Estimating the Practice-Level and National Cost Burden of Treatment-Related Prior Authorization for Academic Radiation Oncology Practices.

PURPOSE: Prior authorization (PA) imposes significant time burdens on radiation oncology practices, but its financial impact has not been characterized. We used time-driven activity-based costing (TDABC) to assess the cost burden of treatment-related PA events at an academic radiation oncology practice. We then estimated annual costs for an academic practice and academic practices nationally. METHODS AND MATERIALS: Using internal analyses, we created TDABC process maps for treatment-related PA events at an academic radiation oncology practice. Using published compensation data, internal workhour estimates, and supervisory requirements, we calculated the cost of each PA event and annual costs. Using data from the 2017 American Society for Radiation Oncology Workforce Survey and the 2018 American Society for Radiation Oncology Prior Authorization Survey, we estimated annual PA costs for academic medical centers nationally. RESULTS: We successfully created TDABC process maps for treatment-related PA events at an academic radiation oncology practice. There were significant time and cost burdens for all events (range: 51-95 minutes, $28-$101 US dollars [USD]), with significant increases when peer-to-peer discussion was required (range: 92-95 minutes, $75-$101 USD). Annual treatment-related PA departmental costs were estimated to be $491,989 USD, with approved treatments accounting for the majority (94%; $463,027 USD). Nationally, annual treatment-related PA costs were estimated to be $40,125,848 USD, with approved treatments accounting for the majority (86%; $34,632,620 USD). CONCLUSION: TDABC can be used to estimate the cost burden of PA events. These burdens are significant and translate into massive organizational costs. Our national estimates highlight the tremendous cost of PA for academic radiation oncology practices, with the majority of costs related to approved treatments.

Physics-Based Modelling and Simulation of Multibeam Echosounder Perception for Autonomous Underwater Manipulation.

One of the key distinguishing aspects of underwater manipulation tasks is the perception challenges of the ocean environment, including turbidity, backscatter, and lighting effects. Consequently, underwater perception often relies on sonar-based measurements to estimate the vehicle's state and surroundings, either standalone or in concert with other sensing modalities, to support the perception necessary to plan and control manipulation tasks. Simulation of the multibeam echosounder, while not a substitute for in-water testing, is a critical capability for developing manipulation strategies in the complex and variable ocean environment. Although several approaches exist in the literature to simulate synthetic sonar images, the methods in the robotics community typically use image processing and video rendering software to comply with real-time execution requirements. In addition to a lack of physics-based interaction model between sound and the scene of interest, several basic properties are absent in these rendered sonar images-notably the coherent imaging system and coherent speckle that cause distortion of the object geometry in the sonar image. To address this deficiency, we present a physics-based multibeam echosounder simulation method to capture these fundamental aspects of sonar perception. A point-based scattering model is implemented to calculate the acoustic interaction between the target and the environment. This is a simplified representation of target scattering but can produce realistic coherent image speckle and the correct point spread function. The results demonstrate that this multibeam echosounder simulator generates qualitatively realistic images with high efficiency to provide the sonar image and the physical time series signal data. This synthetic sonar data is a key enabler for developing, testing, and evaluating autonomous underwater manipulation strategies that use sonar as a component of perception.

Radiation Therapy Adherence Among Patients Experiencing Homelessness.

