Ocean circulation and variability beneath Nioghalvfjerdsbrae (79 North Glacier) ice tongue

Author Posting. © American Geophysical Union, 2020. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research: Oceans 125(8), (2020): e2020JC016091, doi:10.1029/2020JC016091.The floating ice tongue of 79 North Glacier, a major outlet glacier of the Northeast Greenland Ice Stream, has thinned by 30% since 1999. Earlier studies have indicated that long‐term warming of Atlantic Intermediate Water (AIW) is likely driving increased basal melt, causing the observed thinning. Still, limited ocean measurements in 79 North Fjord beneath the ice tongue have made it difficult to test this hypothesis. Here we use data from an Ice Tethered Mooring (ITM) deployed in a rift in the ice tongue from August 2016 to July 2017 to show that the subannual AIW temperature variability is smaller than the observed interannual variability, supporting the conclusion that AIW has warmed over the period of ice tongue thinning. In July 2017, the AIW at 500 m depth in the ice tongue cavity reached a maximum recorded temperature of 1.5°C. Velocity measurements reveal weak tides and a mean overturning circulation, which is likely seasonally enhanced by subglacial runoff discharged at the grounding line. Deep inflow of AIW and shallow export of melt‐modified water persist throughout the record, indicating year‐round basal melting of the ice tongue. Comparison with a mooring outside of the cavity suggests a rapid exchange between the cavity and continental shelf. Warming observed during 2016–2017 is estimated to drive a 33 ± 20% increase in basal melt rate near the ice tongue terminus and a 14 ± 2% increase near the grounding line if sustained.Funding for the ITM was provided by the Grossman Family Foundation through the WHOI Development Office. M. R. L. is supported by a National Defense Science and Engineering Graduate Fellowship. N. L. B. is supported by a grant from the National Science Foundation (NSF OCE‐1536856).2021-02-1

Durable Objective Response to Lurbinectedin in Small Cell Bladder Cancer with TP53 Mutation: A Molecular-Directed Strategy

Small cell bladder cancer (SCBC) is a rare and aggressive disease, often treated with platinum/etoposide-based chemotherapy. Key molecular drivers include the inactivation of onco-suppressor genes (TP53, RB1) and amplifications in proto-oncogenes (MYC). We report a patient with SCBC who achieved an objective and prolonged response to lurbinectedin, which has been approved for metastatic small cell lung cancer, after developing disease progression on cisplatin/etoposide and nivolumab/ipilimumab. A genomic analysis of a metastatic biopsy prior to lurbinectedin initiation revealed a TP53 mutation and amplification of the cell cycle regulators E2F3 and MYCL. A repeat biopsy following the development of lurbinectedin resistance showed a new actionable ERBB2 alteration without significant change in the tumor mutation burden (six mutations/Mb). The present report suggests that lurbinectedin may be active and should be further explored in SCBC harboring TP53 mutations and amplifications in E2F3 and MYC family complexes

Adaptive introgression facilitate adaptation to high latitudes in European aspen (Populus tremula L.)

Understanding local adaptation has become a key research area given the ongoing climate challenge and the concomitant requirement to conserve genetic resources. Perennial plants, such as forest trees, are good models to study local adaptation given their wide geographic distribution, largely outcrossing mating systems and demographic histories. We evaluated signatures of local adaptation in European aspen (Populus tremula) across Europe by means of whole genome re-sequencing of a collection of 411 individual trees. We dissected admixture patterns between aspen lineages and observed a strong genomic mosaicism in Scandinavian trees, evidencing different colonization trajectories into the peninsula from Russia, Central and Western Europe. As a consequence of the secondary contacts between populations after the last glacial maximum (LGM), we detected an adaptive introgression event in a genome region of ∼500kb in chromosome 10, harboring a large-effect locus that has previously been shown to contribute to adaptation to the short growing seasons characteristic of northern Scandinavia. Demographic simulations and ancestry inference suggest an Eastern origin - probably Russian - of the adaptive Nordic allele which nowadays is present in a homozygous state at the north of Scandinavia. The strength of introgression and positive selection signatures in this region is a unique feature in the genome. Furthermore, we detected signals of balancing selection, shared across regional populations, that highlight the importance of standing variation as a primary source of alleles that facilitate local adaptation. Our results therefore emphasize the importance of migration-selection balance underlying the genetic architecture of key adaptive quantitative traits

