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BACKGROUND: Modulation of glucocorticoid receptor (GR) activity in tumor cells enhances chemotherapy efficacy. We evaluated the selective GR modulator relacorilant plus nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who had received at least 2 prior therapy lines. PATIENTS AND METHODS: In this open-label, single-arm, phase III study, patients received once-daily oral relacorilant (100 mg, titrated to 150 mg in 25 mg increments/cycle) and nab-paclitaxel (80 mg/m2) on days 1, 8, and 15 of 28-day cycles. The primary efficacy endpoint was objective response rate (ORR) by blinded independent central review. Progression-free survival (PFS), overall survival (OS), target gene modulation, and safety were also assessed. RESULTS: Of 43 patients enrolled, 31 were evaluable for ORR (12 did not reach first postbaseline radiographic assessment). An interim analysis to assess whether ORR was ≥10% showed no confirmed responses and the study was discontinued. Two (6.5%) patients attained unconfirmed partial responses and 15 (48.4%) had stable disease. Fourteen of 31 (45.2%) patients had reductions in target lesion size, despite prior nab-paclitaxel exposure in 12 of the 14. Median PFS and OS were 2.4 months (95% CI, 1.4-4.2) and 3.9 months (95% CI, 2.8-4.9), respectively. The most common adverse events were fatigue and nausea. RNA analysis confirmed that relacorilant plus nab-paclitaxel suppressed 8 cortisol target genes of interest. CONCLUSION: Relacorilant plus nab-paclitaxel showed modest antitumor activity in heavily pretreated patients with mPDAC, with no new safety signals. Studies of this combination in other indications with a high unmet medical need are ongoing.

INTRODUCTION 2098 I. THE NEW COORDINATION PROBLEMS 2102 A. Key Features of Lending and Capital Structure 2103 1. Leveraged Loans, CLOs, and Pioneering Women 2103 2. Predominance of Secured Claims [...], The large companies that currently file for Chapter 11 look very different from the typical Chapter 11 cases of the past. The liability side of debtors' balance sheets is much more complex and now consists primarily of secured rather than unsecured obligations. Many firms that might once have borrowed on a secured basis from a bank and on an unsecured basis from bondholders now have first and second liens instead. Leveraged loans have further contributed to the prevalence of secured debt. While these developments are beneficial in many respects, they have exacerbated two serious problems in Chapter 11. The first is the unusually high variability in outcomes in large cases as lenders enter and exit the lending syndicates and as debtors and creditors exploit loopholes in the credit documents through "uptiering" and "dropdown" or "trapdoor" transactions. Second is a growing perception that insiders benefit from Chapter 11 and outsiders often do not. An unfortunate irony is that efforts (such as restructuring support agreements) to reduce the first problem--uncertainty--often exacerbate the second--insider control. Part I of the Article recounts the shift in debtors' capital structure due to the new financing techniques, highlighting a surprising feature of the emergence of the leveraged loan and CLO markets: women playing an unusually prominent role. Part II explores the close, though partial, relationship between private equity funds and these recent developments. The final part considers a series of potential solutions and interventions for addressing the downsides of the new financing techniques. The Part advocates an incrementalist approach while warning that, unless the perception that Chapter 11 is rigged in favor of insiders is addressed, pressure may build for more radical reform.