PURPOSE: Radiation therapy is a valuable, yet time- and resource-intense therapy. Patients experiencing homelessness (PEH) face many barriers related to the timely receipt of radiation therapy. Owing to a paucity of data regarding cancer treatment and homelessness, clinicians have a limited evidence base when recommending therapy to PEH. This study was performed to evaluate adherence to radiation therapy treatment regimens in PEH with cancer. METHODS AND MATERIALS: The study cohort was primarily derived from the Vanderbilt University Medical Center Homeless Health Services program. Patients in the Homeless Health Services program with radiation oncology visits were identified by query of the electronic medical record. Manual chart review was performed to gather standard treatment parameters and data describing missed appointments. A comparison group of patients not experiencing homelessness (non-PEH) was generated by aggregating appointment data for all other patients receiving similar treatments at Vanderbilt University Medical Center during multiple, consecutive years. RESULTS: In the study, 3408 PEH were identified, of whom 48 underwent radiation oncology consultation. Thirty-two were prescribed at least 1 course of radiation therapy, for a total of 54 unique courses. Out of these courses, 34 (62.9%) were completed as prescribed without delay, 12 (22.2%) were completed with delay(s), and 8 (14.8%) were not fully completed. Although the PEH cohort had significantly higher rates of delayed and undelivered fractions, the proportion of delayed or incomplete courses was not significantly different from the comparison group of non-PEH, particularly for courses with 10 or fewer fractions. Reasons for missed appointments for PEH were variable. CONCLUSIONS: This is the first publication describing adherence to radiation therapy in PEH. Our data suggest that PEH are as likely as non-PEH to complete a course of radiation therapy, albeit with more treatment interruptions. When treatment courses of >10 fractions are expected, PEH may benefit from more hypofractionated regimens, provided they have equivalent clinical efficacy to longer regimens. Documenting reasons for missed appointments will be essential to further understanding the needs of PEH. This study serves as a foundation for further analysis regarding homelessness and radiation therapy.

The "Look Ahead" Technique: A Novel Way to Engage Medical Students in the Radiology Reading Room.

RATIONALE AND OBJECTIVES: Engaging medical students during a radiology course can be challenging. We sought a way to actively engage students with live cases, allow them to interact with the picture archiving and communication system workstation, and experience what it is like to be a radiologist. MATERIALS AND METHODS: Medical students enrolled in one of three radiology courses between May 2016 and June 2017 were eligible. The "Look Ahead" technique is as follows: a preceptor identifies several nonurgent imaging studies and allows the students to view the images first and make independent observations and conclusions. When ready, the students present their findings, receive feedback, and observe the preceptor generate a final report. Students completed the postcourse survey comparing the "Look Ahead" technique with the current standard (observing a preceptor interpret imaging studies with accompanying teaching points). RESULTS: Thirty-four (56.7%) of 60 potential respondents completed the postcourse survey. Of these 34, 24 (70.6%) reported at least one reading room case (mean 4.6) in which the technique was employed, with a mean of 2.4 unique preceptors. When compared to the current standard (0 = not to 100 = very interested/engaged/valuable/memorable), the "Look Ahead" technique was associated with increased student-reported interest (92.5 vs 75.1, p < 0.01), engagement (94.0 vs 70.3, p < 0.01), educational value (92.5 vs 73.2, p < 0.01), memorability of the case (88.5 vs 73.2, p < 0.01) and of accompanying teaching points (90.1 vs 76.7, p < 0.01). CONCLUSION: The "Look Ahead" technique is a meaningful and engaging teaching method, which students find "interesting," "valuable," and "memorable."

Secondary malignancy following stereotactic radiosurgery for benign neurologic disease: A cohort study and review of the literature.

Radiation-associated malignancy and malignant transformation are risks associated with stereotactic radiosurgery (SRS); however, incidence is uncertain. The purpose of our study is to present the rate of radiation-associated malignancy and malignant transformation at our institution. After IRB approval, we undertook a retrospective cohort study evaluating patients treated with Gamma Knife® or linac-based SRS between 1990 and 2014 for benign CNS pathology with at least 5 years of clinical follow-up. Risk of transformation was calculated using the Kaplan-Meier method. A total of 273 patients met selection criteria. Median clinical follow-up after SRS was 11 years (range 5-27). Over 3,216 patient-years following SRS, we found zero cases of radiation-associated malignancy and two cases of radiation-associated malignant transformation for a crude rate of 0.73% or case rate of 0.62 per 1,000 patient-years. The Kaplan-Meier risk of malignant transformation at 5, 10, and 15 years was 0.4% (95% CI 0.05% 2.6%). These data support the continued use of SRS for benign intracranial pathology without significant concern for secondary malignancy.

