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We evaluate tropical cyclones (TCs) in a set of thermodynamic global warming (TGW) simulations over the continental United States (CONUS). A 12 km simulation forced by ERA5 provides a 40-year historical (1980–2019) control. Four complimentary future scenarios are generated using thermodynamic deltas applied to lateral boundary, interior, and surface forcing. We curate a data set of 4,498 6-hourly TC snapshots in the control and find a corresponding “twin” in each counterfactual, permitting a paired comparison. Warming results in an increase in mean dynamical TC intensity and moisture-related quantities, with the latter being more pronounced. TC inner cores contract slightly but outer storm size remains unchanged. The frequency with which TCs become more intense is only moderately consistent, with snapshots having increased hazards ranging from 50% to 80% depending on warming level. The fractions of TCs undergoing rapid intensification and weakening both increase across all warming simulations, suggesting elevated short-term intensity variability.

PurposeTo assess the safety and efficacy of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor osimertinib as neoadjuvant therapy in patients with surgically resectable stage I-IIIA EGFR-mutated non-small cell lung cancer (NSCLC).Patients and methodsThis was a multi-institutional phase II trial of neoadjuvant osimertinib for patients with surgically resectable stage I-IIIA (American Joint Committee on Cancer [AJCC] V7) EGFR-mutated (L858R or exon 19 deletion) NSCLC (ClinicalTrials.gov identifier: NCT03433469). Patients received osimertinib 80 mg orally once daily for up to two 28-day cycles before surgical resection. The primary end point was major pathological response (MPR) rate. Secondary safety and efficacy end points were also assessed. Exploratory end points included pretreatment and post-treatment tumor mutation profiling.ResultsA total of 27 patients were enrolled and treated with neoadjuvant osimertinib for a median 56 days before surgical resection. Twenty-four (89%) patients underwent subsequent surgery; three (11%) patients were converted to definitive chemoradiotherapy. The MPR rate was 14.8% (95% CI, 4.2 to 33.7). No pathological complete responses were observed. The ORR was 52%, and the median DFS was 40.9 months. One treatment-related serious adverse event (AE) occurred (3.7%). No patients were unable to undergo surgical resection or had surgery delayed because of an AE. The most common co-occurring tumor genomic alterations were in TP53 (42%) and RBM10 (21%).ConclusionTreatment with neoadjuvant osimertinib in surgically resectable (stage IA-IIIA, AJCC V7) EGFR-mutated NSCLC did not meet its primary end point for MPR rate. However, neoadjuvant osimertinib did not lead to unanticipated AEs, surgical delays, nor result in a significant unresectability rate.

The California-Nevada 1997 New Year’s flood was an atmospheric river (AR)-driven rain-on-snow (RoS) event and remains the costliest in their history. The joint occurrence of saturated soils, rainfall, and snowmelt generated inundation throughout northern California-Nevada. Although AR RoS events are projected to occur more frequently with climate change, the warming sensitivity of their flood drivers across scales remains understudied. We leverage the regionally refined mesh capabilities of the Energy Exascale Earth System Model (RRM-E3SM) to recreate the 1997 New Year’s flood with horizontal grid spacings of 3.5 km across California, with forecast lead times of up to 4 days, and across six warming levels ranging from pre-industrial conditions to +3.5∘C. We describe the sensitivity of the flood drivers to warming including AR duration and intensity, precipitation phase, intensity and efficiency, snowpack mass and energy changes, and runoff efficiency. Our findings indicate current levels of climate change negligibly influence the flood drivers. At warming levels ≥1.7∘C, AR hazard potential increases, snowpack nonlinearly decreases, antecedent soil moisture decreases (except where the snowline retreats), and runoff decreases (except in the southern Sierra Nevada where antecedent snowpack persists). Storm total precipitation increases, but at rates below warming-induced increases in saturation-specific humidity. Warming intensifies short-duration, high-intensity rainfall, particularly where snowfall-to-rainfall transitions occur. This study highlights the nonlinear tradeoffs in 21st-century RoS flood hazards with warming and provides water management and infrastructure investment adaptation considerations.

Aging dogs serve as a valuable preclinical model for Alzheimer's disease (AD) due to their natural age-related development of β-amyloid (Aβ) plaques, human-like metabolism, and large brains that are ideal for studying structural brain aging trajectories from serial neuroimaging. Here we examined the effects of chronic treatment with the calcineurin inhibitor (CNI) tacrolimus or the nuclear factor of activated T cells (NFAT)-inhibiting compound Q134R on age-related canine brain atrophy from a longitudinal study in middle-aged beagles (36 females, 7 males) undergoing behavioral enrichment. Annual MRI was analyzed using modern, automated techniques for region-of-interest-based and voxel-based volumetric assessments. We found that the frontal lobe showed accelerated atrophy with age, while the caudate nucleus remained relatively stable. Remarkably, the hippocampus increased in volume in all dogs. None of these changes were influenced by tacrolimus or Q134R treatment. Our results suggest that behavioral enrichment can prevent atrophy and increase the volume of the hippocampus but does not prevent aging-associated prefrontal cortex atrophy.

