Recovery Metrics Research Articles

Relationships between injury kinematics, neurological recovery, and pathology following concussion.

Mild traumatic brain injury affects millions of individuals annually primarily through falls, traffic collisions, or blunt trauma and can generate symptoms that persist for years. Closed-head rotational loading is the most common cause of mild traumatic brain injury and is defined by a rapid rotational acceleration of brain tissue within an intact skull. Injury kinematics-the mechanical descriptors of injury-inducing motion-explain movement of the head, which govern energy transfer, and, therefore, determine injury severity. However, the relationship between closed-head rotational injury kinematics-such as angular velocity, angular acceleration, and injury duration-and outcome after mild traumatic brain injury is not completely understood. To address this gap in knowledge, we analysed archived surgical records of 24 swine experiencing a diffuse closed-head rotational acceleration mild traumatic brain injury against 12 sham animals. Kinematics were contrasted against acute recovery outcomes, specifically apnea time, extubation time, standing time, and recovery duration. Compared to controls, animals experiencing a mild traumatic brain injury were far more likely to have apnea (P < 0.001), shorter time to extubation (P = 0.023), and longer time from extubation to standing (P = 0.006). Using least absolute shrinkage and selection operator-based regressions, kinematic parameters, including maximum negative angular velocity and time from peak angular velocity to maximum angular deceleration, were selected to explain variation in apnea time, standing time, and recovery duration. Simplified linear models employing the least absolute shrinkage and selection operator-selected variables explained a modest degree of variation in apnea time (adjusted R 2 = 0.18), standing time (adjusted R 2 = 0.19), and recovery duration (adjusted R 2 = 0.27). Neuropathology was correlated with multiple injury kinematics, with maximum angular acceleration exhibiting the strongest correlation (R 2 = 0.66). Together, these data suggest the interplay between multiple injury kinematics, including maximum negative angular velocity (immediately preceding cessation of head motion) and time from peak angular velocity to maximum angular deceleration, best explain acute recovery metrics and neuropathology after mild traumatic brain injury in swine. Future experiments that independently manipulate individual kinematic parameters could be instrumental in developing translational diagnostics for clinical mild traumatic brain injury.

Developing a national trauma research action plan: Results from the Burn Research Gap Delphi Survey.

The 2016 National Academies of Science, Engineering and Medicine call for a national integrated, military-civilian trauma action plan to achieve zero preventable deaths and disability after injury included a proposal to establish a National Trauma Research Action Plan to "strengthen trauma research and ensure that the resources available for this research are commensurate with the importance of injury and the potential for improvement in patient outcomes." The Department of Defense funded the Coalition for National Trauma Research to generate a comprehensive research agenda spanning the continuum of trauma/burn care from prehospital to rehabilitation. The Burn/Reconstructive Surgery group represents one focus area for this research agenda development. Experts in burn and reconstructive surgery research identified gaps in knowledge, generated research questions and prioritized questions using a consensus driven Delphi survey approach. Participants were identified using established Delphi recruitment guidelines to ensure heterogeneity and generalizability with military and civilian representatives. Literature reviews informed the panel. Panelists were encouraged to use a PICO format to generate research questions: Patient/Population; Intervention; Compare/Control; Outcome. Participants ranked the priority of each question on a nine-point Likert scale, which was categorized to represent low, medium, and high priority items. Consensus was defined based on ≥60% panelist agreement. Subject matter experts generated 949 research questions in 29 Burn & 26 Reconstruction topics. Five hundred ninety-seven questions reached consensus. Of these, 338 (57%) were high-priority, 180 (30%), medium-priority, and 78 (13%) low-priority questions. Many high-priority questions translate to complex wound management and outcomes. Panel recognition that significant gaps in knowledge exist in understanding functional outcomes after injury underscores the importance of long-term recovery metrics even when studying acute injury or interventions such as resuscitation or inhalation injury. Funding agencies and burn/reconstructive surgery researchers should consider these gaps when they prioritize future research. Expert consensus, Level IV.

Refractory and Super-Refractory Status Epilepticus in Nerve Agent-Poisoned Rats Following Application of Standard Clinical Treatment Guidelines.