Combining multiparametric MRI with receptor information to optimize prediction of pathologic response to neoadjuvant therapy in breast cancer: preliminary results.

Pathologic complete response following neoadjuvant therapy (NAT) is used as a short-term surrogate marker of eventual outcome in patients with breast cancer. Analyzing voxel-level heterogeneity in MRI-derived parametric maps, obtained before and after the first cycle of NAT ([Formula: see text]), in conjunction with receptor status, may improve the predictive accuracy of tumor response to NAT. Toward that end, we incorporated two MRI-derived parameters, the apparent diffusion coefficient and efflux rate constant, with receptor status in a logistic ridge-regression model. The area under the curve (AUC) and Brier score of the model computed via 10-fold cross validation were 0.94 (95% CI: 0.85, 0.99) and 0.11 (95% CI: 0.06, 0.16), respectively. These two statistics strongly support the hypothesis that our proposed model outperforms the other models that we investigated (namely, models without either receptor information or voxel-level information). The contribution of the receptor information was manifested by an 8% to 15% increase in AUC and a 14% to 21% decrease in Brier score. These data indicate that combining multiparametric MRI with hormone receptor status has a high likelihood of improved prediction of pathologic response to NAT in breast cancer.

Transcriptome sequencing and characterization of Symbiodinium muscatinei and Elliptochloris marina, symbionts found within the aggregating sea anemone Anthopleura elegantissima.

There is a growing body of literature using transcriptomic data to study how tropical cnidarians and their photosynthetic endosymbionts respond to environmental stressors and participate in metabolic exchange. Despite these efforts, our understanding of how essential genes function to facilitate symbiosis establishment and maintenance remains limited. The inclusion of taxonomically and ecologically diverse endosymbionts will enhance our understanding of these interactions. Here we characterize the transcriptomes of two very different symbionts found within the temperate sea anemone Anthopleura elegantissima: the chlorophyte Elliptochloris marina and the dinoflagellate Symbiodinium muscatinei. We use a multi-level approach to assess the diversity of genes found across S. muscatinei and E. marina transcriptomes, and compare their overall protein domains with other dinoflagellates and chlorophytes. Our analysis identified several genes that are potentially involved in mitigating stress response (e.g., heat shock proteins pathways for mediating reactive oxygen species) and metabolic exchange (e.g., ion transporters). Finally, we show that S. muscatinei and other Symbiodinium strains are equipped with a high salt peridinin-chl-protein (HSPCP) gene previously identified only in free-living dinoflagellates. The addition of these transcriptomes to the cnidarian-symbiont molecular toolkit will aid in understanding how these vitally important symbiotic relationships are established and maintained across a variety of environmental conditions.

Simulating Fine-Scale Marine Pollution Plumes for Autonomous Robotic Environmental Monitoring.

Marine plumes exhibit characteristics such as intermittency, sinuous structure, shape and flow field coherency, and a time varying concentration profile. Due to the lack of experimental quantification of these characteristics for marine plumes, existing work often assumes marine plumes exhibit behavior similar to aerial plumes and are commonly modeled by filament based Lagrangian models. Our previous field experiments with Rhodamine dye plumes at Makai Research Pier at Oahu, Hawaii revealed that marine plumes show similar characteristics to aerial plumes qualitatively, but quantitatively they are disparate. Based on the field data collected, this paper presents a calibrated Eulerian plume model that exhibits the qualitative and quantitative characteristics exhibited by experimentally generated marine plumes. We propose a modified model with an intermittent source, and implement it in a Robot Operating System (ROS) based simulator. Concentration time series of stationary sampling points and dynamic sampling points across cross-sections and plume fronts are collected and analyzed for statistical parameters of the simulated plume. These parameters are then compared with statistical parameters from experimentally generated plumes. The comparison validates that the simulated plumes exhibit fine-scale qualitative and quantitative characteristics similar to experimental plumes. The ROS plume simulator facilitates future evaluations of environmental monitoring strategies by marine robots, and is made available for community use.

