Abstract
The Arctic is warming twice as fast as the rest of the planet, leading to rapid changes in species composition and plant functional trait variation. Landscape-level maps of vegetation ...composition and trait distributions are required to expand spatially-limited plot studies, overcome sampling biases associated with the most accessible research areas, and create baselines from which to monitor environmental change. Unmanned aerial vehicles (UAVs) have emerged as a low-cost method to generate high-resolution imagery and bridge the gap between fine-scale field studies and lower resolution satellite analyses. Here we used field spectroscopy data (400–2500 nm) and UAV multispectral imagery to test spectral methods of species identification and plant water and chemistry retrieval near Longyearbyen, Svalbard. Using the field spectroscopy data and Random Forest analysis, we were able to distinguish eight common High Arctic plant tundra species with 74% accuracy. Using partial least squares regression (PLSR), we were able to predict corresponding water, nitrogen, phosphorus and C:N values (
r
2
= 0.61–0.88, RMSEmean = 12%–64%). We developed analogous models using UAV imagery (five bands: Blue, Green, Red, Red Edge and Near-Infrared) and scaled up the results across a 450 m long nutrient gradient located underneath a seabird colony. At the UAV level, we were able to map three plant functional groups (mosses, graminoids and dwarf shrubs) at 72% accuracy and generate maps of plant chemistry. Our maps show a clear marine-derived fertility gradient, mediated by geomorphology. We used the UAV results to explore two methods of upscaling plant water content to the wider landscape using Sentinel-2A imagery. Our results are pertinent for high resolution, low-cost mapping of the Arctic.
More than 30 studies have examined the ability of scores on the Personality Assessment Inventory (PAI; Morey, 1991, 2007) to predict violence or misconduct. The Antisocial Features (ANT), Aggression ...(AGG), and Violence Potential Index (VPI) Scales of the PAI, in particular, have received substantial attention as predictors of institutional infractions and criminal recidivism. The current study used meta-analysis to provide a comprehensive review of the ability of scores on these and other PAI scales to predict misbehavior. Scores on the ANT (d = .26 to .39) and AGG (d = .23 to .40) scales consistently emerged as small to moderate predictors of misbehavior. Effects tended to be larger in correctional than treatment settings (e.g., ANT d = .44 vs. .20), for institutional misconduct than recidivism (e.g., AGG d = .37 vs. .23), and for institutional misconduct studies with follow up periods of at least 1.5 years (e.g., ANT d = .46). Overall, findings provide support for the predictive validity of multiple PAI scales.
This study describes the feasibility and accuracy of a novel computed tomography (CT) fractional flow reserve (FFR) technique based on alternative boundary conditions.
Techniques used to compute FFR ...based on images acquired from coronary computed tomography angiography (CTA) are described. Boundary conditions were typically determined by allometric scaling laws and assumptions regarding microvascular resistance. Alternatively, boundary conditions can be derived from the structural deformation of coronary lumen and aorta, although its accuracy remains unknown.
Forty-two patients (78 vessels) in a single institution prospectively underwent 320-detector coronary CTA and FFR. Deformation of coronary cross-sectional lumen and aorta, computed from coronary CTA images acquired over diastole, was used to determine the boundary conditions based on hierarchical Bayes modeling. CT-FFR was derived using a reduced order model performed using a standard desktop computer and dedicated software. First, 12 patients (20 vessels) formed the derivation cohort to determine optimal CT-FFR threshold with which to detect functional stenosis, defined as FFR of ≤0.8, which was validated in the subsequent 30 patients (58 vessels).
Derivation cohort results demonstrated optimal threshold for CT-FFR was 0.8 with 67% sensitivity and 91% specificity. In the validation cohort, CT-FFR was successfully computed in 56 of 58 vessels (97%). Compared with coronary CTA, CT-FFR at ≤0.8 demonstrated a higher specificity (87% vs. 74%, respectively) and positive predictive value (74% vs. 60%, respectively), with comparable sensitivity (78% vs. 79%, respectively), negative predictive value (89% vs. 88%, respectively), and accuracy (area under the curve: 0.88 vs. 0.77, respectively; p = 0.22). Based on Bland-Altman analysis, mean intraobserver and interobserver variability values for CT-FFR were, respectively, -0.02 ± 0.05 (95% limits of agreement: -0.12 to 0.08) and 0.03 ± 0.06 (95% limits: 0.07 to 0.19). Mean time per patient for CT-FFR analysis was 27.07 ± 7.54 min.
CT-FFR based on alternative boundary conditions and reduced-order fluid model is feasible, highly reproducible, and may be accurate in detecting FFR ≤ 0.8. It requires a short processing time and can be completed at point-of-care. Further validation is required in large prospective multicenter settings.
