peripheral nerves, however, the device has limited battery life and the effects are relatively non-selective in type of neural signal modified. LIMITATIONS This current effort, although extensive, did not identify a comprehensive list of all alternatives for pain treatment. Once the pandemic limitations are lifted, a longer, more thorough effort may find additional options. CONCLUSIONS/IMPLICATIONS The ideal electromagnetic pain treatment device for use on exploration-class spaceflight missions does not yet exist, but it may be available soon. It is not feasible for NASA to develop medical devices due to the schedule constraints for pending exploration-class missions, but adapting a promising device that is already FDA-approved might be an option. Monitoring research that is ongoing at other federal agencies is recommended, and further review of the candidate PSWT device identified in this current effort may be warranted.

C A Mullenax↗

The Role of Quantum Science Concepts in Enhancing Sensing and Imaging Technologies: Applications for Biology: Proceedings of a Workshop

Quantum concepts hold the potential to enable significant advances in sensing and imaging technologies that could be vital to the study of biological systems. The workshop Quantum Science Concepts in Enhancing Sensing and Imaging Technologies: Applications for Biology, held online March 8–10, 2021, was organized to examine the research and development needs to advance biological applications of quantum technology. Hosted by the National Academies of Sciences, Engineering, and Medicine, the event brought together experts working on state-of-the-art, quantum-enabled technologies and scientists who are interested in applying these technologies to biological systems. Through talks, panels, and discussions, the workshop facilitated a better understanding of the current and future biological applications of quantum-enabled technologies in fields such as microbiology, molecular biology, cell biology, plant science, mycology, and many others. The workshop was organized around three main themes. The first, quantum in biology, examined quantum concepts that are hypothesized to be important for life processes and that researchers are working to observe through biological imaging and sensing. The second, quantum for biology, addressed ways to use quantum concepts to enhance technologies for biological imaging and sensing. The third, biology for quantum, offered a wider discussion of how the frontiers of biological imaging and sensing could enable future study using quantum concepts, tools, or technologies. Throughout the workshop, participants identified a wide range of emerging approaches and opportunities at the intersection of quantum physics and biological sensing and imaging. During the workshop, there were some differences in how each speaker defined the term quantum. During one of the panels, Prem Kumar offered thoughts on what phenomena are classical versus quantum, explaining that techniques get progressively more quantum as you move from just having superposition to having superposition with measurement and entanglement. Another explanation from Clarice Aiello delineates the definition into several levels. This includes a base level of “quantum-ness,” which reflects that all matter is made of atoms, and when these particles are isolated they behave based on quantum mechanical principles. A second level is related to quantum coherence, where a single quantum object might be found in a coherent superposition state. A final level, which she described as the quantum-entangled level, involves multiple quantum systems which are entangled among themselves. Overall, the workshop touched on concepts such as superposition, entanglement, and squeezing and their potential implications for communication, computing, and simulation, in addition to the workshop’s main focal area, biological sensing and imaging. At the opening of the workshop, Thorsten Ritz of the University of California, Irvine, identified two questions at the heart of quantum biology: Is the machinery of life quantum mechanical, and can quantum mechanics be used to study the machinery of life in new ways? Participants highlighted systems in which researchers have explored these questions, from the vast array of molecular interactions involved in biological processes such as photosynthesis, to the mechanics involved in cellular functions such as differentiation and aggregation, to the role of oscillating magnetic fields in flight orientation among birds. Sensing and imaging technologies are crucial to biological research; these technologies could both enhance the study of quantum effects and be enhanced by quantum concepts. A critical challenge in biological research is to develop imaging and sensing tools that do not damage or interfere with the often fragile and fleeting systems being studied. Attendees discussed a variety of established and emerging technologies that could enhance noninvasive biological imaging, including single- and two-photon spectroscopy, single-molecule spectroscopy, quantum illumination, ghost imaging, and cryo-electron microscopy. One example came from Marlan Scully who gave a keynote address on the first day of the workshop. Scully emphasized the use of different laser technologies, which exhibit coherence and other quantum properties, in moving toward real-world biological applications, such as the detection of SARS-CoV-2. Both tools and theory will play an important role in advancing quantum biology research and applications. Several participants suggested theorists