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The Honduran education system was caught off guard when COVID-19 struck the country. With effectively no training or preparation and very few resources, educators across the country began providing distance learning classes in mid-March 2020. Overnight, educators faced significant obstacles in their quest to keep young people studying--teaching classes to students they could not see and engaging young people who lacked technology. Teachers and students began to experience social-emotional problems. This field note describes how the United States Agency for International Development's Asegurando la Educación project transitioned in-person social and emotional learning (SEL) activities in 135 schools to provide virtual SEL support to hundreds of thousands of beneficiaries across the county. We outline the SEL interventions that contributed to the lowest national dropout rate in five years, and enrollment rates in Asegurando's 135 schools some 5 percent higher than the national average. Finally, we believe this field note will contribute to the evidence base for how SEL can improve mental health and school retention during future crises.

Section headClinical/translational cancer immunotherapy.BackgroundThe goal of this study was to estimate the objective response rate for utomilumab in adults with immune checkpoint inhibitor (ICI)-refractory melanoma and non-small-cell lung cancer (NSCLC).MethodsUtomilumab was dosed intravenously every 4 weeks (Q4W) and adverse events (AEs) monitored. Tumor responses by RECIST1.1 were assessed by baseline and on-treatment scans. Tumor biopsies were collected for detection of programmed cell death ligand 1, CD8, 4-1BB, perforin, and granzyme B, and gene expression analyzed by next-generation sequencing. CD8+ T cells from healthy donors were stimulated with anti-CD3 ± utomilumab and compared with control.ResultsPatients with melanoma (n=43) and NSCLC (n=20) received utomilumab 0.24 mg/kg (n=36), 1.2 mg/kg (n=26), or 10 mg/kg (n=1). Treatment-emergent AEs (TEAEs) occurred in 55 (87.3%) patients and serious TEAEs in 18 (28.6%). Five (7.9%) patients discontinued owing to TEAEs. Thirty-two (50.8%) patients experienced treatment-related AEs, mostly grade 1-2. Objective response rate: 2.3% in patients with melanoma; no confirmed responses for patients with NSCLC. Ten patients each with melanoma (23.3%) or NSCLC (50%) had stable disease; respective median (95% confidence interval, CI) progression-free survival was 1.8 (1.7-1.9) and 3.6 (1.6-6.5) months. Utomilumab exposure increased with dose. The incidences of antidrug and neutralizing antibodies were 46.3% and 19.4%, respectively. Efficacy was associated with immune-active tumor microenvironments, and pharmacodynamic activity appeared to be blunted at higher doses.ConclusionsUtomilumab was well tolerated, but antitumor activity was low in patients who previously progressed on ICIs. The potential of 4-1BB agonists requires additional study to optimize efficacy while maintaining the tolerable safety profile.