Nerve agents (NAs) induce a severe cholinergic crisis that can lead to status epilepticus (SE). Current guidelines for treatment of NA-induced SE only include prehospital benzodiazepines, which may not fully resolve this life-threatening condition. This study examined the efficacy of general clinical protocols for treatment of SE in the specific context of NA poisoning in adult male rats. Treatment with both intramuscular and intravenous benzodiazepines was entirely insufficient to control SE. Second line intervention with valproate (VPA) initially terminated SE in 35% of rats, but seizures always returned. Phenobarbital (PHB) was more effective, with SE terminating in 56% of rats and 19% of rats remaining seizure-free for at least 24 h. The majority of rats demonstrated refractory SE (RSE) and required treatment with a continuous third-line anesthetic. Both ketamine (KET) and propofol (PRO) led to high levels of mortality, and nearly all rats on these therapies had breakthrough seizure activity, demonstrating super-refractory SE (SRSE). For the small subset of rats in which SE was fully resolved, significant improvements over controls were observed in recovery metrics, behavioral assays, and brain pathology. Together these data suggest that NA-induced SE is particularly severe, but aggressive treatment in the intensive care setting can lead to positive functional outcomes for casualties.

Inertial Measurement Unit-Derived Ergonomic Metrics for Assessing Arm Use in Manual Wheelchair Users With Spinal Cord Injury: A Preliminary Report.

Background:Individuals with spinal cord injury (SCI) who use manual wheelchairs (MWCs) have a higher rate of rotator cuff pathology progression than able-bodied individuals.Objectives:This study aimed to test the ability of risk and recovery metrics of arm use to differentiate between (1) MWC users with SCI and matched able-bodied participants (cross-sectional matched-sample study) and (2) MWC users with rotator cuff pathology progression over 1 year from those without pathology progression (longitudinal study).Methods:Thirty-four MWC users and 34 age- and sex-matched able-bodied individuals were recruited. Upper arm risk (humeral elevation >60°) and recovery (static ≥5 seconds and humeral elevation <40°) metrics were calculated from wireless inertial measurement units (IMUs) worn on the upper arms and torso in the free-living environment. Two separate magnetic resonance imaging studies were completed and assessed for a subset of 16 MWC users approximately 1 year apart.Results:The frequency of risk events (p = .019), summated duration of recovery events (p = .025), and duration of each recovery event (p = .003) were higher for MWC users than able-bodied participants. The summated duration of risk events (p = .047), frequency of risk events (p = .027), and risk to recovery ratio (p = .02) were higher and the summated duration of recovery events (p = .036) and frequency of recovery events (p = .047) were lower for MWC users with rotator cuff pathology progression (n = 5) compared to those without progression (n = 11).Conclusion:IMU-derived metrics quantifying arm use at postures >60° and risk to recovery ratios may provide insights of potential risk factors for rotator cuff pathology progression.

Assembling Adjustment: Parergasia, Paper Technologies, and the Revision of Recovery

Drawing from research on 'paper technologies' conducted by medical historians Volker Hess and Andrew Mendelsohn, among others, this article explores how Adolf Meyer (1866-1950) and his staff at the Phipps Psychiatric Clinic used customized punch cards to develop an alternative conceptualization of schizophrenia: 'parergasia.' It begins by examining 'dementia praecox,' the conceptual precursor to both schizophrenia and parergasia, to explain how earlier paper technologies used to track patients transferred to asylums generated prognostic assumptions that precluded deinstitutionalization and community-based care. It then describes how Meyer's staff modified these technologies to define parergasia in opposition to dementia praecox and other diagnoses that resulted in prolonged hospitalization, primarily by conducting follow-up studies on discharged patients that correlated outcomes with various social factors. After demonstrating how the standardized forms used in these studies limited the possible metrics of recovery, it concludes by suggesting how Meyer'sresearch influenced leaders of the community mental health movement, and prefigured later trends in psychiatric services.

Patterns of endogenous and exogenous ovarian hormone modulation on recovery metrics across the menstrual cycle

IntroductionAs the number of female athletes competing rises globally, training methodologies should reflect sex differences across critical metrics of adaptation to training. Surrogate markers of the autonomic nervous system (ANS)...