and experimentalists should work in tandem to understand and model biological processes. While physics often reduces systems to their simplest forms for fundamental insights, participants also noted the value of observing and understanding biological systems in all their “messiness,” capturing both the inner workings of biological systems and the complex interactions that occur within and between organisms. In discussions among participants, several attendees stressed the need to match emerging tools with the right scientific questions. Rather than developing quantum technologies as “a hammer looking for a nail,” participants emphasized a focus on exploring the problems these technologies are best suited to address. For example, it is important to consider the size of the phenomenon being studied, the timescales that are important in answering the scientific question, and other relevant considerations. Every tool along the spectrum from classical to quantum involves its own set of trade-offs. For example, Ted Laurence of the Lawrence Livermore National Laboratory said that quantum measurements, such as single photon counting, fluorescence transitions, and lasers, can take longer to produce the same results as classical measurements. These quantum measurements, however, do not require calibration and can enable new research questions to be answered. Prem Kumar, Northwestern University, noted that, despite their promise, quantum approaches should not be used simply for the sake of using quantum, especially in situations where classical approaches better meet the needs of the researcher. Understanding and applying quantum concepts could enable advances in a wide range of application areas including energy, synthetic biology, medicine, and sustainability. For example, Michelle O’Malley, University of California, Santa Barbara, described how improved noninvasive imaging approaches could help capture the complex interactions and functions involved in the breakdown of organic matter by microbial communities and lead to new technologies for capturing valuable products from plant waste. Several other participants discussed needs in tracking the movement of metabolites and molecules in microbial communities for insights into nutrient cycling in environments such as soil. Margaret Ahmad, Sorbonne University, discussed potential opportunities to leverage the magnetic properties of cryptochromes to advance new treatment approaches for diseases such as COVID-19 and cancer. Looking toward the future development of the field, participants discussed challenges to advancing quantum biology that arise from disciplinary disconnects between physicists and biologists. The siloing of academic research disciplines represents a significant barrier to progress. Disconnects in terminology, motivations and priorities, and structural barriers to collaborative work underscore the need for concerted efforts to bridge these divides. Attendees and speakers offered suggestions for resolving these divergences, establishing a shared language, moving the field forward, and fostering meaningful feedback between disciplines. Overall, participants stressed a need for balance, open communication, collaboration, unity, and clear dialogue on trade-offs between quantum and classical approaches. Keiko Torii, The University of Texas at Austin, said that the best collaborations happen when the project provides mutual advantages that can show off everyone’s talents, each team finds the work interesting, and partners develop a camaraderie to pursue new knowledge. To enable near- and long-term opportunities in this space, participants suggested that exploratory, high-risk funding could improve existing instrumentation to explore quantum enhancement collaboratively. They also emphasized the need for collaboration between quantum physicists and sensing/imaging scientists, which could be advanced through a dedicated quantum biology investigator program. People, even more than technology, will be crucial to the future of quantum biology. Participants explored training, education, and workforce needs to further develop this burgeoning field and cultivate the next generation of scientists. While many programs are still in their nascent stages, participants highlighted examples of approaches and programs being developed at various types of institutions to engage students and professional scientists in quantum biology research. Several participants stressed the need for an inclusive approach, spanning disciplines as well as communities to foster a diverse field fueled by the intellectual contributions of a wide range of people, including historically under-resourced schools and students. To increase awareness and excitement about quantum physics and related areas of biology, attendees suggested capitalizing on the “buzz” around quantum. Several participants emphasized the need to start early, introducing students to quantum concepts and their appealing “weirdness” in K–12 education. Engaging students early—before they become entrenched in traditional disciplinary siloes as typically happens in graduate school—could help to galvanize interest in the area and foster a generation of scientists with the interdisciplinary mindset and skills needed to advance this interdisciplinary field. While these efforts could be advanced at many levels and across multiple sectors, several participants suggested a national quantum biology center could be a valuable hub to coordinate and support quantum biology education and workforce development across academia, industry, and government.

