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Purpose/Objective(s) Optimal control of brain metastases (BM) from renal cell carcinoma (RCC) with stereotactic radiosurgery (SRS) is critical as tyrosine kinase inhibitors (TKI) and immunotherapy has significantly prolonged overall survival (OS), emphasizing the importance of minimizing potential morbidity from treatment-associated edema. Clinically, we have observed that RCC BM-associated edema seems to be less prominent when VEGF-targeted agents (VEGFi) such as axitinib are administered contemporaneously with SRS. We therefore investigated the role of VEGFi in intracranial edema reduction in pts treated with SRS. Materials/Methods We conducted a single institution retrospective analysis of all clear cell or unknown RCC pts with BM treated with SRS from 2013 onwards. We excluded non-clear cell RCC, lack of post-SRS imaging, and failure to complete SRS. The SRS plus VEGFi cohort was defined as VEGFi within 6 months of SRS. Volumetric data was obtained from SRS plans, edema was contoured on MR Brain T2 Flair, and paired t-test was performed. Multivariate analysis for OS performed with the Cox proportional hazards model. Results We identified 38 pts who received 78 courses of SRS + VEGFi and 18 pts who received 29 courses of SRS alone. For the SRS + VEGFi and SRS groups, median OS was 4.1y and 6.0y, median SRS dose was 21 Gy and 27 Gy with comparable pre-SRS steroid use of 52% and 57% (HR 0.51, P = 0.200) and baseline neurologic symptoms 50% and 74% (HR 0.943, P = 0.904), respectively. Among the SRS + VEGFi group, the mean intact tumor volume decreased from pre-SRS 1.89cc to 0.42cc at 6m post-SRS, compared to a decrease from 1.82cc to 1.28cc in the SRS group. Edema volume decreased from 17.65cc to 3.28cc in the SRS + VEGFi group with an increase from pre-SRS 5.78cc to 6.39cc at 6mo post-SRS in the SRS alone group (95% CI -3.67, 1.15, P = 0.154). Conclusion Despite similar pre-SRS steroid use and increased edema volume, VEGFi appeared to improve post-SRS edema with a notable reduction of neurological symptoms. Our data suggest VEGFi may offer symptomatic benefit for significant peritumoral edema even without overt disease progression, and that re-challenge or continuation of VEGFi with SRS should be considered in such patients.

Assessing the sensitivity of groundwater systems to hydroclimate variability is critical to sustainable management of the water resources of Guam, US territory. We assess spatial and temporal variability of isotopic and geochemical compositions of vadose and phreatic groundwater sampled from cave drip sites and production wells, respectively, to better understand the vulnerability of the freshwater lens on Guam to variability in hydroclimate. We independently evaluate the existing conceptual model of the Northern Guam Lens Aquifer that is largely based on physical, as opposed to geochemical, observations. Sampling was conducted from 2008 to 2015, over which rainfall gradually increased. Major ion geochemistry and Sr isotope values of groundwater show varying influence from soil, limestone bedrock, and seawater. Geochemical modeling that can explain spatial variability in groundwater Na+ and Mg2+ concentrations and Sr/Ca and 87Sr/86Sr values indicates that groundwater compositions are dominantly controlled by mixing of freshwater with seawater and water-rock interaction. Differences between amount-weighted annual average precipitation δ18O values and groundwater δ18O values indicate a recharge bias toward the wet season, consistent with other tropical carbonate island aquifer settings. Intra- and inter-annual variations in Na+ concentrations and δ18O values in groundwater reflect sensitivity of recharge to seasonal variations in rainfall amount and changes in annual rainfall amounts. Our results indicate the influence of multiple modes of recharge on groundwater compositions and spatial variability in the sensitivity of groundwater to seawater mixing. This sensitivity of the freshwater lens points to the vulnerability of groundwater resources to changes in recharge associated with climate, land-use change, and increases in population.