Utilization of hypofractionated radiotherapy in treatment of glioblastoma multiforme in elderly patients not receiving adjuvant chemoradiotherapy: A National Cancer Database Analysis.

To assess the utilization and outcomes of adjuvant monotherapy with hypofractionated radiation (RT) among elderly patients not receiving traditional adjuvant chemoradiotherapy (cRT) for glioblastoma multiforme (GBM). A retrospective analysis using the National Cancer Data Base with GBM patients aged 65 years or older treated between 2005 and 2012 was conducted. Patients who underwent hypofractionated RT (40 Gy), conventional RT (60 Gy), chemotherapy, or best supportive care alone were included. Statistical methods included logistic regression for utilization and Cox regression for survival analysis. A total of 9556 patients were analyzed. On multivariate analysis (compared to those receiving conventional RT), patients more likely to be treated with hypofractionated RT were older (75-84 years old OR 2.05; p < 0.01 and ≥ 85 years old OR 3.32; p < 0.01), with a Charlson/Deyo score of 2 or higher (OR 1.80; p = 0.05), from communities > 50 miles from their treatment facility (50-100 miles OR 8.03; p < 0.01 and > 100 miles OR 7.16; p < 0.01), treated at an Academic/Research facility (OR 2.85; p = 0.04), and diagnosed between 2011 and 2012 (OR 4.15; p < 0.01). On Cox regression, hypofractionated RT (HR 0.65; p < 0.01), conventional RT (HR 0.60; p < 0.01), and chemotherapy alone (HR 0.69; p < 0.01) were all associated with decreased risk of death compared to no adjuvant therapy. Among patients receiving adjuvant treatment, utilization of hypofractionated RT increased from 7 to 19% during the study period. Among elderly patients with GBM not receiving cRT, the utilization of adjuvant monotherapy with hypofractionated RT has increased over time. Retrospective evidence suggests it may be better than best supportive care alone and as good as conventionally fractionated RT alone.

IL-6 variant is associated with metastasis in breast cancer patients.

INTRODUCTION: Although tumor metastases remain significant drivers of mortality, the genetic factors that increase the risks of metastases are not fully identified. Interleukin 6 (IL-6) has emerged as an important factor in breast cancer progression with IL-6 single nucleotide polymorphism (SNP) variants shown to affect survival. We hypothesized that SNPs of the IL-6 promoter at rs1800795 in breast cancer patients are associated with distant metastases. METHODS: We performed an initial case-control study using Vanderbilt University Medical Center's BioVU, a genomic biobank linked to de-identified electronic medical records in the Synthetic Derivative database, to identify germline SNPs that may predict the development of metastatic disease to any site from any solid tumor including breast cancer. We identified a SNP in IL-6: rs1800795 to be of significance and evaluated this finding using a separate, matched-pair cohort of breast cancer patients with and without metastases from The Ohio State University Wexner Medical Center. RESULTS: The initial study suggested that GG relative to CG at rs1800795 (OR 1.52; 95% CI 1.14-2.02; p = 0.004) was significantly associated with the development of metastases. This association was also observed in the Ohio State University cohort (OR 2.23; 95% CI 1.06-4.71; p = 0.001). There were no significant relationships between rs1800795 status and any patient or tumor characteristics, including estrogen receptor status. CONCLUSIONS: These findings suggest that GG SNP at IL-6: rs1800795 may indicate an increased risk of metastasis of primary breast cancer. Further studies in larger population sets are warranted as advanced screening and prophylactic intervention might be employed in GG carriers.

Brachytherapy Improves Survival in Stage III Endometrial Cancer With Cervical Involvement.