59 BASIC BIOLOGICAL SCIENCES↗

An Automatic Processing Framework for In Situ Determination of Ecohydrological Root Water Content by Ground-Penetrating Radar

This report concerns Root water content (RWC) as a vital component in water flux in soil-plant-atmosphere continuum. Knowledge of RWC helps to better understand the root function and the soil-root interaction and improves water cycle modeling. However, due to the lack of appropriate methods, field monitoring of RWC is seriously constrained. In this study, we used ground-penetrating radar (GPR), a common geophysical technique, to characterize RWC of coarse roots noninvasively. An automatic GPR data processing framework was proposed to (1) identify hyperbolic root reflections and locate roots in GPR images and (2) extract waveform parameters from the reflected wave of identified roots. These waveform parameters were then used to establish an empirical model and a semiempirical model to determine RWC. We validated the developed models using GPR root data at three antenna center frequencies (500 MHz, 900 MHz, and 2 GHz) that were produced from simulation experiments (with RWC ranging from 70% to 150%) and field experiments in sandy soils (with RWC ranging from 66% to 144%). Our results show that both the empirical and the semiempirical models achieved a good performance in estimating RWC with similar accuracy, i.e., the prediction error [root-mean-square error (RMSE)] was less than 8% for the simulation data and 12% for the field data. For both models, the accuracy of RWC estimation was the highest when applied to 2-GHz data. This study renders a new opportunity to determine RWC under field conditions that enhances the application of GPR for root study and the understanding and modeling of ecohydrology in the rhizosphere.

54 ENVIRONMENTAL SCIENCES↗

A Pseudo‐Surfactant Chemical Permeation Enhancer to Treat Otitis Media via Sustained Transtympanic Delivery of Antibiotics

Abstract Chemical permeation enhancers (CPEs) represent a prevalent and safe strategy to enable noninvasive drug delivery across skin‐like biological barriers such as the tympanic membrane (TM). While most existing CPEs interact strongly with the lipid bilayers in the stratum corneum to create defects as diffusion paths, their interactions with the delivery system, such as polymers forming a hydrogel, can compromise gelation, formulation stability, and drug diffusion. To overcome this challenge, differing interactions between CPEs and the hydrogel system are explored, especially those with sodium dodecyl sulfate (SDS), an ionic surfactant and a common CPE, and those with methyl laurate (ML), a nonionic counterpart with a similar length alkyl chain. Notably, the use of ML effectively decouples permeation enhancement from gelation, enabling sustained delivery across TMs to treat acute otitis media (AOM), which is not possible with the use of SDS. Ciprofloxacin and ML are shown to form a pseudo‐surfactant that significantly boosts transtympanic permeation. The middle ear ciprofloxacin concentration is increased by 70‐fold in vivo in a chinchilla AOM model, yielding superior efficacy and biocompatibility than the previous highest‐performing formulation. Beyond improved efficacy and biocompatibility, this single‐CPE formulation significantly accelerates its progression toward clinical deployment.

Engineering↗

Photoinduced Melting of V 4 O 7 Correlated State

The compound V 4 O 7 is one of the Magnéli phase (V n O 2n - 1 , n = 3, 4, …, 9) correlated vanadium oxides with distinct intriguing electronic and structural properties. The possibility to manipulate the phase state of V 4 O 7 on an ultrafast time scale by light makes this material promising for potential applications in photonics, optoelectronics, quantum, and neuromorphic circuit design. In this work, the ultrafast spectroscopy of V 4 O 7 reveals the second-order nature of the photoinduced insulator-to-metal transition, emphasizing electronic and lattice contributions. The findings reveal the influence of the laser excitation level and temperature on these dynamics, providing a comprehensive understanding of V 4 O 7 structural changes and response to external stimuli. The phenomenological model based on the Landau–Ginzburg formalism provides a robust framework for explaining the photoinduced transition dynamics, showing a detailed picture of the light interaction with the electronic and lattice subsystems. This integrated approach significantly enhances the understanding of V 4 O 7 complex behavior upon photoexcitation, opening new possibilities for developing new optoelectronic devices and noninvasive optical control of the phase transition pathways in vanadates.

36 MATERIALS SCIENCE↗

Multihead Attention U‐Net for Magnetic Particle Imaging–Computed Tomography Image Segmentation

Magnetic particle imaging (MPI) is an emerging noninvasive molecular imaging modality with high sensitivity and specificity, exceptional linear quantitative ability, and potential for successful applications in clinical settings. Computed tomography (CT) is typically combined with the MPI image to obtain more anatomical information. Herein, a deep learning‐based approach for MPI‐CT image segmentation is presented. The dataset utilized in training the proposed deep learning model is obtained from a transgenic mouse model of breast cancer following administration of indocyanine green (ICG)‐conjugated superparamagnetic iron oxide nanoworms (NWs‐ICG) as the tracer. The NWs‐ICG particles progressively accumulate in tumors due to the enhanced permeability and retention (EPR) effect. The proposed deep learning model exploits the advantages of the multihead attention mechanism and the U‐Net model to perform segmentation on the MPI‐CT images, showing superb results. In addition, the model is characterized with a different number of attention heads to explore the optimal number for our custom MPI‐CT dataset.