The primary driver of nest failure for terrestrial birds is depredation, especially for ground-nesting species that arc vulnerable to a diverse guild of predators. However, descriptions of how complex predator-prey interactions happen, and ultimately lead to nest failures, are scarce. Herein, we provide observations collected from cameras stationed at nest sites as part of a larger study on Northern Bobwhite (Colinus virginianus) and Scaled Quail (Callipepla squamata) nesting behavior in the Oklahoma Panhandle during 2016. We observed 2 multi-episode (i.e.. multiple predator visits) diurnal nest depredation events at a nest of each species. In both instances, repeated nest depredation by hispid cotton rats (Sigmodon kispidus) as well as 2 different snake species resulted in nest abandonment. We observed that cotton rats routinely visited nest sites (up to 11 times in 1 diurnal period), and often entered the nest during oft' bouts (64% of off bouts) of the incubating females. By detailing interspecific interactions involved in nest depredation. we provide a glimpse into the complexity of the nesting ecology of ground-dwelling birds. These observations further reinforce the potential pitfalls of categorizing nest depredation events without camera data. Received 17 March 2022. Accepted 17 September 2022. Key words: camera, ground-nesting, nest predators. Northern Bobwhite. Scaled Quail. El factor principal de fracaso de la anidacion en aves terrestres es la depredacion. especialmcnte en especies que anidan en el suelo y son vulnerables a un gremio divcrso de depredadores. Sin embargo, las descripciones de como ocurren las interaeciones complejas depredador-presa. que llevan en ultima instancia al fracaso dc la anidacion. son escasas. Aqui proporcionamos obscrvacioncs realizadas con camaras trampa ubicadas en sitios tic anidacion conio parte de un estudio mas grande sobre comportamiento de anidacion dc las codornices Colinus virginiaitus y Callipepla squamata en Oklahoma Panhandle durante el 2016. Observamos 2 eventos de depredacion dinrna dc nido de episodios multiples (es deeir visitas de multiples depredadores) en un nido de cada especie. En ambos casos, la depredacion repetida del nido por ratas Sigmodon hispidus asi como de 2 especics diferentes de scrpientcs resulto en cl abandono del nido. Observamos que las ratas visitaron rutinariamente los sitios de anidacion (hasta 11 veces en un periodo diurno) y entraron al nido durante las salidas (64% de las salidas) dc las hembras que tncuban. Al detallar interaccioncs intcrcspccificas involucradas en depredacion dc nidos, damos un vistazo a la complcjidad dc la ecoiogia de anidacion de las aves tcrrestres. Estas obscrvacioncs retucr/.an mas los posibles obstaeulos de categorizar los eventos de depredacion dc nido sin usar camaras trampa. Palabras clave: aves terrcstrcs, camara. codornices. depredadores dc nido., The primary driver of nest failure for terrestrial birds is depredation (Ricklefs 1969, Martin 1992), especially for ground-nesting species that are vulnerable to a diverse guild of predator species (i.e., [...]

The seismic performance of Balboa Boulevard during the 1994 MW 6.7 Northridge earthquake was examined through nonlinear deformation analyses (NDAs) using advanced tools to (1) investigate the failure mechanism leading to ground deformations at this site; (2) evaluate the accuracy of the adopted analysis methods, engineering procedures, and state-of-the-art tools to reasonably estimate horizontal ground displacements; and (3) identify key factors and parameters contributing to earthquake-induced ground deformations at this site. One-dimensional (1D) liquefaction vulnerability indexes (LVIs) and permanent displacements using Newmark sliding block analyses were also estimated and compared against ground deformations observed after the earthquake. The geotechnical characterization of Balboa Boulevard was assessed based on field and laboratory data obtained from two investigation campaigns. Transitional probability geostatistics were used to develop stratigraphic models that capture the heterogeneity and the spatial variability patterns of sand-like and clay-like soils present at this site. The stratigraphic models were implemented in the finite difference software FLAC and the behavior of sand-like and clay-like soils simulated using the PM4Sand and PM4Silt constitutive models, respectively. Sensitivity analyses were performed to address uncertainties associated with the spatial variability of soils, input ground motions, the proportion of sand-like and clay-like soils within the soil deposit, and the strength properties of these materials. Results from NDAs suggest that a compounded effect of both liquefaction of sand-like soils and cyclic softening of clay-like soils led to the excessive ground deformations at Balboa Boulevard. This study sheds light on the importance of using appropriate engineering procedures and numerical modeling protocols in the prediction of deformation patterns, the selection of key input parameters, as well as the applicability of LVIs in complex sites.

ABSTRACT The 2019 Ridgecrest earthquake sequence produced a 4 July M 6.5 foreshock and a 5 July M 7.1 mainshock, along with 23 events with magnitudes greater than 4.5 in the 24 hr period following the mainshock. The epicenters of the two principal events were located in the Indian Wells Valley, northwest of Searles Valley near the towns of Ridgecrest, Trona, and Argus. We describe observed liquefaction manifestations including sand boils, fissures, and lateral spreading features, as well as proximate non-ground failure zones that resulted from the sequence. Expanding upon results initially presented in a report of the Geotechnical Extreme Events Reconnaissance Association, we synthesize results of field mapping, aerial imagery, and inferences of ground deformations from Synthetic Aperture Radar-based damage proxy maps (DPMs). We document incidents of liquefaction, settlement, and lateral spreading in the Naval Air Weapons Station China Lake US military base and compare locations of these observations to pre- and postevent mapping of liquefaction hazards. We describe liquefaction and ground-failure features in Trona and Argus, which produced lateral deformations and impacts on several single-story masonry and wood frame buildings. Detailed maps showing zones with and without ground failure are provided for these towns, along with mapped ground deformations along transects. Finally, we describe incidents of massive liquefaction with related ground failures and proximate areas of similar geologic origin without ground failure in the Searles Lakebed. Observations in this region are consistent with surface change predicted by the DPM. In the same region, geospatial liquefaction hazard maps are effective at identifying broad percentages of land with liquefaction-related damage. We anticipate that data presented in this article will be useful for future liquefaction susceptibility, triggering, and consequence studies being undertaken as part of the Next Generation Liquefaction project.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