Recovery of riverine fish assemblages after anthropogenic disturbances

AbstractDisturbances within many communities are common, but the recovery of riverine fish assemblages from anthropogenic fish kills is often not well documented. Quantification of fish community recovery is needed to assess how rapidly or whether recovery occurs without mitigation. To address this need, we evaluated the temporal dynamics of six streams located in central Illinois, including systems impacted by fish kills and an undisturbed reference system. We found species richness and the index of biotic integrity experienced dramatic shifts within the first year after the disturbance event, while fish density varied less within most streams. Interestingly, local extinctions following a kill event were not limited to only rare species, with some dominant components of the local community also lost. Some impacted streams experienced small compositional changes, similar to those within the reference system, while other streams experienced large and continued compositional shifts following disturbance. The rate of compositional change decreased significantly with time since disturbance in all locations, especially within the first year. Most metrics of recovery reached a level of relative stasis three years after the disturbance event. Based on this, we recommend disturbed streams should be monitored for at least three years to fully document recovery dynamics and to determine whether active restoration efforts are warranted. Streams which do not recover during this time frame will likely require direct intervention to achieve recovery. Our results also highlight the importance of regular stream monitoring to document a stream's baseline composition and dynamics if a disturbance were to occur.

Voluntary fishing restrictions alone do not promote growth of bryozoan-dominated biogenic habitat on the Otago shelf, southeastern New Zealand

AbstractOn the continental shelf, New Zealand bryozoans dominate ecologically-important three-dimensional benthic habitat providing structural complexity which hosts a wide variety of fauna, including economically valuable species (e.g. oysters and blue cod). The association between these species and bryozoan-dominated biogenic habitat commonly results in trawling damage to the benthos; eliminating pressure from destructive fishing practices could support bryozoan regrowth. In 2002, a voluntary fishing restriction was designated over part of one such bryozoan-dominated biogenic habitat, but the efficacy of this ban has not been assessed. Statutory marine protected areas have been proposed in the same area; they aim to achieve bryozoan protection and recovery. A comparison of the bryozoan fauna using benthic images from 2003 and 2019 from the Otago shelf, South Island, New Zealand/Te Waipounamu, Aotearoa shows that a 17-year voluntary fishing ban has been ineffective at increasing the cover and richness of bryozoan-dominated biogenic habitat on the Otago shelf. This study provides a baseline for future monitoring and develops useful metrics for recovery, while calling for further research on the biology and ecology of habitat-forming bryozoans.

Three decades of post-logging tree community recovery in naturally regenerating and actively restored dipterocarp forest in Borneo

Selective logging has affected large areas of tropical forests and there is increasing interest in how to manage selectively logged forests to enhance recovery. However, the impacts of logging and active restoration, by liberation cutting and enrichment planting, on tree community composition are poorly understood compared to trajectories of biomass recovery. Here, we assess the long-term impacts of selective logging and active restoration for biomass recovery on tree species diversity, community composition, and forest structure. We censused all stems ≥2 cm diameter at breast height (DBH) on 46 permanent plots in unlogged, primary forest in the Danum Valley Conservation Area (DVCA; 12 plots, totalling 0.6 ha) and in sites logged 23–35 years prior to the census in the Ulu Segama Forest Reserve adjacent to DVCA (34 plots, totalling 1.7 ha) in Sabah, Malaysian Borneo. Active restoration treatments, including enrichment planting and climber cutting, were implemented on 17 of the logged forest plots 12–24 years prior to the census. Total plot-level basal area and pole (5–10 cm DBH) stem density were lower in logged than unlogged forests, however no difference was found in stem density amongst saplings (2–5 cm DBH) or established trees (≥10 cm DBH). Neither basal area, nor plot-level stem density varied with time since logging at any size class, although sapling and pole stem densities were lower in actively restored than naturally regenerating logged forest. Sapling species diversity was lower in logged than unlogged forest, however there were no other significant effects of logging on tree species richness or diversity indices. Tree species composition, however, differed between logged and unlogged forests across all stem size classes (PERMANOVA), reflected by 23 significant indicator species that were only present in unlogged forest. PERMANOVA tests revealed no evidence that overall species composition changed with time since logging or with active restoration treatments at any size class. However, when naturally regenerating and actively restored communities were compared, two indicator species were identified in naturally regenerating forest and three in actively restored forests. Together our results suggest that selective logging has a lasting effect on tree community composition regardless of active restoration treatments and, even when species richness and diversity are stable, species composition remains distinct from unlogged forest for more than two decades post-harvest. Active restoration efforts should be targeted, monitored, and refined to try to ensure positive outcomes for multiple metrics of forest recovery.

