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Background Medical practitioners use survival models to explore and understand the relationships between patients’ covariates (e.g. clinical and genetic features) and the effectiveness of various treatment options. Standard survival models like the linear Cox proportional hazards model require extensive feature engineering or prior medical knowledge to model treatment interaction at an individual level. While nonlinear survival methods, such as neural networks and survival forests, can inherently model these high-level interaction terms, they have yet to be shown as effective treatment recommender systems. Methods We introduce DeepSurv, a Cox proportional hazards deep neural network and state-of-the-art survival method for modeling interactions between a patient’s covariates and treatment effectiveness in order to provide personalized treatment recommendations. Results We perform a number of experiments training DeepSurv on simulated and real survival data. We demonstrate that DeepSurv performs as well as or better than other state-of-the-art survival models and validate that DeepSurv successfully models increasingly complex relationships between a patient’s covariates and their risk of failure. We then show how DeepSurv models the relationship between a patient’s features and effectiveness of different treatment options to show how DeepSurv can be used to provide individual treatment recommendations. Finally, we train DeepSurv on real clinical studies to demonstrate how it’s personalized treatment recommendations would increase the survival time of a set of patients. Conclusions The predictive and modeling capabilities of DeepSurv will enable medical researchers to use deep neural networks as a tool in their exploration, understanding, and prediction of the effects of a patient’s characteristics on their risk of failure.

There is limited knowledge of grazing impacts on longer term plant community dynamics following fire in sagebrush steppe. This study evaluated vegetation response to different intensities of deferred rotation cattle grazing over 16 years (2007–2022) on burned Wyoming big sagebrush ( Artemisia tridentata ssp. wyomingensis (Beetle & Young) Welsh) steppe in eastern Oregon. Treatments were applied in a randomized complete block, which included no grazing on burned (nonuse, n  = 5) and unburned (control, n  = 5) steppe; and cattle grazing at low (low, n  = 4), moderate (moderate, n  = 4), and high (high, n  = 4) intensities on burned steppe. Vegetation dynamics were evaluated by repeated measures analysis of canopy cover and density of shrub and herbaceous species and functional groups. Herbaceous functional groups were an early‐season bunchgrass (one species, Sandberg bluegrass [ Poa secunda J. Presl]), tall perennial bunchgrasses, perennial forbs, annual grass (one species, cheatgrass [ Bromus tectorum L.]), and annual forbs. Tall perennial bunchgrass, Sandberg bluegrass, and perennial forb cover and density did not differ among the treatments but did decrease over time in all treatments. The cover of several tall bunchgrass species was generally less in the high treatment, mainly, Idaho fescue ( Festuca idahoensis Elmer) and Thurber's needlegrass ( Achnatherum thurberianum (Piper) Barkworth). The cover of cheatgrass and annual forbs varied among years but was greater in the burned‐grazed and nonuse treatments than in the control. Native plant cover in the burned treatments (grazed and nonuse) represented 77%–85% of total herbaceous cover versus the control where native plants comprised 91% of the total. Annual weather variability appears to account for most of the compositional dynamics measured in the various grazed and ungrazed treatments.

We assessed plant community succession following prescribed fire on ungrazed Wyoming big sagebrush steppe, eastern Oregon. Treatments were burned (Burn; September and October, 2002) and unburned (Control) sagebrush steppe. Herbaceous yield, vegetation canopy cover and density were compared between treatments after fire (2003–18). Herbaceous yield in the Burn treatment was about double the Control for most of the study period. Prior to fire, native perennials comprised 90–95% of herbaceous yield. After fire, native perennials represented 78% (range 67–93%) and exotic annuals 22% (range 7–33%) of total yield. Exotic annuals increased after fire and responded in two stages. In the first 8 years after fire, desert alyssum dominated the annual plant composition. In the last half of the study, cheatgrass co-dominated the annual component with alyssum. Sagebrush recovery was slow and we estimated sagebrush cover would return to pre-burn levels, at the earliest, in 115 years. Burning Wyoming big sagebrush steppe would be detrimental to sagebrush-obligate wildlife for an extended time period, because of lost cover and structure provided by sagebrush. The additional forage provided on burned areas may give livestock manager’s greater flexibility to rest or defer unburned habitat for wildlife species of critical concern.