BACKGROUND:Expressed on activated T and natural killer cells, 4-1BB/CD137 is a costimulatory receptor that signals a series of events resulting in cytokine secretion and enhanced effector function. Targeting 4-1BB/CD137 with agonist antibodies has been associated with tumor reduction and antitumor immunity. C-C chemokine receptor 4 (CCR4) is highly expressed in various solid tumor indications and associated with poor prognosis. This phase Ib, open-label study in patients with advanced solid tumors assessed the safety, efficacy, pharmacokinetics, and pharmacodynamics of utomilumab (PF-05082566), a human monoclonal antibody (mAb) agonist of the T-cell costimulatory receptor 4-1BB/CD137, in combination with mogamulizumab, a humanized mAb targeting CCR4 reported to deplete subsets of regulatory T cells (Tregs). METHODS:Utomilumab 1.2-5 mg/kg or 100 mg flat dose every 4 weeks plus mogamulizumab 1 mg/kg (weekly in Cycle 1 followed by biweekly in Cycles ≥2) was administered intravenously to 24 adults with solid tumors. Blood was collected pre- and post-dose for assessment of drug pharmacokinetics, immunogenicity, and pharmacodynamic markers. Baseline tumor biopsies from a subset of patients were also analyzed for the presence of programmed cell death-ligand 1 (PD-L1), CD8, FoxP3, and 4-1BB/CD137. Radiologic tumor assessments were conducted at baseline and on treatment every 8 weeks. RESULTS:No dose-limiting toxicities occurred and the maximum tolerated dose was determined to be at least 2.4 mg/kg per the time-to-event continual reassessment method. No serious adverse events related to either treatment were observed; anemia was the only grade 3 non-serious adverse event related to both treatments. Utomilumab systemic exposure appeared to increase with dose. One patient with PD-L1-refractory squamous lung cancer achieved a best overall response of partial response and 9 patients had a best overall response of stable disease. No patients achieved complete response. Objective response rate was 4.2% (95% confidence interval: 0.1-21.1%) per RECIST 1.1. Depletion of Tregs in peripheral blood was accompanied by evidence of T-cell expansion as assessed by T-cell receptor sequence analysis. CONCLUSIONS:The combination of utomilumab/mogamulizumab was safe and tolerable, and may be suitable for evaluation in settings where CCR4-expressing Tregs are suppressing anticancer immunity. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT02444793.

By 1985, approximately 400,000 ha of the keystone species Shinnery oak's (Quercus havardii) historic distribution had been eliminated for agricultural purposes across the southwestern United States. These trends indicate a need for targeted conservation and restoration efforts, especially considering the increased attention received for its role in providing habitat for endangered fauna. Setting spatially explicit conservation targets can be challenging for species with limited distributions, as the change in climate conditions over time may disconnect the relationship between environmental suitability and static, topo‐edaphic factors. Our objective was to identify areas for Shinnery oak restoration and conservation and explore the role climate plays in determining these areas while considering topo‐edaphic relationships. We constructed ecological niche models to estimate Shinnery oak's distribution under current climate conditions and temporally transferred our model using an ensemble‐mean of general circulation models to identify areas predicted to retain environmental suitability for Shinnery oak through 2100. The current distribution model was best informed by one climate and two topo‐edaphic variables. We created a second distribution model excluding topo‐edaphic variables to estimate future plant–climate relationships. Incorporating insights from models informed by both static (e.g. soil) and dynamic (e.g. climate) variables, we identified areas for conservation characterized by persistent climate suitability and high soil type suitability. Lastly, we incorporated data on land use and ownership to explore socio‐ecological influences on management decisions. By identifying areas of agreement between our modeled distributions and considering social context, we prioritized conservation areas where environmental suitability persists under changing conditions to facilitate restoration success. [ABSTRACT FROM AUTHOR]