Considerations in Surgical Management of Gastrointestinal Cancer in Older Patients.

The goal of this manuscript is to present new and thought-provoking information related to the surgical care of older patients. We focused on four main areas including communication, surgical pathways, the care of emergency surgery patients, and functional recovery and quality of life. We sought to answer how these areas have evolved, affecting the care of older patients. Older patients with cancer present particular challenges in relation to communication, goals, surgical treatment, and post-surgical outcomes. Communication should be clear early and during the treatment course. A multidisciplinary, multimodality, multi-phase pathway can be utilized to improve the postoperative outcomes of older patients with cancer. Functional recovery and quality of life can and should be measured in this population. Communication is complicated in cancer patients, which is made more complex with advancing age. Communication is the cornerstone of the treatment of older patients. Future research should focus on interventions to improve communication and measure quality of life and functional recovery metrics.

Relationship between training load and recovery in collegiate American football players during pre-season training

ABSTRACT Background: The purpose of this study was to examine the relationship between training load and next-day recovery in collegiate American football (AF) players during pre-season. Methods: Seventeen athletes (Linemen, n = 6; Non-linemen, n = 11) participated in the 14-day study wearing monitoring (accelerometer + heart rate) sensors during on-field practice sessions throughout pre-season to assess the physiological (PL), mechanical load (ML) and recording of session RPE (sRPE load) immediately post-practice. Prior to practice, participants completed a drop-jump reactive strength index (RSI) test and reported perceived recovery status (PRS). Loaded counter movement vertical jump was assessed before and after pre-season. Results: For every one unit increase in sRPE load, RSI declined by 0.03. Non-linemen had a lower RSI value of 73.1 units compared to linemen. For every one unit increase in ML, the PRS decreased by 0.01. Non-linemen recorded higher average ML during week 2 (ES = 1.17) compared to linemen. Non-linemen recorded higher RSI values in weeks 1 (ES = −1.41) and 2 (ES = −1.72) compared to linemen. All training load and recovery parameters were lower week 2 compared to week 1 (p < 0.05) for all players. Conclusions: Next-day RSI values were influenced by sRPE load while next-day PRS appears to be more influenced by ML. No difference in PL or sRPE load was observed been groups despite non-linemen completing a higher ML throughout the preseason. A combination of training load and recovery metrics may be needed to monitor the fatigue and state of readiness of each player.

Has Stratospheric HCl in the Northern Hemisphere Been Increasing Since 2005?

Stratospheric hydrogen chloride (HCl) is the main stratospheric reservoir of chlorine, deriving from the decomposition of chlorine-containing source gases. Its trend has been used as a metric of ozone depletion or recovery. Using the latest satellite observations, it is found that the significant increase of Northern Hemisphere stratospheric HCl during 2010–2011 can mislead the trend of HCl in recent decades. In agreement with previous studies, HCl increased from 2005 to 2011; however, when the large increase of stratospheric HCl during 2010–2011 is removed, the increasing linear trend from 2005 to 2011 becomes weak and insignificant. In addition, the linear trend of Northern Hemisphere stratospheric HCl from 2005 to 2016 is also weak and insignificant. The significant increase of HCl during 2010–2011 is attributed to a strong northern polar vortex and a weakened residual circulation, which slowed down the transport of HCl between the low-mid latitudes and the high latitudes, leading to an accumulation of HCl in the middle latitudes of the stratosphere. In addition, a weakened residual circulation leads to enhance conversion of chlorine-containing source gases of different lifetimes to HCl, thus increasing the levels of HCl. Simulations by both chemistry transport and chemistry-climate models support the result. It is further found that the joint effect of a La Niña event, the west phase of the quasi-biennial oscillation and positive anomalies of sea surface temperature in the North Pacific is responsible for the strong northern polar vortex and a weakened residual circulation.