Learning Objective: To describe on-line resources and strategy used by EM residents prior to performing a simulated dental nerve block including search terms, sources, and time.Background: EM physicians are called to perform infrequently done procedures, often using on-line resources to prepare.Objectives: To describe on-line resources used by EM residents prior to performing a simulated nerve block.Methods: Prospective, observational study of EM residents during a simulation workshop. Subjects were provided a visual prompt of an abscess and given 15 minutes to use on-line resources, then demonstrated the dental nerve block on a skull model. Video screen shots were recorded and data collected including search time, strategy, type and number of resources used. Subjects were observed performing the block and given credit if performed correctly. Residents answered a survey about previous experience, preferred resources and confidence in performing the procedure.Results: 26 residents participated. The median search time was 4 minutes, 5 seconds. 57.7 % of subjects used a general search term as opposed to a specific procedure. Sites included You-Tube 69%, Google Images 53.8%, WikiEM 42%, EMRA 15%, and UpToDate 11.5%. 61.5% used 2 links. 50% used a combination of written and video material whereas 23% used video material alone. 81.8% performed the block correctly. Survey results: 42% of residents reported having done a dental block on a patient with 3.8% reporting previous training. 50% reviewed both written and video sources with 76% of respondents finding video sources more helpful. 96.2% residents felt they had adequate time to review the procedure. Confidence in ability to perform the procedure after review varied: 3.8% very confident; 46% confident; 23% neutral and 27% somewhat confident.Conclusions: YouTube was the most frequently used resource in researching how to perform a dental nerve block. The majority of residents applied previous experience and just in time learning to correctly identify injection landmarks on a simulated model. Having a centralized video bank may decrease prep time for infrequently performed procedure.

If assessment is the purpose of testing, open-book tests may defeat the purpose. However, a goal of education is to build knowledge, and based on the literature, open-book tests may not be inferior to closed-book tests in promoting long-term retention of information. Participants studied Swahili-English pairs and either re-studied or took an initial quiz, which was cued recall or recognition in an open-book or closed-book format. One week later, the final closed-book recognition test showed higher performance in the quizzed conditions than in the study-twice condition, replicating the testing effect. However, performance was similar across the quizzed conditions, indicating that testing promoted long-term retention regardless of test format (open-book versus closed-book) and test type (cued recall versus recognition). Open-book tests are not inferior to closed-book tests in building knowledge and can be particularly useful in online classes because preventing cheating is difficult when closed-book tests are administered online.

A lithiated m-terphenyl ligand bearing fluorine atoms at the ortho positions of the flanking aryl rings was synthesized and characterized using single crystal X-ray diffraction, variable-temperature multinuclear NMR spectroscopy, and computational methods. Changes in 1JC,F on coordination to lithium as a spectroscopic observable parametrizing the strength of the C-F···Li interaction are described, and a general, qualitative relationship between C-F bond lengths, Δ1JC,F values, and the extent of C-F bond activation as a result of Lewis acid coordination is proposed.

Chemical oxidation with hydroxyl radical (HO•) and sulfate radical (SO4•-) is often used to treat water contaminated with aromatic compounds. Although oxidation of aromatics by these radicals has been studied for decades, the commonly accepted transformation pathway-sequential hydroxylation of the ring followed by ring cleavage and mineralization of the resulting products-does not account for the loss of the parent compound observed during the initial phase of the process. To assess the importance of pathways for aromatic compound oxidation that do not result in ring hydroxylation, we identified products formed after the initial reaction between HO• or SO4•- and benzene, toluene, ethylbenzene, and (BTEX) xylene isomers. We quantified products of ring hydroxylation and oxidation of alkyl substituents as well as a suite of ring-cleavage products, including acetaldehyde, formic acid, 6-, 7-, or 8-carbon oxoenals and oxodials. Other ring-cleavage products, which were most likely aldehydes and organic acids, were observed but not quantified. When SO4•- was used as the oxidant, aromatic organosulfates also were formed. Our results indicated that the initial phase of the oxidation process involves radical addition, hydrogen abstraction, or one-electron transfer to the ring followed by reaction with O2. The hydroxycyclohexadienylperoxy radical produced in this reaction can eliminate hydroperoxyl radical (HO2•) to produce a phenolic compound or it can rearrange to form a bicyclic peroxy intermediate that subsequently undergoes ring cleavage. Hydroxylation of the ring and oxidation of the alkyl substituent accounted for approximately 15-40% of the reacted mass of the parent compound. Ring-cleavage products for which quantification was possible accounted for approximately 2 to 10% of the reacted mass. Our results raise concerns about the formation of toxic ring-cleavage products during the initial stage of oxidation whenever HO• or SO4•- is used for the treatment of water containing benzene or alkylbenzenes.