Understanding the effects of contemporary cattle grazing on herbaceous perennial communities in big sagebrush steppe is important for managing for wildlife habitat, plant diversity, and productivity, yet potentially complicated by legacy impacts of historic, often higher intensity, livestock grazing. Here, we evaluate whether recovery of herbaceous communities in eastern Oregon, USA, after the cessation of intense spring sheep grazing (1935) was affected by moderate cattle grazing in paired plots with or without grazing over the past 75 yr (1936–2011). We tested for the effects of cattle grazing on herbaceous community recovery, as indicated by changes over time in plant density, and composition, as measured by Bray–Curtis dissimilarity. We also included current and prior to sampling year precipitation anomalies, to account for the weather effects, and a random term for pasture location of plot pairs to include potential subtle differences in abiotic environment and grazing management. We further tested whether time since cessation of intense sheep grazing and moderate cattle grazing were associated with convergence or divergence in community composition indicated by changes in evenness, richness, species relative abundance (rank order), and turnover or species appearance or disappearance. Total perennial herbaceous, forb, and grass density increased over time in sites grazed and ungrazed by cattle, though species varied in the direction of their response to contemporary cattle grazing. Community composition metrics indicated convergence over time including increasing evenness, decreasing Bray–Curtis dissimilarity, decreasing shifts in species relative abundance (rank order), and lower rates of species turnover (and gain and loss). Contemporary cattle grazing was not associated with convergence or divergence in composition. Precipitation anomalies for the current or prior water year were only occasionally significant in herbaceous density and community composition change models. Our results indicate similar long‐term recovery trajectories occurred in sites with moderate cattle grazing or removal of all livestock following cessation of intense sheep grazing. Management planning and resource assessment focused on herbaceous perennial communities in sagebrush steppe should seek to separate the impacts of historic from contemporary livestock grazing practices.

We evaluated plant community succession following prescribed fire on Artemisia arbuscula var. arbuscula (Nutt.) McMinn (low sagebrush) steppe in southeastern Oregon. Treatments were “prescribed burned” (burn; fall 2012) and “unburned” (control) A. arbuscula steppe, and the study design was a randomized complete block with 4 replicates per treatment. Herbaceous yield and vegetation canopy cover and density were compared between treatments (2012–2020). Fire practically eliminated A. arbuscula and there was no recruitment of new plants in the first 8 years after burning. Herbaceous yield in the burn treatment was about double the control for most of the postfire period. Native perennial grasses and forbs constituted 94% to 96% and Bromus tectorum L. (cheatgrass) 0.2% to 2% of total herbaceous yield in the control. In the burn treatment, perennial grasses and forbs constituted 83% to 87%, native annual forbs 2% to 5%, and B. tectorum 3% to 9% of total herbaceous yield. Despite an increase in B. tectorum, the burned A. arbuscula sites were dominated by herbaceous perennial grasses and forbs and exhibited high levels of resilience and resistance. After prescribed fire, for the study sites and comparable A. arbuscula associations, weed control or seeding are not necessary to recover the native herbaceous community. However, the results in our study are for low-severity prescribed fire in intact A. arbuscula plant communities. Higher-severity fire, as might occur with wildfire, and in A. arbuscula communities having greater prefire invasive weed composition should not be assumed to develop similarly high levels of community resilience and resistance.

The stromal cell derived factor (SDF)-1/chemokine receptor (CXCR)-4 signaling pathway plays a key role in lung cancer metastasis and is molecular target for therapy. In the present study we investigated whether interleukin (IL)-24 can inhibit the SDF-1/CXCR4 axis and suppress lung cancer cell migration and invasion in vitro. Further, the efficacy of IL-24 in combination with CXCR4 antagonists was investigated. Human H1299, A549, H460 and HCC827 lung cancer cell lines were used in the present study. The H1299 lung cancer cell line was stably transfected with doxycycline-inducible plasmid expression vector carrying the human IL-24 cDNA and used in the present study to determine the inhibitory effects of IL-24 on SDF-1/CXCR4 axis. H1299 and A549 cell lines were used in transient transfection studies. The inhibitory effects of IL-24 on SDF1/CXCR4 and its downstream targets were analyzed by quantitative RT-PCR, western blot, luciferase reporter assay, flow cytometry and immunocytochemistry. Functional studies included cell migration and invasion assays. Endogenous CXCR4 protein expression levels varied among the four human lung cancer cell lines. Doxycycline-induced IL-24 expression in the H1299-IL24 cell line resulted in reduced CXCR4 mRNA and protein expression. IL-24 post-transcriptionally regulated CXCR4 mRNA expression by decreasing the half-life of CXCR4 mRNA (>40%). Functional studies showed IL-24 inhibited tumor cell migration and invasion concomitant with reduction in CXCR4 and its downstream targets (pAKTS473, pmTORS2448, pPRAS40T246 and HIF-1α). Additionally, IL-24 inhibited tumor cell migration both in the presence and absence of the CXCR4 agonist, SDF-1. Finally, IL-24 when combined with CXCR4 inhibitors (AMD3100, SJA5) or with CXCR4 siRNA demonstrated enhanced inhibitory activity on tumor cell migration. IL-24 disrupts the SDF-1/CXCR4 signaling pathway and inhibits lung tumor cell migration and invasion. Additionally, IL-24, when combined with CXCR4 inhibitors exhibited enhanced anti-metastatic activity and is an attractive therapeutic strategy for lung metastasis.