Stress gradients interact with disturbance to reveal alternative states in salt marsh: Multivariate resilience at the landscape scale

Abstract Stress gradients influence many ecosystem processes and properties, including ecosystem recovery from and resistance to disturbance. While recent analytical approaches have advanced multivariate metrics of ecosystem resilience that allow quantification of conceptual resilience models and identification of thresholds of state change, these approaches are not often translated to landscape scales. Using natural and restored salt marshes in Louisiana, USA, we quantified plant community recovery and resistance metrics along flooding stress gradients. n‐dimensional hypervolumes of plant community biomass and structure were simulated using field data collected from disturbance‐recovery experiments. The relationships between multivariate resilience metrics and flooding stress gradients were then mapped at community‐ and landscape‐relevant scales by scaling with airborne‐derived data across the region. Greater pre‐disturbance abiotic stress decreased live below‐ground, but not above‐ground, biomass, and ultimately led to lower post‐disturbance total recovery, recovery rates and resistance of plant communities. Vegetated plots flooded &gt;52% of the time transitioned to an alternative, unvegetated state after disturbance. Mapping revealed differences in spatial patterns of resilience—highlighting low, interior marsh edges as especially vulnerable to the combination of chronic flooding stress and acute disturbance. At the landscape scale, approximately half of the area (48%) is vulnerable to state change after pulse disturbances. Synthesis. Ultimately, we quantify the ball‐and‐cup conceptual model for a salt marsh ecosystem and its alternative state, mudflat. We find that increasing abiotic stress due to climate change diminishes ecosystem resilience, but the interaction with common episodic disturbances is necessary to reveal transitions to alternative states and quantify state change thresholds. Quantifying and mapping resilience and where alternative states may exist in this fashion improves ecologists' ability to investigate the mechanisms of stress gradient control on emergent ecosystem properties while providing spatially explicit resources for managing ecosystems according to their projected resilience.

An integrated palaeoenvironmental record of Early Modern occupancy and land use within Angkor Thom, Angkor

Exploring severe social, political, or economic change in past societies can reveal adaptive pathways and strategies that may be of value to contemporary society as we prepare to adapt to this century of disruption. Episodes of large-scale transformation in past societies are often framed as ‘collapse’ – as terminal events instigated by one or more stressors. The focus on cataclysmic episodes, often related to climatic forcing, has meant that the nuance of adaptation is not well documented in historical and archaeological records, in part due to the historical lacuna that may follow periods of social disruption. Here we present a multi-proxy record of landscape and land use change from Angkor, the administrative and ceremonial core of the Angkorian kingdom in ancient Cambodia, through a period of severe climate stress and political transition in the 14th-15th centuries to the present-day. Analysis of proxy data, including geochemistry, palynology, sedimentology, and fire history, reveal a prolonged period of land use attenuation beginning in the early to mid-14th century, interrupted by a brief increase in burning and cultivation that may represent a short period of reoccupation in the mid-16th century. Agricultural activity continued to decline, despite continuing ritual activity within the site of Angkor Thom and ongoing occupation at temple sites in the Greater Angkor region, until the 17th century when metrics for secondary forest growth and landscape recovery reached consistently high levels. These results provide further evidence exposing the varied trajectories of occupation across key Cambodian urban centres, and contribute to the developing narrative of Angkor as a city that underwent transformation, rather than collapse, between the Angkorian (c. 800- c. 1450 C.E.) and Early Modern (c. 1450 - c. 1850 C.E.) periods.

QED: Using Quality-Environment-Diversity to Evolve Resilient Robot Swarms

In quality-diversity algorithms, the behavioral diversity metric is a key design choice that determines the quality of the evolved archives. Although behavioral diversity is traditionally obtained by describing the observed resulting behavior of robot controllers evaluated in a single environment, it is often more easily induced by introducing environmental diversity, i.e., by manipulating the environments in which the controllers are evaluated. This article proposes quality-environment-diversity (QED), an algorithm that repeatedly generates a random environment according to a probability distribution over environmental features (e.g., number of obstacles, arena size and robot sensor and actuator characteristics), evaluates the controller in that environment, and then describes the controller in terms of the features of that environment, the environment descriptor. Our study compares QED to three baseline task-specific and generic behavioral descriptors, in 5 different robot swarm benchmark tasks. For each task, the quality of the evolved archives is assessed by their capability to provide high-performing compensatory behaviors following injection of 250 unique faults to the robots of the swarm. The evolved archives achieve a median 2- to 3-fold reduction in the impact of the faults on the performance of the swarm. A qualitative analysis of evolved archives is done by visualizing the relation between diversity of compensatory behaviors, here called useful behavioral diversity, and fault recovery metrics. The resulting signatures indicate that, due to the diversity of environments inducing useful behavioral diversity, archives evolved by QED provide robot swarm controllers that are capable of recovering from high-impact faults.

