Response of Obligate Birds to Mechanical Manipulations in a Sagebrush Ecosystem Near Gunnison, Colorado

Sagebrush ecosystems across western North America have declined in productivity and biodiversity with significant declines in sagebrush obligate birds. Mechanical methods to reduce sagebrush canopy cover and encourage herbaceous undergrowth have been implemented to restore sagebrush ecosystems. How these treatments affect sagebrush obligate birds has not been documented. In this study, we hypothesized that nesting success would decline in mechanically treated (mowed and dixie harrowed) plots immediately and for two years after treatment. Twelve 6-ha plots within the South Parlin Common Allotment in the Gunnison Basin, Colorado were established in 2005. Four replicates of untreated (control), mowed and disked (dixie harrow) plots were sampled in 2005 (pre-treatment) and in 2006 and 2007. We located nests using the systematic walk and incidental flush method. We revisited nests every three to five days to determine nest fate. We located 142 nests of nine species in 90 nest searches and expended over 600 man hours. Mayfield nest success (proportion of nests that successfully hatch at least one young) and clutch size were similar among treatments. Nest success of artificial nests also was similar among treatments. Predation was the leading cause of nest failure accounting for 71 to 77 percent of all nest failures and small mammals were implicated in 76 percent of the depredations. Least chipmunks may have been the principle predator of sagebrush bird nests in our study. Small scale mechanical treatments to restore sagebrush apparently do not negatively affect sagebrush birds within two years post-treatment, but longer duration studies and larger sample sizes are required to better assess the impact of treatments on sagebrush avifauna

Dosimetric Consequences of 3D Versus 4D PET/CT for Target Delineation of Lung Stereotactic Radiotherapy

Introduction:Lung tumor delineation is frequently performed using 3D positron emission tomography (PET)/computed tomography (CT), particularly in the radiotherapy treatment planning position, by generating an internal target volume (ITV) from the slow acquisition PET. We investigate the dosimetric consequences of stereotactic ablative body radiotherapy (SABR) planning on 3D PET/CT in comparison with gated (4D) PET/CT.Methods:In a prospective clinical trial, patients with lung metastases were prescribed 26 Gy single-fraction SABR to the covering isodose. Contemporaneous 3D PET/CT and 4D PET/CT was performed in the same patient position. An ITV was generated from each data set, with the planning target volume (PTV) being a 5-mm isotropic expansion. Dosimetric parameters from the SABR plan derived using the 3D volumes were evaluated against the same plan applied to 4D volumes.Results:Ten lung targets were evaluated. All 3D plans were successfully optimized to cover 99% of the PTV by the 26 Gy prescription. In all cases, the calculated dose delivered to the 4D target was less than the expected dose to the PTV based on 3D planning. Coverage of the 4D-PTV by the prescription isodose ranged from 74.48% to 98.58% (mean of 90.05%). The minimum dose to the 4D-ITV derived by the 3D treatment plan (mean = 93.11%) was significantly lower than the expected dose to ITV based on 3D PET/CT calculation (mean = 111.28%), p < 0.01. In all but one case, the planned prescription dose did not cover the 4D-PET/CT derived ITV.Conclusions:Target delineation using 3D PET/CT without additional respiratory compensation techniques results in significant target underdosing in the context of SABR

Renal Survival in Children with Glomerulonephritis with Crescents: A Pediatric Nephrology Research Consortium Cohort Study

There is no evidence-based definition for diagnosing crescentic glomerulonephritis. The prognostic implications of crescentic lesions on kidney biopsy have not been quantified. Our objective was to determine risk factors for end-stage kidney disease (ESKD) in patients with glomerulonephritis and crescents on kidney biopsy. A query of the Pediatric Nephrology Research Consortium’s Pediatric Glomerulonephritis with Crescents registry identified 305 patients from 15 centers. A retrospective cohort study was performed with ESKD as the primary outcome. Median age at biopsy was 11 years (range 1–21). The percentage of crescents was 3–100% (median 20%). Etiologies included IgA nephropathy (23%), lupus (21%), IgA vasculitis (19%) and ANCA-associated GN (13%), post-infectious GN (5%), and anti-glomerular basement membrane disease (3%). The prevalence of ESKD was 12% at one year and 16% at last follow-up (median = 3 years, range 1–11). Median time to ESKD was 100 days. Risk factors for ESKD included %crescents, presence of fibrous crescents, estimated GFR, and hypertension at biopsy. For each 1% increase in %crescents, there was a 3% decrease in log odds of 1-year renal survival (p = 0.003) and a 2% decrease in log odds of renal survival at last follow-up (p \u3c 0.001). These findings provide an evidence base for enrollment criteria for crescentic glomerulonephritis in future clinical trials

AMPK Is Essential to Balance Glycolysis and Mitochondrial Metabolism to Control T-ALL Cell Stress and Survival