Woodland ecosystems of the world have been changed by land use demands, altered fire regimes, invasive species and climate change. Reduced fire frequency is recognised as a main causative agent for Pinus–Juniperus L. (piñon–juniper) expansion in North American woodlands. Piñon–juniper control measures, including prescribed fire, are increasingly employed to restore sagebrush steppe communities. We compared vegetation recovery following prescribed fire on Phase 2 (mid-succession) and Phase 3 (late-succession) Juniperus occidentalis Hook. (western juniper) woodlands in Oregon. The herbaceous layer on Phase 2 sites was comprised of native perennial and annual vegetation before and after fire. On Phase 3 sites the herbaceous layer shifted from native species to dominance by invasive Bromus tectorum L. (cheatgrass). After fire, shrubs on Phase 2 sites were comprised of sprouting species and Ceanothus velutinus Dougl. (snowbrush). On Phase 3 woodland sites the shrub layer was dominated by C. velutinus. The results suggest that Phase 2 sites have a greater likelihood of recovery to native vegetation after fire and indicate that sites transitioning from Phase 2 to Phase 3 woodlands cross a recovery threshold where there is a greater potential for invasive weeds, rather than native vegetation, to dominate after fire.

Describing relationships among weather variables and herbage yield is important for planning livestock grazing, assessing wildlife habitat, and evaluating short and longterm vegetation dynamics. We investigated the effects of weather on herbage yields from 44 Wyoming big sagebrush (Artemisia tridentata subsp. wyomingensis Beetle & Young) steppe sites across eastern Oregon from 2003 to 2012. We used linear and multiple linear regression to relate herbaceous total and functional group yields to monthly and seasonal precipitation, reference evapotranspiration (RET), and temperature. Functional groups were large perennial bunchgrasses, Sandberg bluegrass (Poa secunda J. Presl.), perennial forbs, annual forbs, and annual grasses. Yields and weather variables were normalized prior to regression analysis to account for differences in site characteristics. Normalized variables were obtained by dividing yield and weather variables by their 10year means. Fallthroughspring (e.g., October–May, September–May) and spring precipitation and RET all contributed to significant predictive models for both functional groups and total herbage. Spring precipitation provided the strongest predictor of perennial bunchgrasses (March–May and June; R2 = 0.91), perennial forbs (May; R2 = 0.79), annual grasses (March; R2 = 0.79), and total herbage (March–May; R2 = 0.83) yields. Yields of Sandberg bluegrass and annual forbs were most strongly associated with RET for October–May (R2 = 0.86) and October–April (R2 = 0.79), respectively. Overall, we found a greater influence of latewinter and spring precipitation than that of models developed several decades ago where cropyear (September–June) precipitation provided more accurate herbage biomass estimates. Describir la relación de las variables climáticas y las de producción de forraje es importante para planificar el pastoreo del ganado, evaluar el hábitat de la vida silvestre y la dinámica de la vegetación a corto y largo plazo. Investigamos los efectos del clima en el forraje de 44 sitios esteparios de artemisa grande de Wyoming (Artemisia tridentata subsp. wyomingensis Beetle & Young) en todo el este de Oregón entre 2003 y 2012. Utilizamos regresión lineal y lineal múltiple para relacionar la producción total y los grupos funcionales herbáceos con la precipitación mensual y estacional, la evapotranspiración de referencia (RET, por sus siglas en inglés) y la temperatura. Los grupos funcionales fueron: pasto perenne grande, Sandberg bluegrass (Poa secunda J. Presl.), hierba perenne, hierba y pasto anuales. Las variables de producción y climáticas se normalizaron antes del análisis de regresión con el propósito de controlar las diferencias en las características de los sitios. Las variables normalizadas se obtuvieron dividiendo las variables de producción y climáticas por su promedio de los últimos 10 años. Del otoño hasta la primavera (es decir, octubre–mayo, septiembre–mayo), la precipitación de primavera y la RET contribuyeron en la obtención de modelos predictivos significativos tanto para los grupos funcionales como para el forraje total. La precipitación de primavera proporcionó el mejor indicador de la producción de pasto perenne (marzo–mayo y junio; R2 = 0.91), hierba perenne (mayo; R2 = 0.79), pasto anual (marzo; R2 = 0.79), y forraje total (marzo–mayo; R2 = 0.83). La producción de Sandberg bluegrass y de herbáceas anuales se asociaron más con la RET en octubre–mayo (R2 = 0.86) y octubre–abril (R2 = 0.79), respectivamente. En general, encontramos una mayor influencia de las precipitaciones de finales de invierno y primavera que los modelos presentados hace varias décadas, donde la precipitación del año de cosecha (septiembre a junio) proporcionó estimaciones más precisas de la biomasa del forraje.