Triple-negative breast cancer (TNBC) is an aggressive and highly metastatic type of tumor. TNBC is often enriched in tumor-infiltrating neutrophils (TINs), which support cancer growth in part by ...counteracting tumor-infiltrating lymphocytes (TILs). Prior studies identified the enhancer of zeste homolog 2 (EZH2) as a pro-tumor methyltransferase in primary and metastatic TNBCs. We hypothesized that EZH2 inhibition in TNBC cells per se would exert antitumor activity by altering the tumor immune microenvironment. To test this hypothesis, we used CRISPR to generate
gene knockout (KO) and overexpressing (OE) lines from parent (wild-type-WT) 4T1 cells, an established murine TNBC model, resulting in EZH2 protein KO and OE, respectively. In vitro, EZH2 KO and OE cells showed early, transient changes in replicative capacity and invasiveness, and marked changes in surface marker profile and cytokine/chemokine secretion compared to WT cells. In vivo, EZH2 KO cells showed significantly reduced primary tumor growth and a 10-fold decrease in lung metastasis compared to WT cells, while EZH2 OE cells were unchanged. Compared to WT tumors, TIN:TIL ratios were greatly reduced in EZH2 KO tumors but unchanged in EZH2 OE tumors. Thus, EZH2 is key to 4T1 aggressiveness as its tumor-intrinsic knockout alters their in vitro secretome and in vivo primary tumor growth, TIN/TIL poise, and metastasis.
Acute myeloid leukemia (AML) is an aggressive disease with a poor prognosis (5-year survival rate of 30.5% in the United States). Designing cell therapies to target AML is challenging because no ...single tumor-associated antigen (TAA) is highly expressed on all cancer subpopulations. Furthermore, TAAs are also expressed on healthy cells, leading to toxicity risk. To address these targeting challenges, we engineer natural killer (NK) cells with a multi-input gene circuit consisting of chimeric antigen receptors (CARs) controlled by OR and NOT logic gates. The OR gate kills a range of AML cells from leukemic stem cells to blasts using a bivalent CAR targeting FLT3 and/or CD33. The NOT gate protects healthy hematopoietic stem cells (HSCs) using an inhibitory CAR targeting endomucin, a protective antigen unique to healthy HSCs. NK cells with the combined OR-NOT gene circuit kill multiple AML subtypes and protect primary HSCs, and the circuit also works in vivo.
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•A three-input logic gate with activating and inhibitory CARs is optimized in NK cells•Logic-gated NK cells kill leukemic stem cells and blasts, not healthy stem cells•Selective killing of tumor cells is validated in vivo in a mixed target cell model
Treating acute myeloid leukemia with conventional, single-target CAR cell therapies is challenging due to tumor heterogeneity and because tumor antigens are found on hematopoietic stem cells. Frankel et al. design logic-gated CAR-natural killer cells that simultaneously detect three antigens on prospective target cells to safely decide whether to kill them.
Background
This study was aimed at developing and validating a decision‐making tool predictive of overall survival (OS) for patients receiving stereotactic body radiation therapy (SBRT) for spinal ...metastases.
Methods
Three hundred sixty‐one patients at one institution were used for the training set, and 182 at a second institution were used for external validation. Treatments most commonly involved one or three fractions of spine SBRT. Exclusion criteria included proton therapy and benign histologies.
Results
The final model consisted of the following variables and scores: Spinal Instability Neoplastic Score (SINS) ≥ 6 (1), time from primary diagnosis < 21 months (1), Eastern Cooperative Oncology Group (ECOG) performance status = 1 (1) or ECOG performance status > 1 (2), and >1 organ system involved (1). Each variable was an independent predictor of OS (p < .001), and each 1‐point increase in the score was associated with a hazard ratio of 2.01 (95% confidence interval CI, 1.79–2.25; p < .0001). The concordance value was 0.75 (95% CI, 0.71–0.78). The scores were discretized into three groups—favorable (score = 0–1), intermediate (score = 2), and poor survival (score = 3–5)—with 2‐year OS rates of 84% (95% CI, 79%–90%), 46% (95% CI, 36%–59%), and 21% (95% CI, 14%–32%), respectively (p < .0001 for each). In the external validation set (182 patients), the score was also predictive of OS (p < .0001). Increasing SINS<zaq;6> was predictive of decreased OS as a continuous variable (p < .0001).
Conclusions
This novel score is proposed as a decision‐making tool to help to optimize patient selection for spine SBRT. SINS may be an independent predictor of OS.
A model predictive of overall survival after spine stereotactic body radiation therapy (SBRT) has been developed and externally validated, and it provides a decision‐making tool to help to optimize patient selection for spine SBRT. The model components are the Spinal Instability Neoplastic Score, the time from diagnosis, the performance status, and the organ systems involved.