Stranger Things: New Roles and Opportunities for Androgen Receptor in Oncology Beyond Prostate Cancer

The androgen receptor (AR) is one of the oldest therapeutic targets in oncology and continues to dominate the treatment landscape for advanced prostate cancer, where nearly all treatment regimens include some form of AR modulation. In this regard, AR remains the central driver of prostate cancer cell biology. Emerging preclinical and clinical data implicate key roles for AR in additional cancer types, thereby expanding the importance of this drug target beyond prostate cancer. In this mini-review, new roles for AR in other cancer types are discussed as well as their potential for treatment with AR-targeted agents. Our understanding of these additional functions for AR in oncology expand this receptor\u27s potential as a therapeutic target and will help guide the development of new treatment approaches

Mid-Holocene, coral-based sea surface temperatures in the western tropical Atlantic

© The Author(s), 2019. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial‐NoDerivs License. The definitive version was published in Rodriguez, L. G., Cohen, A. L., Ramirez, W., Oppo, D. W., Pourmand, A., Edwards, R. L., Alpert, A. E., & Mollica, N. Mid-Holocene, coral-based sea surface temperatures in the western tropical Atlantic. Paleoceanography and Paleoclimatology, 34(7), (2019): 1234-1245, doi:10.1029/2019PA003571.The Holocene is considered a period of relative climatic stability, but significant proxy data‐model discrepancies exist that preclude consensus regarding the postglacial global temperature trajectory. In particular, a mid‐Holocene Climatic Optimum, ~9,000 to ~5,000 years BP, is evident in Northern Hemisphere marine sediment records, but its absence from model simulations raises key questions about the ability of the models to accurately simulate climate and seasonal biases that may be present in the proxy records. Here we present new mid‐Holocene sea surface temperature (SST) data from the western tropical Atlantic, where twentieth‐century temperature variability and amplitude of warming track the twentieth‐century global ocean. Using a new coral thermometer Sr‐U, we first developed a temporal Sr‐U SST calibration from three modern Atlantic corals and validated the calibration against Sr‐U time series from a fourth modern coral. Two fossil corals from the Enriquillo Valley, Dominican Republic, were screened for diagenesis, U‐series dated to 5,199 ± 26 and 6,427 ± 81 years BP, respectively, and analyzed for Sr/Ca and U/Ca, generating two annually resolved Sr‐U SST records, 27 and 17 years long, respectively. Average SSTs from both corals were significantly cooler than in early instrumental (1870–1920) and late instrumental (1965–2016) periods at this site, by ~0.5 and ~0.75 °C, respectively, a result inconsistent with the extended mid‐Holocene warm period inferred from sediment records. A more complete sampling of Atlantic Holocene corals can resolve this issue with confidence and address questions related to multidecadal and longer‐term variability in Holocene Atlantic climate.This study was supported by NSF OCE 1747746 to Anne Cohen and by NSF OCE 1805618 to Anne Cohen and Delia Oppo. Eric Loss and his crew on Pangaea Exploration's Sea Dragon enabled fieldwork in Martinique, and George P. Lohman, Thomas DeCarlo, and Hanny Rivera assisted with coral coring. Kathryn Pietro and Julia Middleton assisted in the laboratory, and Louis Kerr provided technical support on the SEM at MBL. Gretchen Swarr provided technical support on the Element and iCap ICPMS at WHOI. We also thank Edwin Hernandez, Jose Morales, and Amos Winter for discussion. All data generated in this study will be made publicly available at http://www.ncdc.noaa.gov/data‐ access/paleoclimatology‐data/dataset

Immunoassay Urine Drug Testing among Patients Receiving Opioids at a Safety-Net Palliative Medicine Clinic

