Greenland's bed topography is a primary control on ice flow, grounding line migration, calving dynamics, and subglacial drainage. Moreover, fjord bathymetry regulates the penetration of warm Atlantic ...water (AW) that rapidly melts and undercuts Greenland's marine‐terminating glaciers. Here we present a new compilation of Greenland bed topography that assimilates seafloor bathymetry and ice thickness data through a mass conservation approach. A new 150 m horizontal resolution bed topography/bathymetric map of Greenland is constructed with seamless transitions at the ice/ocean interface, yielding major improvements over previous data sets, particularly in the marine‐terminating sectors of northwest and southeast Greenland. Our map reveals that the total sea level potential of the Greenland ice sheet is 7.42 ± 0.05 m, which is 7 cm greater than previous estimates. Furthermore, it explains recent calving front response of numerous outlet glaciers and reveals new pathways by which AW can access glaciers with marine‐based basins, thereby highlighting sectors of Greenland that are most vulnerable to future oceanic forcing.
Key Points
We present a comprehensive, seamless bed topography across the ice‐ocean margin around Greenland
Two to 4 times more glaciers have calving fronts grounded below 200 m compared to previous mappings
Total ice volume of Greenland is 2.99 ± 0.02 times 106 km3, yielding a potential sea level rise of 7.42 m, 7 cm greater than previous estimates
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Trophoblast cell-surface antigen-2 (Trop-2) is expressed in epithelial cancers, including hormone receptor-positive (HR+) metastatic breast cancer (mBC). Sacituzumab govitecan (SG; Trodelvy®) is an ...antibody–drug conjugate composed of a humanized anti-Trop-2 monoclonal antibody coupled to SN-38 at a high drug-to-antibody ratio via a unique hydrolyzable linker that delivers SN-38 intracellularly and in the tumor microenvironment. SG was granted accelerated FDA approval for metastatic triple-negative BC treatment in April 2020.
We analyzed a prespecified subpopulation of patients with HR+/human epidermal growth factor receptor 2-negative (HER2−) HR+/HER2− mBC from the phase I/II, single-arm trial (NCT01631552), who received intravenous SG (10 mg/kg) and whose disease progressed on endocrine-based therapy and at least one prior chemotherapy for mBC. End points included objective response rate (ORR; RECIST version 1.1) assessed locally, duration of response (DOR), clinical benefit rate, progression-free survival (PFS), overall survival (OS), and safety.
Fifty-four women were enrolled between 13 February 2015 and 1 June 2017. Median (range) age was 54 (33-79) years and all received at least two prior lines of therapy for mBC. At data cut-off (1 March 2019), 12 patients were still alive. Key grade ≥3 treatment-related toxicities included neutropenia (50.0%), anemia (11.1%), and diarrhea (7.4%). Two patients discontinued treatment due to treatment-related adverse events. No treatment-related deaths occurred. At a median follow-up of 11.5 months, the ORR was 31.5% 95% confidence interval (CI), 19.5%–45.6%; 17 partial responses; median DOR was 8.7 months (95% CI 3.7–12.7), median PFS was 5.5 months (95% CI 3.6–7.6), and median OS was 12 months (95% CI 9.0–18.2).
SG shows encouraging activity in patients with pretreated HR+/HER2− mBC and a predictable, manageable safety profile. Further evaluation in a randomized phase III trial (TROPiCS-02) is ongoing (NCT03901339).
ClinicalTrials.gov NCT01631552; https://clinicaltrials.gov/ct2/show/NCT01631552
•Safety and efficacy of sacituzumab govitecan (SG), a Trop-2–directed antibody–drug conjugate, were evaluated in patients with hormone receptor-positive/epidermal growth factor receptor 2-negative metastatic breast cancer (mBC).•Key grade ≥3 treatment-related toxicities included neutropenia (50.0%), anemia (11.1%), and diarrhea (7.4%).•In 54 patients who received SG (10 mg/kg) and at least two prior lines of therapy for mBC, the objective response rate was 31.5%.•Responses achieved with SG were durable, with a median duration of response of 8.7 months and a median progression-free survival of 5.5 months.•Clinical activity seen is encouraging in relation to current standard-of-care chemotherapies in this setting.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Anemia is common among people living with HIV infection (PLWH) and is associated with adverse health outcomes. Information on risk factors for anemia incidence in the current antiretroviral therapy ...(ART) era is lacking.
Within a prospective clinical cohort of adult PLWH receiving care at eight sites across the United States between 1/2010-3/2018, Cox proportional hazards regression analyses were conducted among a) PLWH free of anemia at baseline and b) PLWH free of severe anemia at baseline to determine associations between time-updated patient characteristics and development of anemia (hemoglobin < 10 g/dL), or severe anemia (hemoglobin < 7.5 g/dL). Linear mixed effects models were used to examine relationships between patient characteristics and hemoglobin levels during follow-up. Hemoglobin levels were ascertained using laboratory data from routine clinical care. Potential risk factors included: age, sex, race/ethnicity, body mass index, smoking status, hazardous alcohol use, illicit drug use, hepatitis C virus (HCV) coinfection, estimated glomerular filtration rate (eGFR), CD4 cell count, viral load, ART use and time in care at CNICS site.