PURPOSE: To evaluate the survival benefit of adding vaginal brachytherapy (BT) to pelvic external beam radiation therapy (EBRT) in women with stage III endometrial cancer. METHODS AND MATERIALS: The National Cancer Data Base was used to identify patients with stage III endometrial cancer from 2004 to 2013. Only women who received adjuvant EBRT were analyzed. Women were grouped according to receipt of BT. Logistic regression modeling was used to identify predictors of receiving BT. Log-rank statistics were used to compare survival outcomes. Cox proportional hazards modeling was used to evaluate the effect of BT on survival. A propensity score-matched analysis was also conducted among women with cervical involvement. RESULTS: We evaluated 12,988 patients with stage III endometrial carcinoma, 39% of whom received EBRT plus BT. Women who received BT were more likely to have endocervical or cervical stromal involvement (odds ratios 2.03 and 1.77; P<.01, respectively). For patients receiving EBRT alone, the 5-year survival was 66% versus 69% with the addition of BT at 5 years (P<.01). Brachytherapy remained significantly predictive of decreased risk of death (hazard ratio 0.86; P<.01) on multivariate Cox regression. The addition of BT to EBRT did not affect survival among women without cervical involvement (P=.84). For women with endocervical or cervical stromal invasion, the addition of BT significantly improved survival (log-rank P<.01). Receipt of EBRT plus BT was associated with improved survival in women with positive and negative surgical margins, and receiving chemotherapy did not alter the benefit of BT. Propensity score-matched analysis results confirmed the benefit of BT among women with cervical involvement (hazard ratio 0.80; P=.01). CONCLUSIONS: In this population of women with stage III endometrial cancer the addition of BT to EBRT was associated with an improvement in survival for women with endocervical or cervical stromal invasion.

Multi-institutional experience of stereotactic body radiotherapy for large (≥5 centimeters) non-small cell lung tumors.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is the standard of care for patients with nonoperative, early-stage non-small cell lung cancer (NSCLC) measuring < 5 cm, but its use among patients with tumors measuring ≥5 cm is considerably less defined, with the existing literature limited to small, single-institution reports. The current multi-institutional study reported outcomes evaluating the largest such population reported to date. METHODS: Clinical/treatment characteristics, outcomes, toxicities, and patterns of failure were assessed in patients with primary NSCLC measuring ≥5 cm without evidence of distant/lymph node metastasis who underwent SBRT using ≤5 fractions. Statistics included Kaplan-Meier survival analyses and univariate/multivariate Cox proportional hazards models. RESULTS: A total of 92 patients treated from 2004 through 2016 were analyzed from 12 institutions. The median follow-up was 12 months (15 months in survivors). The median age and tumor size among the patients were 73 years (range, 50-95 years) and 5.4 cm (range, 5.0-7.5 cm), respectively. The median dose/fractionation was 50 Gray/5 fractions. The actuarial local control rates at 1 year and 2 years were 95.7% and 73.2%, respectively. The disease-free survival rate was 72.1% and 53.5%, respectively, at 1 year and 2 years. The 1-year and 2-year disease-specific survival rates were 95.5% and 78.6%, respectively. The median, 1-year, and 2-year overall survival rates were 21.4 months, 76.2%, and 46.4%, respectively. On multivariate analysis, lung cancer history and pre-SBRT positron emission tomography maximum standardized uptake value were found to be associated with overall survival. Posttreatment failures were most commonly distant (33% of all disease recurrences), followed by local (26%) and those occurring elsewhere in the lung (23%). Three patients had isolated local failures. Grade 3 to 4 toxicities included 1 case (1%) and 4 cases (4%) of grade 3 dermatitis and radiation pneumonitis, respectively (toxicities were graded according to the Common Terminology Criteria for Adverse Events [version 4.0]). Grades 2 to 5 radiation pneumonitis occurred in 11% of patients. One patient with a tumor measuring 7.5 cm and a smoking history of 150 pack-years died of radiation pneumonitis. CONCLUSIONS: The results of the current study, which is the largest study of patients with NSCLC measuring ≥5 cm reported to date, indicate that SBRT is a safe and efficacious option. Cancer 2017;123:688-696. © 2016 American Cancer Society.