Reliable estimates of adult survival for many shorebird species are lacking. We used Cormack–Jolly–Seber (CJS) methods to provide an estimate of apparent, or local, survival (φ) of a population of whimbrels, Numenius phaeopus, breeding in the subarctic Churchill, Manitoba region. We used data collected in two time‐periods: 1973–1976 and 2010–2014. We also quantified nest‐site fidelity in 2010–2014 to provide context to our apparent survival estimates because mark‐recapture analyses cannot distinguish between mortality and permanent emigration. The most parsimonious CJS model did not include effects of sex or time on apparent adult survival in either period (φ = 0.76 ± 0.13 SE; φ = 0.75 ± 0.04 SE, 1973–1976 and 2010–2014, respectively). Additionally, observations of marked whimbrels between 2010 and 2019 (n = 124) showed that 61 of the 105 marked individuals (58.1%) were resighted. These estimates of return rates are, as expected, much lower than estimates of apparent survival. The median year‐to‐year distance between nests (n = 139) in 2010 to 2014 was 198 m ± 88 SE and did not differ significantly (p = 0.84) between females (x̄ = 721.9 m ± 119.8 SE) and males (x̄ = 720.3 m ± 83.1 SE). If our apparent survival estimate is indicative of true survivorship, then adult mortality during the non‐breeding season has remained constant over the last five decades, implying that the recent decline in whimbrel populations may stem largely from reduced fecundity, including egg or juvenile survival, rather than primarily from reduced adult survival.

Anaplastic large cell lymphoma (ALCL) is a rare form of non-Hodgkin lymphoma (NHL) that can be aggressive with rapid speed, thus mandating a timely diagnosis to optimize treatment and deter progression. NHL classically presents with lymphadenopathy and constitutional symptoms. However, ALCL can present with nonspecific cutaneous manifestations with minimal or absent constitutional symptoms. The cutaneous involvement may resemble common dermatologic conditions, delaying diagnosis. We present a case of an aggressive cutaneous ALCL lesion mimicking facial cellulitis that rapidly progressed from a small comedone to a large, exophytic mass over the course of 1 month. Prior to presentation at our institution, the patient was previously diagnosed and treated for suspected bacterial infection with no response to therapy. Core needle biopsy of the forehead lesion confirmed the diagnosis of anaplastic lymphoma kinase-negative ALCL. Chemotherapy with brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone was planned for a total of 6–8 cycles with curative intent. By cycle 5, positron emission tomography and computed tomography demonstrated response to therapy with no enlarged or metabolically active lymph nodes appreciated. Our case report highlights the importance of developing a broad differential diagnosis for ulcerative facial masses, particularly when unresponsive to antimicrobial therapies. Lymphomas should be included in the differential diagnosis of patients with rapidly growing facial lesions.

This study aimed to validate a novel parent-report measure of ADHD symptom inflation, the Parent-Reported ADHD Symptom Infrequency Scale (PRASIS), in a clinical sample. The PRASIS is composed of an Infrequency subscale and an ADHD subscale. Online participants were assigned to one of three groups: mothers of children with diagnosed ADHD (n = 110), mothers of children with diagnosed ODD and/or anxiety (n = 116), and mothers of children without ADHD, ODD, or anxiety. The third group was then randomized to either receive instructions to complete the questionnaire honestly (controls, n = 164) or to complete the questionnaire as if they were trying to convince a provider that their child has ADHD (simulators, n = 141). Results indicated good to excellent internal consistency (INF α = .83, ADHD Total α = .93); strong convergent validity of the PRASIS ADHD scale with the ADHD Rating Scale-5 (r(529) = .85, p < .001); excellent group discrimination of the PRASIS Infrequency scale and the PRASIS ADHD scale (η2 = 0.38–0.42); and specificity of 86.7, sensitivity of 67.4%, and an AUC of .86 for the Infrequency scale. Overall, these outcomes supported the utility of the PRASIS in samples including mothers of children with psychiatric diagnoses of ODD and/or anxiety. [ABSTRACT FROM AUTHOR]