This retrospective cohort study included 15,126 PLWH. During a median follow-up of 6.6 (interquartile range IQR 4.3-7.6) years, 1086 participants developed anemia and 465 participants developed severe anemia. Factors that were associated with incident anemia included: older age, female sex, black race, HCV coinfection, lower CD4 cell counts, VL ≥400 copies/ml and lower eGFR.
Because anemia is a treatable condition associated with increased morbidity and mortality among PLWH, hemoglobin levels should be monitored routinely, especially among PLWH who have one or more risk factors for anemia.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In the current work we present six hindcast WRF (Weather Research and Forecasting model) simulations for the EURO-CORDEX (European Coordinated Regional Climate Downscaling Experiment) domain with ...different configurations in microphysics, convection and radiation for the time period 1990–2008. All regional model simulations are forced by the ERA-Interim reanalysis and have the same spatial resolution (0.44°). These simulations are evaluated for surface temperature, precipitation, short- and longwave downward radiation at the surface and total cloud cover. The analysis of the WRF ensemble indicates systematic temperature and precipitation biases, which are linked to different physical mechanisms in the summer and winter seasons. Overestimation of total cloud cover and underestimation of downward shortwave radiation at the surface, mostly linked to the Grell–Devenyi convection and CAM (Community Atmosphere Model) radiation schemes, intensifies the negative bias in summer temperatures over northern Europe (max −2.5 °C). Conversely, a strong positive bias in downward shortwave radiation in summer over central (40–60%) and southern Europe mitigates the systematic cold bias over these regions, signifying a typical case of error compensation. Maximum winter cold biases are over northeastern Europe (−2.8 °C); this location suggests that land–atmosphere rather than cloud–radiation interactions are to blame. Precipitation is overestimated in summer by all model configurations, especially the higher quantiles which are associated with summertime deep cumulus convection. The largest precipitation biases are produced by the Kain–Fritsch convection scheme over the Mediterranean. Precipitation biases in winter are lower than those for summer in all model configurations (15–30%). The results of this study indicate the importance of evaluating not only the basic climatic parameters of interest for climate change applications (temperature and precipitation), but also other components of the energy and water cycle, in order to identify the sources of systematic biases, possible compensatory or masking mechanisms and suggest pathways for model improvement.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
We present the first direct carrier-envelope-offset (CEO) frequency detection of a modelocked laser based on supercontinuum generation (SCG) in a CMOS-compatible silicon nitride (Si(3)N(4)) ...waveguide. With a coherent supercontinuum spanning more than 1.5 octaves from visible to beyond telecommunication wavelengths, we achieve self-referencing of SESAM modelocked diode-pumped Yb:CALGO lasers using standard f-to-2f interferometry. We directly obtain without amplification strong CEO beat signals for both a 100-MHz and 1-GHz pulse repetition rate laser. High signal-to-noise ratios (SNR) of > 25 dB and even > 30 dB have been generated with only 30 pJ and 36 pJ of coupled pulse energy from the megahertz and gigahertz laser respectively. We compare these results to self-referencing using a commercial photonic crystal fiber and find that the required peak power for CEO beat detection with a comparable SNR is lowered by more than an order of magnitude when using a Si(3)N(4) waveguide.
Brain development has largely been studied through unimodal analysis of neuroimaging data, providing independent results for structural and functional data. However, structure clearly impacts ...function and vice versa, pointing to the need for performing multimodal data collection and analysis to improve our understanding of brain development, and to further inform models of typical and atypical brain development across the lifespan. Ultimately, such models should also incorporate genetic and epigenetic mechanisms underlying brain structure and function, although currently this area is poorly specified. To this end, we are reporting here a multi-site, multi-modal dataset that captures cognitive function, brain structure and function, and genetic and epigenetic measures to better quantify the factors that influence brain development in children originally aged 9–14 years. Data collection for the Developmental Chronnecto-Genomics (Dev-CoG) study (http://devcog.mrn.org/) includes cognitive, emotional, and social performance scales, structural and functional MRI, diffusion MRI, magnetoencephalography (MEG), and saliva collection for DNA analysis of single nucleotide polymorphisms (SNPs) and DNA methylation patterns. Across two sites (The Mind Research Network and the University of Nebraska Medical Center), data from over 200 participants were collected and these children were re-tested annually for at least 3 years. The data collection protocol, sample demographics, and data quality measures for the dataset are presented here. The sample will be made freely available through the collaborative informatics and neuroimaging suite (COINS) database at the conclusion of the study.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Wild birds carry a number of infectious agents, some of which may have pathogenic potential for the host and others species, including humans. Domestic pigeons (Columba livia) are important targets ...of study since these increasingly cohabit urban spaces, being possible spillover sources of pathogens to humans. In the present study, two genomes (PiGyV_Tq/RS/Br and PiGyV_RG/RS/Br), representative of Gyrovirus genus, family Anelloviridae, were detected in sera of free-living pigeons collected in Southern Brazil. The genomes exhibit less than 50% identity to previously described members of Gyrovirus genus, suggesting that they constitute a new viral species circulating in pigeons, to which the name “pigeon gyrovirus (PiGyV)” is proposed. The current study characterizes these two PiGyV genomes which, to date, are the first gyrovirus species identified in domestic pigeons.