Socioeconomic and Ethnic Disparities in Periocular Cutaneous Malignancies.

Cutaneous malignancies make up the majority of periocular tumors diagnosed and treated by ophthalmologists. In this review, we examine literature regarding ethnic and socioeconomic disparities in incidence and clinical outcomes of the three most common cutaneous periocular tumors: basal cell carcinoma, squamous cell carcinoma, and melanoma. In all three tumor types, the literature shows an increased incidence among two groups: those with lightly pigmented skin and those of higher socioeconomic status. While incidence is high in these groups, clinical outcomes for these patients tend to be good. Those with lower socioeconomic status and ethnic minorities, on the other hand, have a low incidence but are more likely to have poor clinical outcomes. These disparities are likely the result of both biologic and behavioral differences between patients and could provide opportunities for intervention to change risk perception and improve outcomes.

Symbiotic state influences life-history strategy of a clonal cnidarian.

Along the North American Pacific coast, the common intertidal sea anemone Anthopleura elegantissima engages in facultative, flexible symbioses with Symbiodinium muscatinei (a dinoflagellate) and Elliptochloris marina (a chlorophyte). Determining how symbiotic state affects host fitness is essential to understanding the ecological significance of engaging in such flexible relationships with diverse symbionts. Fitness consequences of hosting S. muscatinei, E. marina or negligible numbers of either symbiont (aposymbiosis) were investigated by measuring growth, cloning by fission and gonad development after 8.5-11 months of sustained exposure to high, moderate or low irradiance under seasonal environmental conditions. Both symbiotic state and irradiance affected host fitness, leading to divergent life-history strategies. Moderate and high irradiances led to a greater level of gonad development in individuals hosting E. marina, while high irradiance and high summer temperature promoted cloning in individuals hosting S. muscatinei and reduced fitness of aposymbiotic anemones. Associating with S. muscatinei may contribute to the success of A. elegantissima as a spatial competitor on the high shore: (i) by offsetting the costs of living under high temperature and irradiance conditions, and (ii) by promoting a high fission rate and clonal expansion. Our results suggest that basic life-history characteristics of a clonal cnidarian can be affected by the identity of the endosymbionts it hosts.

Relationships between host and symbiont cell cycles in sea anemones and their symbiotic dinoflagellates.

The processes by which cnidarians and their algal endosymbionts achieve balanced growth and biomass could include coordination of host and symbiont cell cycles. We evaluated this theory with natural populations of sea anemones hosting symbiotic dinoflagellates, focusing on the temperate sea anemone Anthopleura elegantissima symbiotic with Symbiodinium muscatinei in Washington State, USA, and the tropical anemone Stichodactyla helianthus associating with unknown Symbiodinium spp. in Belize. By extruding symbiont-containing gastrodermal cells from the relatively large tentacles of these species and using nuclear staining and flow cytometry, we selectively analyzed cell cycle distributions of the symbionts and the host gastrodermal cells that house them. We found no indications of diel synchrony in host and symbiont G2/M phases, and we observed evidence of diel periodicity only in Symbiodinium spp. associated with S. helianthus but not in the anemone itself. Seasonally, S. muscatinei showed considerable G2/M phase variability among samples collected quarterly over an annual period, while the G2/M phase of its host varied much less. Within samples taken at different times of the year, correlations between host and symbiont G2/M phases ranged from very weakly to very strongly positive, with significant correlations in only half of the samples (two of four A. elegantissima samples and one of two S. helianthus samples). Overall, the G2/M phase relationships across species and sampling periods were positive. Thus, while we found no evidence of close cell cycle coupling, our results suggest a loose, positive relationship between cell cycle processes of the symbiotic partners.

Exogenous prenatal corticosterone exposure mimics the effects of prenatal stress on adult brain stress response systems and fear extinction behavior.