Attention-deficit/hyperactivity disorder (ADHD) rating scales typically provide normative tables arranged according to child age, child gender, and type of informant, which facilitates addressing the fifth edition of the Diagnostic and Statistical Manual of Mental Health Disorders developmental deviance requirement for diagnosing ADHD. Missing, however, is any consideration of the gender of the informant. The purpose of this paper was to conduct an exploratory examination of informant gender via secondary analyses of a large data set used to standardize the ADHD Rating Scale-5. Two (informant gender) by two (child gender) ANOVAs were conducted separately for parents and teachers using inattention (IN) symptoms, hyperactive-impulsive (HI) symptoms, the total impairment score related to IN, and the total impairment score for HI as dependent variables. Results showed that female parents rated male children significantly higher on both IN symptoms and impairment related to IN than did male parents. Female teacher ratings were also significantly higher than male teacher ratings for male children in terms of HI symptoms and with respect to impairment ratings related to both HI and IN. A significantly higher percentage of female parents (7.7%) identified male children as being at risk for ADHD relative to male parents (4.1%). This same pattern emerged for female teachers (11.9%) versus male teachers (5.3%). Such results suggest that informant gender may play a clinically meaningful role in assessing ADHD in children and adolescents, which is consistent with the developmental literature addressing gender stereotypes in children. Future research is needed to determine whether similar informant gender differences exist in other rating scale measures of ADHD. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Context Pituitary carcinoma is a rare and aggressive malignancy with a poor prognosis and few effective treatment options. Case A 35-year-old woman presented with an aggressive ACTH-secreting pituitary adenoma that initially responded to concurrent temozolomide and capecitabine prior to metastasizing to the liver. Following treatment with ipilimumab and nivolumab, the tumor volume of the dominant liver metastasis reduced by 92%, and the recurrent intracranial disease regressed by 59%. Simultaneously, her plasma ACTH level decreased from 45,550 pg/mL to 66 pg/mL. Molecular Evaluation Both prospective clinical sequencing with Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets and retrospective whole-exome sequencing were performed to characterize the molecular alterations in the chemotherapy-naive pituitary adenoma and the temozolomide-resistant liver metastasis. The liver metastasis harbored a somatic mutational burden consistent with alkylator-induced hypermutation that was absent from the treatment-naive tumor. Resistance to temozolomide treatment, acquisition of new oncogenic drivers, and subsequent sensitivity to immunotherapy may be attributed to hypermutation. Conclusion Combination treatment with ipilimumab and nivolumab may be an effective treatment in pituitary carcinoma. Clinical sequencing of pituitary tumors that have relapsed following treatment with conventional chemotherapy may identify the development of therapy-induced somatic hypermutation, which may be associated with treatment response to immunotherapy.

PURPOSE/OBJECTIVE(S) Limited data exist regarding the effect of radiotherapy (RT) and poly (ADP-ribose) polymerase inhibition (PARPi) for brain metastases (BM). However, RT is known to elevate PARP levels and thus, PARPi may have radiosensitizing effects. We hypothesize that among BRCA germline mutant (BRCAgm) patients, receipt of adjuvant and/or concurrent PARPi and RT for BM delays time to intracranial failure. MATERIALS/METHODS With IRB approval, we reviewed BRCAgm patients and BM who received oral PARPi and RT-whole brain (WBRT, 30 Gy/10 fractions) or stereotactic radiosurgery (SRS, 21-27 Gy/1-3 fractions)-between 2010-2020. Of 33 patients identified, 12 were excluded for any progression on PARPi, requiring salvage RT; and 6 were excluded for > 2 month interval between RT and adjuvant PARPi. We stratified into groups based on timing of PARPi relative to RT: 1) Patients on PARPi prior to RT and maintained on PARPi thereafter ("Concurrent"); and 2) Patients who initiated PARPi after completion of RT ("Adjuvant"). Primary outcomes were intracranial progression-free survival (PFS) and overall survival (OS) with estimates generated using the Kaplan-Meier method. Secondary outcome was toxicity. BrainGPA was used to predict median survival in patients with eligible histologies. RESULTS Fifteen patients (female, N = 12; male, N = 3) met inclusion criteria. Median (range) KPS was 80 (70-90), and age at radiation was 50 years (32-76). Median follow-up was 10.9 months (3.1-27.8). Sixty-three percent had breast cancer (N = 10) and 87% received Olaparib (N = 13). Among 8 concurrent patients, 5 received SRS and 3 received WBRT; median intracranial PFS was 5.7 months (1.9-17.5) and median OS was 10.4 months (3.1-17.5). Among 7 adjuvant patients, 4 received SRS and 3 WBRT; median intracranial PFS was 9.9 months (4.0-18.2) and median OS was 10.9 months (4.0-28.4). Median time to PARPi after RT was 2 weeks. Of 10 patients with histologies eligible for BrainGPA calculation, 90% exceeded the predicted median survival. There were no cases of grade ≥3 toxicity, including radionecrosis. CONCLUSION In this small series of BRCAgm patients, RT with concurrent and/or adjuvant PARPi for BM was feasible and safe. Several patients had long intervals of intracranial PFS suggestive of heightened sensitivity to RT particularly with adjuvant PARPi. Future prospective studies in larger cohorts are warranted to determine the optimal timing of PARPi relative to brain RT.