•Pigeons may be carriers of virus with potential impact for public or animal health.•Two genomes of a novel Gyrovirus species are characterized in pigeons.•This is the first evidence of Gyrovirus circulation in pigeons.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Social support (SS) predicts health outcomes among patients living with HIV. We administered a brief, validated measure of SS, the Multifactoral Assessment of Perceived Social Support, within a ...patient-reported outcomes assessment of health domains in HIV care at 4 U.S. clinics in English and Spanish (n = 708). In univariate analysis, low SS was associated with poorer engagement in care, antiretroviral adherence, and health-related quality of life; current methamphetamine/crystal use, depression, anxiety, and HIV stigma (all p < 0.001); any use of either methamphetamines/crystal, illicit opioids, or cocaine/crack (p = 0.001), current marijuana use (p = 0.012), nicotine use (p = 0.005), and concern for sexually transmitted infection exposure (p = 0.001). High SS was associated with undetectable viral load (p = 0.031). Multivariate analyses found low SS independently associated with depression (risk ratio (RR) 3.72, 95% CI 2.93-4.72), lower adherence (RR 0.76, 95% CI 0.64-0.89), poor engagement in care (RR 2.05, 95% CI 1.44-2.96), and having more symptoms (RR 2.29, 95% CI 1.92-2.75). Medium SS was independently associated with depression (RR 2.59, 95% CI 2.00-3.36), poor engagement in care (RR 1.62, 95% CI 1.15-2.29) and having more symptoms (RR 1.75, 95% CI 1.44-2.13). SS assessment may help identify patients at risk for these outcomes.
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DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Therapy-related acute promyelocytic leukemia (t-APL) is relatively rare, with limited data on outcome after treatment with arsenic trioxide (ATO) compared to standard intensive chemotherapy (CTX). We ...evaluated 103 adult t-APL patients undergoing treatment with all-trans retinoic acid (ATRA) alone (n=7) or in combination with ATO (n=24), CTX (n=53), or both (n=19). Complete remissions were achieved after induction therapy in 57% with ATRA, 100% with ATO/ATRA, 78% with CTX/ATRA, and 95% with CTX/ATO/ATRA. Early death rates were 43% for ATRA, 0% for ATO/ATRA, 12% for CTX/ATRA and 5% for CTX/ATO/ATRA. Three patients relapsed, two developed therapy-related acute myeloid leukemia and 13 died in remission including seven patients with recurrence of the prior malignancy. Median follow-up for survival was 3.7 years. None of the patients treated with ATRA alone survived beyond one year. Event-free survival was significantly higher after ATO-based therapy (95%, 95% CI, 82-99%) as compared to CTX/ATRA (78%, 95% CI, 64-87%; P=0.042), if deaths due to recurrence of the prior malignancy were censored. The estimated 2-year overall survival in intensively treated patients was 88% (95% CI, 80-93%) without difference according to treatment (P=0.47). ATO when added to ATRA or CTX/ATRA is feasible and leads to better outcomes as compared to CTX/ATRA in t-APL.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Among people living with HIV (PLWH), physical intimate partner violence (IPV) is associated with poor virologic, psychiatric, and behavioral outcomes. We examined non-physical, psychological intimate ...partner violence (psy-IPV) and HIV care outcomes using data from two U.S. consortia.
We conducted multivariable analyses with robust standard errors to compare patients indicating/not indicating psy-IPV.
Among PLWH (n = 5950), 9.5% indicated psy-IPV; these individuals were younger (- 3; 95% CI - 2,-4, p-value < 0.001), less likely to be on antiretroviral treatment (ART) (0.73 0.55,0.97, p = 0.03), less adherent to ART (- 4.2 - 5.9,-2.4, p < 0.001), had higher odds of detectable viral load (1.43 1.15,1.78, p = 0.001) and depression (2.63 2.18,3.18, p < 0.001), and greater use of methamphetamines/crystal 2.98 (2.30,3.87),p < 0.001, cocaine/crack 1.57 (1.24,1.99),p < 0.001, illicit opioids 1.56 (1.13,2.16),p = 0.007, and marijuana 1.40 (1.15,1.70), p < 0.001.
Psychological IPV, even in the absence of physical or sexual IPV, appears to be associated with HIV care outcomes and should be included in IPV measures integrated into routine HIV care.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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