Objectives The goal of this study was to compare the diagnostic accuracy of combined computed tomography perfusion (CTP) + computed tomography angiography (CTA), transluminal attenuation gradient by ...320-detector row computed tomography (TAG320) + CTA, and CTP + TAG320 + CTA (multidetector computed tomography–integrated protocol MDCT-IP) assessment in predicting significant fractional flow reserve (FFR). Background CTA has limited specificity for predicting functionally significant stenoses. Novel CT techniques, including adenosine stress CTP and TAG320, may improve the diagnostic accuracy of CTA. Methods CTA, CTP, and TAG320 were assessed using 320-detector row MDCT. Patients who underwent CTA, CTP, and FFR assessment on invasive coronary angiography were included. CTP was assessed using the visual perfusion assessment. TAG320 was defined as the linear regression coefficient between luminal attenuation and axial distance. A TAG320 cutoff value of −15.1 HU/10 mm as previously described was defined as significant. Functionally significant coronary stenosis was defined as FFR ≤0.8. Results The cohort included 75 patients (age 64.1 ± 10.8 years, 52 men) and 44 (35%) FFR-significant vessels. In 127 vessels, CTA predicted FFR-significant stenosis with 89% sensitivity and 65% specificity compared with MDCT-IP, which showed 88% sensitivity and 83% specificity. In 97 vessels in which the results of all techniques were available, TAG320 + CTA (area under the curve AUC = 0.844) and CTP + CTA (AUC = 0.845) had comparable per-vessel diagnostic accuracy (p = 0.98). The diagnostic accuracy of MDCT-IP (AUC = 0.91) was superior to TAG320 + CTA or CTP + CTA (p = 0.01). Conclusions In vessels without significant calcification or artefact, TAG320 + CTA and CTP + CTA provide comparable diagnostic accuracy for functional assessment of coronary artery stenosis. MDCT-IP may provide the best diagnostic accuracy for functional assessment of coronary artery stenosis.
Prior authorization is a process that health insurance companies use to determine if a patient’s health insurance will cover certain medical treatments, procedures, or medications. Prior ...authorization requests are common in adult congenital and pediatric cardiology (ACPC) due to need for advanced diagnostics, complex procedures, disease-specific medications, and the heterogeneity of the ACPC population. Prior authorizations in ACPC are rarely denied, but nonetheless, they are often accompanied by significant administrative burden on clinical care teams and delays in patient care. Prior authorizations have been implicated in worsening care inequities. The prior authorization process is insurer specific with differences between commercial and public insurers. Prior authorization rejections were previously found to be more common for women, racial minorities, those with low education, and in low-income groups. Prior authorization unduly burdens routine diagnostics, routine interventional and surgical procedures, and routine cardiac specific medication use in the ACPC population. This manuscript highlights the burdens of prior authorization and advocates for the elimination of prior authorization for ACPC patients.
We present a case of a young boy who developed persistent tachycardia despite fluid resuscitation, antipyretics, and analgesia after a Fontan procedure. Review of telemetry and ECGs revealed ...repolarization abnormalities, including the appearance of T-wave alternans, for which an uncommon cause was ultimately identified.
Objectives
To evaluate whether a novel definition of spirometric respiratory impairment from the Global Lung Initiative (GLI) is strongly associated with respiratory symptoms and, in turn, frequently ...establishes symptomatic respiratory disease.
Design
Cross‐sectional.
Setting
Third National Health and Nutrition Examination Survey.
Participants
Community‐dwelling individuals aged 40 to 80 (N = 7,115).
Measurements
GLI‐defined spirometric respiratory impairment (airflow obstruction and restrictive pattern), dyspnea on exertion (DOE), chronic bronchitis (CB), and wheezing.
Results
Prevalence rates were 12.7% for airflow obstruction, 6.2% for restrictive pattern, 28.6% for DOE, 12.6% for CB, and 12.9% for wheezing. Airflow obstruction was associated with DOE (adjusted odds ratio (aOR) = 1.69, 95% confidence interval (CI) = 1.42–2.02), CB (aOR = 1.92, 95% CI = 1.62–2.29), and wheezing (aOR = 2.50, 95% CI = 2.08–3.00), and restrictive pattern was associated with DOE (aOR = 1.75, 95% CI = 1.36–2.25), CB (aOR = 1.39, 95% CI = 1.08–1.78), and wheezing (aOR = 1.53, 95% CI = 1.15–2.04). Nonetheless, among participants who had airflow obstruction and restrictive pattern, only a minority had DOE (38.6% and 45.5%), CB (23.3% and 15.9%), and wheezing (24.4% and 19.1%), yielding a positive predictive value (PPV) of only 53% for any respiratory symptom in the setting of any spirometric respiratory impairment. In addition, most participants who had DOE (73.0%), CB (67.8%), and wheezing (66.8%) did not have airflow obstruction or restrictive pattern, yielding a PPV of only 26% for any spirometric respiratory impairment in the setting of any respiratory symptom. The results differed only modestly when stratified according to age (40–64 vs 65–80).
Conclusion
GLI‐defined spirometric respiratory impairment increased the likelihood of respiratory symptoms but was nonetheless a poor predictor of respiratory symptoms. Similarly, respiratory symptoms were poor predictors of GLI‐defined spirometric respiratory impairment. Hence, a comprehensive assessment is needed when evaluating respiratory symptoms, even in the presence of spirometric respiratory impairment.
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