BACKGROUND: Few studies have examined the use of immunoassay urine drug testing of cancer patients in palliative care clinics. OBJECTIVES: We examined the frequency of immunoassay urine drug test (UDT) abnormalities and the factors associated with aberrancy at a safety-net hospital palliative medicine clinic. METHODS: A retrospective review of the electronic medical records of consecutive eligible patients seen at the outpatient palliative medicine clinic in a resource-limited safety-net hospital system was conducted between 1 September 2015 and 31 December 2020. We collected longitudinal data on patient demographics, UDT findings, and potential predictors of aberrant results. RESULTS: Of the 913 patients in the study, 500 (55%) underwent UDT testing, with 455 (50%) having the testing within the first three visits. Among those tested within the first three visits, 125 (27%) had aberrant UDT results; 44 (35%) of these 125 patients were positive for cocaine. In a multivariable regression model analysis of predictors for aberrant UDT within the first three visits, non-Hispanic White race (odds ratio (OR) = 2.13; 95% confidence interval (CI): 1.03-4.38; CONCLUSION: Despite limitations of immunoassay UDT, it was able to detect aberrant drug-taking behaviors in a significant number of patients seen at a safety-net hospital palliative care clinic, including cocaine use. These findings support universal UDT monitoring and utility of immunoassay-based UDT in resource-limited settings

Adherence to Opioid Patient Prescriber Agreements at a Safety Net Hospital

Patient prescriber agreements, also known as opioid contracts or opioid treatment agreements, have been recommended as a strategy for mitigating non-medical opioid use (NMOU). The purpose of our study was to characterize the proportion of patients with PPAs, the rate of non-adherence, and clinical predictors for PPA completion and non-adherence. This retrospective study covered consecutive cancer patients seen at a palliative care clinic at a safety net hospital between 1 September 2015 and 31 December 2019. We included patients 18 years or older with cancer diagnoses who received opioids. We collected patient characteristics at consultation and information regarding PPA. The primary purpose was to determine the frequency and predictors of patients with a PPA and non-adherence to PPAs. Descriptive statistics and multivariable logistic regression models were used for the analysis. The survey covered 905 patients having a mean age of 55 (range 18-93), of whom 474 (52%) were female, 423 (47%) were Hispanic, 603 (67%) were single, and 814 (90%) had advanced cancer. Of patients surveyed, 484 (54%) had a PPA, and 50 (10%) of these did not adhere to their PPA. In multivariable analysis, PPAs were associated with younger age (odds ratio [OR] 1.44

Incidence and Risk Factors for Pneumonitis Associated With Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer: A Single Center Experience

INTRODUCTION: Immune checkpoint inhibitor (ICI) pneumonitis causes substantial morbidity and mortality. Estimates of real-world incidence and reported risk factors vary substantially. METHODS: We conducted a retrospective review of 419 patients with advanced non-small cell lung cancer (NSCLC) who were treated with anti-PD-(L)1 with or without anti-CTLA-4 therapy. Clinical, imaging, and microbiological data were evaluated by multidisciplinary adjudication teams. The primary outcome of interest was grade ≥2 (CTCAEv5) pneumonitis. Clinicopathologic variables, tobacco use, cancer therapies, and preexisting lung disease were assessed for univariate effects using Cox proportional hazards models. We created multivariate Cox proportional hazards models to assess risk factors for pneumonitis and mortality. Pneumonitis, pneumonia, and progression were modeled as time-dependent variables in mortality models. RESULTS: We evaluated 419 patients between 2013 and 2021. The cumulative incidence of pneumonitis was 9.5% (40/419). In a multivariate model, pneumonitis increased the risk for mortality (HR 1.6, 95% CI, 1.0-2.5), after adjustment for disease progression (HR 1.6, 95% CI, 1.4-1.8) and baseline shortness of breath (HR 1.5, 95% CI, 1.2-2.0). Incomplete resolution was more common with more severe pneumonitis. Interstitial lung disease was associated with higher risk for pneumonitis (HR 5.4, 95% CI, 1.1-26.6), particularly in never smokers (HR 26.9, 95% CI, 2.8-259.0). CONCLUSION: Pneumonitis occurred at a high rate and significantly increased mortality. Interstitial lung disease, particularly in never smokers, increased the risk for pneumonitis