Juhong, Aniwat↗

Shortwave‐Infrared‐Emitting Nanoprobes for CD8 Targeting and In Vivo Imaging of Cytotoxic T Cells in Breast Cancer

Checkpoint immunotherapy has made great strides in the treatment of solid tumors, but many patients do not respond to immune checkpoint inhibitors. Identification of tumor‐infiltrating cytotoxic T cells (CTLs) has the potential to stratify patients and monitor immunotherapy responses. In this study, the design of cluster of differentiation (CD8 + ) T cell‐targeted nanoprobes that emit shortwave infrared (SWIR) light in the second tissue‐transparent window for noninvasive, real‐time imaging of CTLs in murine models of breast cancer is presented. SWIR‐emitting rare‐earth nanoparticles encapsulated in human serum albumin are conjugated with anti‐CD8α to target CTLs with high specificity. CTL targeting is validated in vitro through binding of nanoprobes to primary mouse CTLs. The potential for the use of SWIR fluorescence intensity to determine CTL presence is validated in two syngeneic mammary fat pad tumor models, EMT6 and 4T1, which differ in immune infiltration. SWIR imaging using CD8‐targeted nanoprobes successfully identifies the presence of CTLs in the more immunogenic EMT6 model, while imaging confirms the lack of substantial immune infiltration in the nonimmunogenic 4T1 model. In this work, the opportunity for SWIR imaging using CD8‐targeted nanoprobes to assess CTL infiltration in tumors for the stratification and monitoring of responders to checkpoint immunotherapy is highlighted.

Shah, Jay V.↗

Microstructural and chemical characterization of a purple pigment from a Faiyum mummy portrait

Results are presented from analyses that were conducted to explain the presence of chromium, detected noninvasively using energy dispersive X-ray fluorescence (XRF), in the unusually large (2-3mm diameter) rough gem-like purple pigment particles in the paint used for a Faiyum mummy portrait. An approximately 50 µm diameter particle of the chromium-containing purple pigment was extracted from the Portrait of a Bearded Man, dated to Roman Imperial Egypt in the second century, circa 170-180 CE, accession #32.6 in the Walters Art Museum collection. The particle was characterized using energy dispersive X-ray fluorescence analysis, electron microscopy, diffraction, and atom probe tomography. It is demonstrated that the purple pigment particle is a heterogeneous organic pigment, specifically, a lake pigment likely derived from either plant or insect matter, which contains minor percentages of both transition metals and alkali / alkali earth metals, with nanometer-scale crystallites of lead carbonates and sulfates. The analyses revealed for the first time the nanoscale microstructure and stratigraphy in an ancient lake pigment. Results suggest that similarities with respect to time-period and place of production may be developed among unprovenienced Faiyum mummy portraits to help localize workshops or artists, using analyses focused on lake pigments to characterize specifically metal-based mordants.