T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy associated with Notch pathway mutations. While both normal activated and leukemic T cells can utilize aerobic glycolysis to support proliferation, it is unclear to what extent these cell populations are metabolically similar and if differences reveal T-ALL vulnerabilities. Here we show that aerobic glycolysis is surprisingly less active in T-ALL cells than proliferating normal T cells and that T-ALL cells are metabolically distinct. Oncogenic Notch promoted glycolysis but also induced metabolic stress that activated 5' AMP-activated kinase (AMPK). Unlike stimulated T cells, AMPK actively restrained aerobic glycolysis in T-ALL cells through inhibition of mTORC1 while promoting oxidative metabolism and mitochondrial Complex I activity. Importantly, AMPK deficiency or inhibition of Complex I led to T-ALL cell death and reduced disease burden. Thus, AMPK simultaneously inhibits anabolic growth signaling and is essential to promote mitochondrial pathways that mitigate metabolic stress and apoptosis in T-ALL

Efficacy and safety of avapritinib in advanced systemic mastocytosis:interim analysis of the phase 2 PATHFINDER trial

Advanced systemic mastocytosis (AdvSM) is a rare, KIT D816V-driven hematologic neoplasm characterized by mast cell infiltration and shortened survival. We report the results of a prespecified interim analysis of an ongoing pivotal single-arm phase 2 trial (no. NCT03580655) of avapritinib, a potent, selective KIT D816V inhibitor administered primarily at a once-daily starting dose of 200 mg in patients with AdvSM (n = 62). The primary endpoint was overall response rate (ORR). Secondary endpoints included mean baseline change in AdvSM–Symptom Assessment Form Total Symptom Score and quality of life, time to response, duration of response, progression-free survival, overall survival, changes in measures of disease burden and safety. The primary endpoint was successfully met (P = 1.6 × 10(-9)), with an ORR of 75% (95% confidence interval 57–89) in 32 response-evaluable patients with AdvSM who had sufficient follow-up for response assessment, including 19% with complete remission with full or partial hematologic recovery. Reductions of ≥50% from baseline in serum tryptase (93%), bone marrow mast cells (88%) and KIT D816V variant allele fraction (60%) were observed. The most frequent grade ≥3 adverse events were neutropenia (24%), thrombocytopenia (16%) and anemia (16%). Avapritinib demonstrated a high rate of clinical, morphological and molecular responses and was generally well tolerated in patients with AdvSM

Landsat 9 Thermal Infrared Sensor 2 Architecture and Design

The Thermal Infrared Sensor 2 (TIRS-2) will fly aboard the Landsat 9 spacecraft and leverages the Thermal Infrared Sensor (TIRS) design currently flying on Landsat 8. TIRS-2 will provide similar science data as TIRS, but is not a buildto-print rebuild due to changes in requirements and improvements in absolute accuracy. The heritage TIRS design has been modified to reduce the influence of stray light and to add redundancy for higher reliability over a longer mission life. The TIRS-2 development context differs from the TIRS scenario, adding to the changes. The TIRS-2 team has also learned some lessons along the way

Investigating variation in replicability

Although replication is a central tenet of science, direct replications are rare in psychology. This research tested variation in the replicability of 13 classic and contemporary effects across 36 independent samples totaling 6,344 participants. In the aggregate, 10 effects replicated consistently. One effect – imagined contact reducing prejudice – showed weak support for replicability. And two effects – flag priming influencing conservatism and currency priming influencing system justification – did not replicate. We compared whether the conditions such as lab versus online or US versus international sample predicted effect magnitudes. By and large they did not. The results of this small sample of effects suggest that replicability is more dependent on the effect itself than on the sample and setting used to investigate the effect

Aligning the Goals of Learning Analytics with its Research Scholarship: An Open Peer Commentary Approach

To promote cross-community dialogue on matters of significance within the field of learning analytics], we as editors-in- chief of the Journal of Learning Analytics have introduced a section for papers that are open to peer commentary. The first of these papers, “A LAK of Direction: Misalignment Between the Goals of Learning Analytics and its Research Scholarship” by Motz et al. (2023), appeared in the journal’s early access section in March 2023, a few days before the start of the 13th International Learning Analytics and Knowledge Conference (LAK ’23). “A LAK of Direction” takes as its starting point the definition of learning analytics used in the call for papers of the first LAK conference (LAK ’11) and used since then by the Society for Learning Analytics Research (SoLAR): “Learning analytics is the measurement, collection, analysis and reporting of data about learners and their contexts, for purposes of understanding and optimizing learning and the environments in which it occurs” (Long & Siemens, 2011, p. 24). Following the conference, an invitation to submit proposals for commentaries on the paper was released, and 12 of these proposals were accepted. This paper brings those commentaries togethe