Background: Sasanlimab (PF-06801591), a humanized immunoglobulin G4 monoclonal antibody, binds to programmed cell death protein-1 (PD-1), preventing ligand (PD-L1) interaction. Objectives: To evaluate pharmacokinetics (PK), safety, tolerability, and efficacy of two subcutaneous sasanlimab dosing regimens. Design: An open-label study consisting of phases Ib and II. Phase Ib: non-randomized, dose escalation, and expansion study in Asian participants with advanced malignancies. Phase II: conducted globally in participants with non-small-cell lung cancer with PD-L1 positive or PD-L1 status unknown tumors; participants were randomized 1:2 to receive subcutaneous sasanlimab 300 mg once every 4 weeks (300 mg-Q4W) or 600 mg once every 6 weeks (600 mg-Q6W). Methods: Primary endpoint in phase Ib: dose-limiting toxicity (DLT) occurring in first treatment cycle; in phase II: C trough and AUC. Results: A total of 155 participants (phase Ib, n = 34; phase II, n = 121) received sasanlimab. Phase Ib: no DLT reported. Phase II: ratio of adjusted geometric mean for AUCtau was 231.2 (90% CI, 190.1–281.2) and C trough was 111.5 (90% CI, 86.3–144.0) following 600 mg-Q6W (test) versus 300 mg-Q4W (reference). Phase Ib: grade 3 treatment-related adverse events (TRAEs) occurred in 1/4 (25%) and 3/12 (25%) participants treated in 300 mg-Q4W dose escalation and expansion cohorts, respectively. Phase II: grade 3 TRAEs occurred in 3/41 (7.3%) and 3/80 (3.8%) participants treated with 300 mg-Q4W and 600 mg-Q6W, respectively; no grade 4/5 TRAEs. Phase II: confirmed objective response was observed in 11/41 (26.8% (95% CI, 14.2–42.9)) and 12/80 (15.0% (95% CI, 8.0–24.7)) participants treated with 300 mg-Q4W and 600 mg-Q6W, respectively. Conclusions: Phase Ib regimens were considered safe with no DLTs reported. In phase II, 600 mg-Q6W regimen criteria were met for AUCtau and C trough metrics to support PK-based extrapolation of efficacy of alternative regimen. Regimens were well tolerated, showing anti-tumor activity in participants with advanced solid tumors. Administration of sasanlimab at a dose of 600 mg-Q6W subcutaneously may serve as a convenient alternative to 300 mg-Q4W administration. Trial registration: NCT04181788 (ClinicalTrials.gov); 2019-003818-14 (EudraCT). [ABSTRACT FROM AUTHOR]

Since recognizing the importance of bioavailability for understanding the toxicity of chemicals in sediments, mechanistic modeling has advanced over the last 40 years by building better tools for estimating exposure and making predictions of probable adverse effects. Our review provides an up‐to‐date survey of the status of mechanistic modeling in contaminated sediment toxicity assessments. Relative to exposure, advances have been most substantial for non‐ionic organic contaminants (NOCs) and divalent cationic metals, with several equilibrium partitioning‐based (Eq‐P) models having been developed. This has included the use of Abraham equations to estimate partition coefficients for environmental media. As a result of the complexity of their partitioning behavior, progress has been less substantial for ionic/polar organic contaminants. When the EqP‐based estimates of exposure and bioavailability are combined with water‐only effects measurements, predictions of sediment toxicity can be successfully made for NOCs and selected metals. Both species sensitivity distributions and toxicokinetic and toxicodynamic models are increasingly being applied to better predict contaminated sediment toxicity. Furthermore, for some classes of contaminants, such as polycyclic aromatic hydrocarbons, adverse effects can be modeled as mixtures, making the models useful in real‐world applications, where contaminants seldomly occur individually. Despite the impressive advances in the development and application of mechanistic models to predict sediment toxicity, several critical research needs remain to be addressed. These needs and others represent the next frontier in the continuing development and application of mechanistic models for informing environmental scientists, managers, and decisions makers of the risks associated with contaminated sediments. Environ Toxicol Chem 2024;43:1778–1794. © 2023 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. [ABSTRACT FROM AUTHOR]