Because accurate identification of ADHD is a necessary first step to guide the selection and implementation of evidence-based treatments, this chapter focuses on the assessment and diagnosis of ADHD in children. It begins with a brief review of the historical unfolding of this disorder, from its earliest formal beginnings to its current appearance in the health care field as ADHD. Presented next is a brief overview of its epidemiology, etiology, and developmental course. This is followed by a detailed description of the way in which ADHD presents itself clinically, in terms of the variability in its primary symptom presentation, its co-occurring features, and its impact on daily functioning. Against this background, this chapter concludes with a detailed discussion of evidence-based guidelines for diagnosing ADHD, including suggestions for making differential diagnoses and for handling discrepancies across different sources of evaluation data.

PURPOSE: The presence of brain metastases (BM) in patients with non-seminomatous germ cell tumor (NSGCT) is associated with poor prognosis. While radiation therapy (RT) is an important treatment for patients with NSGCT BM, there is a paucity of data on the optimal regimen. We sought to investigate the impact of RT on clinical outcomes in patients with NSGCT BM. METHODS: Patients with NSGCT BM who received RT at our institution from 2002–2017 were included. Sixty-three consecutive patients were identified. Clinical factors associated with intracranial control (ICC) and overall survival (OS) were evaluated using Cox regression analysis and Kaplan Meier method. RESULTS: Median age was 31 years and number of BM was 3. Fifteen patients presented with BM at diagnosis, while 48 developed BM at a median time of 8.4 months from diagnosis. At a median follow-up of 3.6 years, ICC and OS were 39.7% and 30.1%. On multivariate analysis, ICC (hazard ratio [HR]=0.93, p=0.03) and OS (HR=0.93, p=0.005) were both significantly associated with biologically effective dose (BED) of RT. The 4-year OS of patients who received BED

Research examining the influence of parent material on soil and landscape development is limited in dryland environments. In volcanic soils, most studies examining soil development and succession have been conducted in humid environments, where weathering occurs rapidly. This study was conducted in a semi-arid environment to examine the influence of volcanic parent material morphology on soil development and ecohydrologic properties that may regulate primary succession. Four study sites were selected across young (~ 2.0 ka) and old (~ 12.1 ka) end members of two different parent materials (cinder cones and pahoehoe lava flows). We hypothesized that soils and associated hydraulic properties would evolve more rapidly on the cinder cones compared to the pahoehoe flows owing to greater surface area on the cinder. For each site, we quantified plant cover, soil organic matter, bulk density, texture, soil water retention, and hydraulic conductivity. The old cinder cone soils accumulated approximately 9% soil organic matter and increased in silt plus clay fraction by 23% relative to the young soil. This increased water retention and decreased hydraulic conductivity. Similarly, plant cover increased by 47%. The old pahoehoe site remained dominated by unweathered basalt, where silty eolian material accumulated preferentially in crevices. Soil organic matter and silt plus clay fraction increased by 18% and 49% respectively in old pahoehoe soils, resulting in increased water retention but little change in hydraulic conductivity. Plants were restricted to crevices and cover increased by only 34%. We observed the cinder cone sites had extensive soil and plant community development from the young to old sites. The pahoehoe soils and plant communities established earlier than on cinder cones, but showed only modest functional changes between young and old sites. The combined characterization of soil development, hydraulic properties, and plant community dynamics highlights potential ecohydrologic mechanisms controlling successional processes in young semi-arid landscapes.

This essay responds to Carol A. Newsom's recent call for finer-grained studies of particular formulations of the moral self and agency in biblical and related Second Temple texts in two ways: first, drawing on cognitive linguistic research of George Lakoff and Mark Johnson, it highlights the embodied metaphorical quality of all forms of self-conception and self-representation; second, it examines the network of conceptual metaphors of the self in the Hebrew text of Esther, especially as they speak to questions of subjective agency. Although the book of Esther draws several of its conceptual metaphors from other Hebrew biblical texts (e.g. the heart as self, the self as fillable, the self filled with wine, the self filled with heat, heat abating or dissipating from the self, etc.), it deploys them in such a way as to call into question any delusion of self-control and agency on the part of its royal patriarchal subjects, Ahasuerus and Haman. Instead of affirming agency, these metaphors conceive of the self as easily manipulated and unsettled, thereby revealing a highly insecure subjectivity that is never fully in possession of itself.