Exposure to early-life stress is a risk factor for the development of cognitive and emotional disorders later in life. We previously demonstrated that prenatal stress (PNS) in rats results in long-term, stable changes in central stress-response systems and impairs the ability to extinguish conditioned fear responding, a component of post-traumatic stress disorder (PTSD). Maternal corticosterone (CORT), released during prenatal stress, is a possible mediator of these effects. The purpose of the present study was to investigate whether fetal exposure to CORT at levels induced by PNS is sufficient to alter the development of adult stress neurobiology and fear extinction behavior. Pregnant dams were subject to either PNS (60 min immobilization/day from ED 14-21) or a daily injection of CORT (10mg/kg), which approximated both fetal and maternal plasma CORT levels elicited during PNS. Control dams were given injections of oil vehicle. Male offspring were allowed to grow to adulthood undisturbed, at which point they were sacrificed and the medial prefrontal cortex (mPFC), hippocampus, hypothalamus, and a section of the rostral pons containing the locus coeruleus (LC) were dissected. PNS and prenatal CORT treatment decreased glucocorticoid receptor protein levels in the mPFC, hippocampus, and hypothalamus when compared to control offspring. Both treatments also decreased tyrosine hydroxylase levels in the LC. Finally, the effect of prenatal CORT exposure on fear extinction behavior was examined following chronic stress. Prenatal CORT impaired both acquisition and recall of cue-conditioned fear extinction. This effect was additive to the impairment induced by previous chronic stress. Thus, these data suggest that fetal exposure to high levels of maternal CORT is responsible for many of the lasting neurobiological consequences of PNS as they relate to the processes underlying extinction of learned fear. The data further suggest that adverse prenatal environments constitute a risk factor for PTSD-like symptomatology, especially when combined with chronic stressors later in life.

Symbiont physiology and population dynamics before and during symbiont shifts in a flexible algal-cnidarian symbiosis.

For cnidarians that can undergo shifts in algal symbiont relative abundance, the underlying algal physiological changes that accompany these shifts are not well known. The sea anemone Anthopleura elegantissima associates with the dinoflagellate Symbiodinium muscatinei and the chlorophyte Elliptochloris marina, symbionts with very different tolerances to light and temperature. We compared the performance of these symbionts in anemones maintained in an 8-11.5 month outdoor common garden experiment with simulated intertidal conditions and three levels of shading (2, 43, and 85% ambient irradiance). Symbiont densities, mitotic indices, photophysiology and pigments were assessed at three time points during the summer, a period of high irradiance and solar heating during aerial exposure. Whereas S. muscatinei was either neutrally or positively affected by higher irradiance treatments, E. marina responded mostly negatively to high irradiance. E. marina in the 85% irradiance treatment exhibited significantly reduced Pmax and chlorophyll early in the summer, but it was not until nearly 3 months later that a shift in symbiont relative abundance toward S. muscatinei occurred, coincident with bleaching. Symbiont densities and proportions remained largely stable in all other treatments over time, and displacement of S. muscatinei by E. marina was not observed in the 2% irradiance treatment despite the potentially better performance of E. marina. While our results support the view that rapid changes in symbiont relative abundance are typically associated with symbiont physiological dysfunction and bleaching, they also show that significant temporal lags may occur between the onset of symbiont stress and shifts in symbiont relative abundances.

Effects of chronic plus acute prolonged stress on measures of coping style, anxiety, and evoked HPA-axis reactivity.