Reciprocal interactions between alveolar fibroblasts and epithelial cells are crucial for lung homeostasis, injury repair, and fibrogenesis, but underlying mechanisms remain unclear. To investigate, we administered the fibroblast-selective TGF-β1 signaling inhibitor epigallocatechin gallate (EGCG) to interstitial lung disease (ILD) patients undergoing diagnostic lung biopsy and conducted single-cell RNA-Seq on spare tissue. Biopsies from untreated patients showed higher fibroblast TGF-β1 signaling compared with nondisease donor or end-stage ILD tissues. In vivo, EGCG downregulated TGF-β1 signaling and several proinflammatory and stress pathways in biopsy samples. Notably, EGCG reduced fibroblast secreted frizzled-related protein 2 (sFRP2), an unrecognized TGF-β1 fibroblast target gene induced near type II alveolar epithelial cells (AEC2s) in situ. Using AEC2-fibroblast coculture organoids and precision-cut lung slices (PCLSs) from nondiseased donors, we found TGF-β1 signaling promotes a spread AEC2 KRT17+ basaloid state, whereupon sFRP2 then activates a mature cytokeratin 5+ (Krt5+) basal cell program. Wnt-receptor Frizzled 5 (Fzd5) expression and downstream calcineurin signaling were required for sFRP2-induced nuclear NFATc3 accumulation and KRT5 expression. These findings highlight stage-specific TGF-β1 signaling in ILD and the therapeutic potential of EGCG in reducing idiopathic pulmonary fibrosis-related (IPF-related) transcriptional changes and identify TGF-β1/noncanonical Wnt pathway crosstalk via sFRP2 as a mechanism for dysfunctional epithelial signaling in IPF/ILD.

We examine whether one of the most popular observation systems in teacher evaluation--the Framework for Teaching (FFT)--captures the range of instructional skills teachers need to be effective. We focus on the case of special educators, who are likely to use instructional approaches that, although supported by research, are de-emphasized in common observation systems. Drawing on 206 lessons from 51 teachers, we compare FFT scores to an observation system from special education. We find that FFT's psychometric properties are consistent with previous studies, but the system is limited in assessing the quality of instructional practices used in special education. We discuss implications of these findings for two practical uses of observations--supporting teacher development and informing human capital decisions.

The 1997 New Year's flood event was the most costly in California's history. This compound extreme event was driven by a category 5 atmospheric river that led to widespread snowmelt. Extreme precipitation, snowmelt, and saturated soils produced heavy runoff causing widespread inundation in the Sacramento Valley. This study recreates the 1997 flood using the Regionally Refined Mesh capabilities of the Energy Exascale Earth System Model (RRM-E3SM) under prescribed ocean conditions. Understanding the processes causing extreme events informs practical efforts to anticipate and prepare for such events in the future, and also provides a rich context to evaluate model skill in representing extremes. Three California-focused RRM grids, with horizontal resolution refinement of 14 km down to 3.5 km, and six forecast lead times, 28 December 1996 at 00Z through 30 December 1996 at 12Z, are assessed for their ability to recreate the 1997 flood. Planetary to synoptic scale atmospheric circulations and integrated vapor transport are weakly influenced by horizontal resolution refinement over California. Topography and mesoscale circulations, such as the Sierra barrier jet, are better represented at finer horizontal resolutions resulting in better estimates of storm total precipitation and storm duration snowpack changes. Traditional time-series and causal analysis frameworks are used to examine runoff sensitivities state-wide and above major reservoirs. These frameworks show that horizontal resolution plays a more prominent role in shaping reservoir inflows, namely the magnitude and time-series shape, than forecast lead time, 2-to-4 days prior to the 1997 flood onset.

Developing actionable climate information and integrating it into decision-making are two crucial elements for promoting effective societal responses to climate change. However, what constitutes actionable climate information, and how it is used, varies based on the actors, systems, and scales that are relevant to specific decisions. Yet, the terms ‘actionable climate information’ or ‘use of climate information’ are used abstractly. There is a lack of holistic understanding of the various types of information that can be deemed as usable by different users, and the different ways in which they may be used in decision-making. Typologies or generalizable categorizations can help both knowledge producers and users to better envision the entire landscape of climate information and its uses and can help to reduce the time and cost of actionable knowledge production. Through systematic coding and analysis of ∼ 4 years of co-production engagements between climate scientists and resource managers, this paper presents empirically derived typologies of actionable climate information and its use, and explores whether certain uses are better informed by specific types of climate information. These typologies provide a valuable starting point for climate information producers, users, and boundary spanners working on climate-informed resource management, to reduce some of the time-intensive elements of the process.