Quantifying Asymmetry in Gait: The Weighted Universal Symmetry Index to Evaluate 3D Ground Reaction Forces.

Though gait asymmetry is used as a metric of functional recovery in clinical rehabilitation, there is no consensus on an ideal method for its evaluation. Various methods have been proposed to analyze single bilateral signals but are limited in scope, as they can often use only positive signals or discrete values extracted from time-scale data as input. By defining five symmetry axioms, a framework for benchmarking existing methods was established and a new method was described here for the first time: the weighted universal symmetry index (wUSI), which overcomes limitations of other methods. Both existing methods and the wUSI were mathematically compared to each other and in respect to their ability to fulfill the proposed symmetry axioms. Eligible methods that fulfilled these axioms were then applied using both discrete and continuous approaches to ground reaction force (GRF) data collected from healthy gait, both with and without artificially induced asymmetry using a single instrumented elbow crutch. The wUSI with a continuous approach was the only symmetry method capable of identifying GRF asymmetry differences in different walking conditions in all three planes of motion. When used with a continuous approach, the wUSI method was able to detect asymmetries while avoiding artificial inflation, a common problem reported in other methods. In conclusion, the wUSI is proposed as a universal method to quantify three-dimensional GRF asymmetries, which may also be expanded to other biomechanical signals.

Bilateral Erector Spinae Blocks Decrease Perioperative Opioid Use After Pediatric Cardiac Surgery

The present study examined the feasibility and efficacy of continuous bilateral erector spinae blocks for post-sternotomy pain in pediatric cardiac surgery. Prospective cohort study; patients were retrospectively matched 1:2 to control patients. Conditional logistic regression was used to compare dichotomous outcomes, and generalized linear models were used for continuous measures, both accounting for clusters. Quaternary children's hospital, university setting. The study comprised 10 children ages five-to-17 years undergoing elective cardiac surgery requiring cardiopulmonary bypass. Ultrasound-guided bilateral erector spinae blocks at the conclusion of the cardiac surgical procedure, with postoperative infusion of ropivacaine until chest tube removal. Postoperative management otherwise followed standardized guidelines. Patient characteristics were similar in the two groups. The median time to completion of the bilateral blocks was 16.0 minutes (interquartile range [IQR] 14.8-19.3), and no major adverse events were identified. Pain scores were low in both groups. Postoperative opioid use at 48 hours, rendered as oral morphine equivalents, was significantly reduced in the patients receiving the blocks. Cluster-adjusted squared-root-transformed means ± standard error were 0.89 ± 0.06 mg/kg for patients receiving the blocks versus 1.05 ± 0.06 mg/kg for control patients (p = 0.04; raw medians 0.81 [IQR 0.41-1.04] v 1.10 [IQR 0.78-1.35] mg/kg, respectively). There were no differences in recovery metrics, length of stay, or complications. Bilateral erector spinae blocks were associated with a reduction in opioid use in the first 48 hours after pediatric cardiac surgery compared with a matched cohort from the enhanced recovery program. Larger studies are needed to determine whether this can result in an improvement in recovery and patient satisfaction.

Optimizing the electronic health record: An inpatient sprint addresses provider burnout and improves electronic health record satisfaction.

We sought reduce electronic health record (EHR) burden on inpatient clinicians with a 2-week EHR optimization sprint. A team led by physician informaticists worked with 19 advanced practice providers (APPs) in 1 specialty unit. Over 2 weeks, the team delivered 21 EHR changes, and provided 39 one-on-one training sessions to APPs, with an average of 2.8 hours per provider. We measured Net Promoter Score, thriving metrics, and time spent in the EHR based on user log data. Of the 19 APPs, 18 completed 2 or more sessions. The EHR Net Promoter Score increased from 6 to 60 postsprint (1.0; 95% confidence interval, 0.3-1.8; P = .01). The NPS for the Sprint itself was 93, a very high rating. The 3-axis emotional thriving, emotional recovery, and emotional exhaustion metrics did not show a significant change. By user log data, time spent in the EHR did not show a significant decrease; however, 40% of the APPs responded that they spent less time in the EHR. This inpatient sprint improved satisfaction with the EHR.