36 MATERIALS SCIENCE↗

A NIR fluorescent smart probe for imaging tumor hypoxia

Abstract Background Tumor hypoxia is a characteristic of paramount importance due to low oxygenation levels in tissue negatively correlating with resistance to traditional therapies. The ability to noninvasively identify such could provide for personalized treatment(s) and enhance survival rates. Accordingly, we recently developed an NIR fluorescent hypoxia‐sensitive smart probe ( NO 2 ‐Rosol ) for identifying hypoxia via selectively imaging nitroreductase (NTR) activity, which could correlate to oxygen deprivation levels in cells, thereby serving as a proxy. We demonstrated proof of concept by subjecting a glioblastoma (GBM) cell line to extreme stress by evaluating such under radiobiological hypoxic ( p O 2 ≤ ~0.5%) conditions, which is a far cry from representative levels for hypoxia for brain glioma ( p O 2 = ~1.7%) which fluctuate little from physiological hypoxic ( p O 2 = 1.0‐3.0%) conditions. Aim We aimed to evaluate the robustness, suitability, and feasibility of NO 2 ‐Rosol for imaging hypoxia in vitro and in vivo via assessing NTR activity in diverse GBM models under relevant oxygenation levels ( p O 2 = 2.0%) within physiological hypoxic conditions that mimic oxygenation levels in GBM tumor tissue in the brain. Methods We evaluated multiple GBM cell lines to determine their relative sensitivity to oxygenation levels via measuring carbonic anhydrase IX (CAIX) levels, which is a surrogate marker for indirectly identifying hypoxia by reporting on oxygen deprivation levels and upregulated NTR activity. We evaluated for hypoxia via measuring NTR activity when employing NO 2 ‐Rosol in in vitro and tumor hypoxia imaging studies in vivo. Results The GBM39 cell line demonstrated the highest CAIX expression under hypoxic conditions representing that of GBM in the brain. NO 2 ‐Rosol displayed an 8‐fold fluorescence enhancement when evaluated in GBM39 cells ( p O 2 = 2.0%), thereby establishing its robustness and suitability for imaging hypoxia under relevant physiological conditions. We demonstrated the feasibility of NO 2 ‐Rosol to afford tumor hypoxia imaging in vivo via it demonstrating a tumor‐to‐background of 5 upon (i) diffusion throughout, (ii) bioreductive activation by NTR activity in, and (iii) retention within, GBM39 tumor tissue. Conclusion We established the robustness, suitability, and feasibility of NO 2 ‐Rosol for imaging hypoxia under relevant oxygenation levels in vitro and in vivo via assessing NTR activity in GBM39 models.

Hettie, Kenneth S.↗

Improving the accessibility and transferability of machine learning algorithms for identification of animals in camera trap images: MLWIC2

Motion-activated wildlife cameras (or “camera traps”) are frequently used to remotely and noninvasively observe animals. The vast number of images collected from camera trap projects has prompted some biologists to employ machine learning algorithms to automatically recognize species in these images, or at least filter-out images that do not contain animals. These approaches are often limited by model transferability, as a model trained to recognize species from one location might not work as well for the same species in different locations. Furthermore, these methods often require advanced computational skills, making them inaccessible to many biologists. We used 3 million camera trap images from 18 studies in 10 states across the United States of America to train two deep neural networks, one that recognizes 58 species, the “species model,” and one that determines if an image is empty or if it contains an animal, the “empty-animal model.” Our species model and empty-animal model had accuracies of 96.8% and 97.3%, respectively. Furthermore, the models performed well on some out-of-sample datasets, as the species model had 91% accuracy on species from Canada (accuracy range 36%–91% across all out-of-sample datasets) and the empty-animal model achieved an accuracy of 91%–94% on out-of-sample datasets from different continents. Our software addresses some of the limitations of using machine learning to classify images from camera traps. By including many species from several locations, our species model is potentially applicable to many camera trap studies in North America. We also found that our empty-animal model can facilitate removal of images without animals globally. We provide the trained models in an R package (MLWIC2: Machine Learning for Wildlife Image Classification in R), which contains Shiny Applications that allow scientists with minimal programming experience to use trained models and train new models in six neural network architectures with varying depths.

59 BASIC BIOLOGICAL SCIENCES↗

Determining the twist angle of stacked MoS 2 layers using machine learning-assisted low-frequency interlayer Raman fingerprints

The investigation of twisted stacked few-layer MoS 2 has revealed novel electronic, optical, and vibrational properties over an extended period. For the successful integration of twisted stacked few-layer MoS 2 into a wide range of applications, it is crucial to employ a noninvasive, versatile technique for characterizing the layered architecture of these complex structures. Here, in this work, we introduce a machine learning-assisted low-frequency Raman spectroscopy method to characterize the twist angle of few-layer stacked MoS 2 samples. A feedforward neural network (FNN) is utilized to analyze the low-frequency breathing mode as a function of the twist angle. Moreover, using finite difference method (FDM) and density functional theory (DFT) calculations, we show that the low-frequency Raman spectra of MoS 2 are mainly influenced by the effect of the nearest and second nearest layers. A new improved linear chain model (TA-LCM) with taking the twist angle into the consideration is developed to understand the interlayer breathing modes of stacked few-layer MoS 2 . This approach can be extended to other 2D materials systems and provides an intelligent way to investigate naturally stacked and twisted interlayer interactions.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