Regional climate models can be used to examine how past weather events might unfold under different climate conditions by simulating analogue versions of those events with modified thermodynamic conditions (i.e., warming signals). Here, we apply this approach by dynamically downscaling a 40-year sequence of past weather from 1980-2019 driven by atmospheric re-analysis, and then repeating this 40-year sequence a total of 8 times using a range of time-evolving thermodynamic warming signals that follow 4 80-year future warming trajectories from 2020-2099. Warming signals follow two emission scenarios (SSP585 and SSP245) and are derived from two groups of global climate models based on whether they exhibit relatively high or low climate sensitivity. The resulting dataset, which contains 25 hourly and over 200 3-hourly variables at 12 km spatial resolution, can be used to examine a plausible range of future climate conditions in direct reference to previously observed weather and enables a systematic exploration of the ways in which thermodynamic change influences the characteristics of historical extreme events.

Student evaluations of teaching (SETs) are important at most colleges and universities. One purpose of this study was to determine the extent to which motivational climate was associated with SETs. Another purpose was to determine whether course ease was associated with SETs. Participants included 2,949 undergraduate students from 30 courses at a large public university. Using hierarchical linear modeling, we examined the extent to which students' motivation-related course perceptions (empowerment/autonomy, usefulness, success expectancies, situational interest, and caring) related to SETs at the student and class levels. SETs were highly associated with motivational climate. Furthermore, easier courses were rated lower by students when controlling for motivational climate and the demographical composition of the class. These findings highlight the association between the motivational climate and SETs and suggest that one way to improve SETs may be for instructors to focus on improving the motivational climate rather than making the course easier.

Several large-scale survey efforts have attempted to understand teachers' experiences in the early months of the pandemic. Our study complements this literature by providing direct evidence of teachers' work prior to and after the onset of COVID-19. We leverage unique longitudinal time use and affect data on 131 teachers from one district across the 2019-2020 school year. Specifically, we provide a full accounting of teachers' instructional activities, their reports of their positive affect and negative affect while engaged in these activities, and the extent to which teachers' work experiences changed post-COVID. Our results suggest a large reduction in teachers' daily instructional minutes, which were replaced with increased planning, paperwork, and interactions with colleagues and parents. Teachers' overall positive and negative affect did not change post-COVID. But teachers' affective responses to specific work activities did. Post-COVID, we saw increases in teachers' positive affect when with students.

A course syllabus can affect students' perceptions of the motivational climate within a course. Yet, few researchers have conducted experimental studies of students' perceptions of syllabi in courses in which they were currently enrolled. The purpose of the present studies was to assess the extent to which syllabi language and organization affected students' motivation-related perceptions in hypothetical and real courses. In Study 1, undergraduate students reported their motivation-related perceptions for hypothetical syllabi statements about the course overview, late submissions, attendance, and use of electronics. Statistically significant differences in perceptions were documented between different types of syllabi statements. Study 2 was an experimental study in which students in a "real" course were randomly assigned either a regular syllabus or one that was designed to increase their motivation-related perceptions. No statistically significant differences were documented between the two groups for students' motivation-related perceptions. Implications for instructors and researchers are provided.

This article reports on a unique collaboration between principal and teacher preparation programs within one college of education at a rural university in southeastern United States. The collaborative project worked to meet both the need of teacher candidates to receive instructional feedback and coaching on their teaching and the need of principal candidates to gain experience giving instructional coaching to novice teachers. Feedback and coaching were provided through video capture and annotation technology (VCAT) allowing the principal candidate to provide specific feedback using evidence from the teaching candidate's teaching video to support their instructional coaching. Researchers explored quantitative and qualitative data of principal candidates' coaching experience to determine the change in their self-efficacy in providing instructional coaching over the course of a semester and their perceptions of their experience using VCAT to facilitate the coaching.

Working conditions may be an important lever to support special educators' reading instruction for students with emotional and behavioral disorders (EBD). Thus, we explored how working conditions relate to the quality of special educators' reading instruction in upper-elementary, self-contained classes for students with EBD. Using mixed methods to examine video observations of reading instruction and varied data sources on working conditions, we found that special educators who provided stronger instruction had a partner coleading their program, and consistent paraprofessionals, with time and support for training. Partners and paraprofessionals, together, protected special educators' instruction time. Other conditions (i.e., material resources, role differentiation, role conceptions, planning time) emerged as potentially important, but evidence was less robust. Results indicate partners and paraprofessionals may be important forms of collegial support. These findings have important implications for improving the quality of instruction in self-contained settings for students with EBD.