Trawl fishing impacts on the status of seabed fauna in diverse regions of the globe

AbstractBottom trawl fishing is a controversial activity. It yields about a quarter of the world's wild seafood, but also has impacts on the marine environment. Recent advances have quantified and improved understanding of large‐scale impacts of trawling on the seabed. However, such information needs to be coupled with distributions of benthic invertebrates (benthos) to assess whether these populations are being sustained under current trawling regimes. This study collated data from 13 diverse regions of the globe spanning four continents. Within each region, we combined trawl intensity distributions and predicted abundance distributions of benthos groups with impact and recovery parameters for taxonomic classes in a risk assessment model to estimate benthos status. The exposure of 220 predicted benthos‐group distributions to trawling intensity (as swept area ratio) ranged between 0% and 210% (mean = 37%) of abundance. However, benthos status, an indicator of the depleted abundance under chronic trawling pressure as a proportion of untrawled state, ranged between 0.86 and 1 (mean = 0.99), with 78% of benthos groups &gt; 0.95. Mean benthos status was lowest in regions of Europe and Africa, and for taxonomic classes Bivalvia and Gastropoda. Our results demonstrate that while spatial overlap studies can help infer general patterns of potential risk, actual risks cannot be evaluated without using an assessment model that incorporates trawl impact and recovery metrics. These quantitative outputs are essential for sustainability assessments, and together with reference points and thresholds, can help managers ensure use of the marine environment is sustainable under the ecosystem approach to management.

Abstract 5384: Analytic validation of an assay to detect androgen receptor splice variant ARv7 protein expression on circulating tumor cells from prostate cancer patients

Abstract Circulating tumor cells (CTCs) can provide information on drug target expression, response to therapy, and disease prognosis from a non-invasive blood draw. Currently, investigating biomarkers on CTCs is difficult due to challenges of developing multiplexed assays that also identify rare cells. Presence of the androgen receptor splice variant ARv7 in prostate cancer cells is associated with resistance to second generation anti-androgen therapies. We report here the analytical validation of an immunofluorescence assay for characterization of ARv7 protein expression on CTCs using the RareCyte platform - an end-to-end platform that combines CTC sample preparation, multiparameter fluorescence staining, digital imaging, and single cell retrieval. Blood samples spiked with positive and negative cell lines for ARv7 expression were processed using the AccuCyte Sample Preparation System. Slides were auto-stained by immunofluorescence with the RarePlex ARv7 CTC Panel Kit comprised of a three-channel CTC detection base plus an ARv7 biomarker channel. The detection base consists of a nuclear dye, anti-CD45 antibody to exclude white blood cells, and cocktailed antibodies to cytokeratin (CK) and epithelial cell adhesion molecule (EpCAM). Stained slides were imaged with the CyteFinder Instrument. CTCs were identified using machine learning-based algorithms and confirmed by user review. Mean fluorescence intensity (MFI) measurements were used as a metric for ARv7 expression on confirmed CTCs. Analytic validation studies of the AR-V7 CTC assay were performed using 22RV1 (high), LNCaP (low), and BT-474 (negative) cell lines. Performance characteristics tested for ARv7 included accuracy, sensitivity, specificity, repeatability, and inter-stainer run coefficient of variation. Performance metrics for CTC recovery were calculated on spike-in and clinical samples. For recovery calculations, the number of CTCs found with the ARv7 assay was compared to the number of CTCs found with the CTC detection base assay. An ARv7 MFI threshold that segregated negative and positive cell lines was statistically defined. This threshold identified 80% of 22RV1 cells as positive for ARv7, 97% of BT-474 cells as negative, with an overall accuracy of 90%. When the assay was applied to clinical prostate cancer samples, staining with proper nuclear localization was observed. CTC recovery was at least as high with the ARv7 assay as with the base CTC detection assay. Citation Format: Daniel Campton, Edward Lo, Lillian Costandy, Brady Gardner, Ryan Houston, Jeffery L. Werbin, Kyla Teplitz, Daniel E. Sabath, Alisa C. Clein, Celestia S. Higano, Tanisha M. Mojica, Kristin Province, Eric P. Kaldjian, Arturo B. Ramirez, Tad George. Analytic validation of an assay to detect androgen receptor splice variant ARv7 protein expression on circulating tumor cells from prostate cancer patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5384.