Exposure to psychological trauma is the precipitating factor for PTSD. In addition, a history of chronic or traumatic stress exposure is a predisposing risk factor. We have developed a Chronic plus Acute Prolonged Stress (CAPS) treatment for rats that models some of the characteristics of stressful events that can lead to PTSD in humans. We have previously shown that CAPS enhances acute fear responses and impairs extinction of conditioned fear. Further, CAPS reduced the expression of glucocorticoid receptors in the medial prefrontal cortex. In this study we examined the effects of CAPS exposure on behavioral stress coping style, anxiety-like behaviors, and acute stress reactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Male Sprague-Dawley rats were exposed to CAPS treatment, consisting of chronic intermittent cold stress (4 °C, 6 h/day, 14 days) followed on day 15 by a single 1-h session of sequential acute stressors (social defeat, immobilization, swim). After CAPS or control treatment, different groups were tested for shock probe defensive burying, novelty suppressed feeding, or evoked activation of adrenocorticotropic hormone (ACTH) and corticosterone release by an acute immobilization stress. CAPS resulted in a decrease in active burying behavior and an increase in immobility in the shock probe test. Further, CAPS-treated rats displayed increases in the latency to feed in the novelty suppressed feeding test, despite an increase in food intake in the home cage. CAPS treatment also reduced the HPA response to a subsequent acute immobilization stress. These results further validate CAPS treatment as a rat model of relevance to PTSD, and together with results reported previously, suggest that CAPS impairs fear extinction, shifts coping behavior from an active to a more passive strategy, increases anxiety, and alters HPA reactivity, resembling many aspects of human PTSD.

Thicker host tissues moderate light stress in a cnidarian endosymbiont.

The susceptibility of algal-cnidarian holobionts to environmental stress is dependent on attributes of both host and symbiont, but the role of the host is often unclear. We examined the influence of the host on symbiont light stress, comparing the photophysiology of the chlorophyte symbiont Elliptochloris marina in two species of sea anemones in the genus Anthopleura. After 3 months of acclimation in outdoor tanks, polyp photoprotective contraction behavior was similar between the two host species, but photochemical efficiency was 1.5 times higher in A. xanthogrammica than in A. elegantissima. Maximum relative electron transport rates, derived from rapid light curves, were 1.5 times higher in A. xanthogrammica than in A. elegantissima when symbionts were inside intact tissues, but were not significantly different between host species upon removal of outer (epidermis and mesoglea) tissue layers from symbiont-containing gastrodermal cells. Tissues of A. xanthogrammica were 1.8 times thicker than those of A. elegantissima, with outer tissue layers attenuating 1.6 times more light. We found no significant differences in light absorption properties per unit volume of tissue, confirming the direct effect of tissue thickness on light attenuation. The thicker tissues of A. xanthogrammica thus provide a favorable environment for E. marina - a relatively stress-susceptible symbiont - and may explain its higher prevalence and expanded range in A. xanthogrammica along the Pacific coast of North America. Our findings also support a photoprotective role for thicker host tissues in reef corals that has long been thought to influence variability in bleaching susceptibility among coral taxa.

Early adolescence as a critical window during which social stress distinctly alters behavior and brain norepinephrine activity.

Many neural programs that shape behavior become established during adolescence. Adverse events at this age can have enduring consequences for both adolescent and adult mental health. Here we show that repeated social stress at different stages of adolescent development differentially affects rat behavior and neuronal activity. Early-adolescent (PND 28, EA), mid-adolescent (PND 42, MA), and adult (PND 63) rats were subjected to resident-intruder social stress (7 days) and behavior was examined 24-72 h later. In EA rats selectively, resident-intruder stress increased proactive responses in the defensive burying and forced swim tests. In adult rats, resident-intruder stress decreased burying behavior regardless of whether the animal was stressed as an adult or during early adolescence. As the locus coeruleus (LC)-norepinephrine system has been implicated in proactive defense behaviors, LC neuronal activity was quantified in separate cohorts. Stressed EA rats had elevated spontaneous LC discharge rates and diminished responses to sensory stimuli compared with controls. Microinjection of a CRF antagonist into the LC selectively inhibited neurons of stressed EA rats, suggesting that EA social stress induces tonic CRF release onto LC neurons, shifting the mode of discharge to an activated state that promotes active defensive behaviors. In all adult groups, resident-intruder stress resulted in an increased phasic response to sensory stimuli with no change in spontaneous rates. MA was a transition period during which social stress did not affect behavior or LC activity. The results suggest that social stress interacts with the brain norepinephrine system to regulate defensive strategies in an age-dependent manner.