ObjectiveVenous thromboembolism (VTE) risk reduction strategies include early initiation of chemoprophylaxis, reducing missed doses, weight-based dosing and dose adjustment using anti-Xa levels. We hypothesized that time to initiation of chemoprophylaxis would be the strongest modifiable risk for VTE, even after adjusting for competing risk factors.MethodsA prospectively maintained trauma registry was queried for patients admitted July 2017–October 2021 who were 18 years and older and received emergency release blood products. Patients with deep vein thrombosis or pulmonary embolism (VTE) were compared to those without (no VTE). Door-to-prophylaxis was defined as time from hospital arrival to first dose of VTE chemoprophylaxis (hours). Univariate and multivariate analyses were then performed between the two groups.Results2047 patients met inclusion (106 VTE, 1941 no VTE). There were no differences in baseline or demographic data. VTE patients had higher injury severity score (29 vs 24), more evidence of shock by arrival lactate (4.6 vs 3.9) and received more post-ED transfusions (8 vs 2 units); all p<0.05. While there was no difference in need for enoxaparin dose adjustment or missed doses, door-to-prophylaxis time was longer in the VTE group (35 vs 25 hours; p=0.009). On multivariate logistic regression analysis, every hour delay from time of arrival increased likelihood of VTE by 1.5% (OR 1.015, 95% CI 1.004 to 1.023, p=0.004).ConclusionThe current retrospective study of severely injured patients with trauma who required emergency release blood products found that increased door-to-prophylaxis time was significantly associated with an increased likelihood for VTE. Chemoprophylaxis initiation is one of the few modifiable risk factors available to combat VTE, therefore early initiation is paramount. Similar to door-to-balloon time in treating myocardial infarction and door-to-tPA time in stroke, “door-to-prophylaxis time” should be considered as a hospital metric for prevention of VTE in trauma.Level of evidenceLevel III, retrospective study with up to two negative criteria.

The expansion of piñon–juniper woodlands the past 100 years in the western United States has resulted in large scale efforts to kill trees and recover sagebrush steppe rangelands. It is important to evaluate vegetation recovery following woodland control to develop best management practices. In this study, we compared two fuel reduction treatments and a cut-and-leave (CUT) treatment used to control western juniper ( Juniperus occidentalis spp. occidentalis Hook.) of the northwestern United States. Treatments were; CUT, cut-and-broadcast burn (BURN), and cut-pile-and-burn the pile (PILE). A randomized complete block design was used with five replicates of each treatment located in a curl leaf mahogany ( Cercocarpus ledifolius Nutt. ex Torr. & A. Gray)/mountain big sagebrush ( Artemisia tridentata Nutt. spp. vaseyana (Rydb.) Beetle)/Idaho fescue ( Festuca idahoensis Elmer) association. In 2010, 4 years after tree control the cover of perennial grasses (PG) [Sandberg’s bluegrass ( Poa secunda J. Pres) and large bunchgrasses] were about 4 and 5 % less, respectively, in the BURN (7.1 ± 0.6 %) than the PILE (11.4 ± 2.3 %) and CUT (12.4 ± 1.7 %) treatments ( P  < 0.0015). In 2010, cover of invasive cheatgrass ( Bromus tectorum L.) was greater in the BURN (6.3 ± 1.0 %) and was 50 and 100 % greater than PILE and CUT treatments, respectively. However, the increase in perennial bunchgrass density and cover, despite cheatgrass in the BURN treatment, mean it unlikely that cheatgrass will persist as a major understory component. In the CUT treatment mahogany cover increased 12.5 % and density increased in from 172 ± 25 to 404 ± 123 trees/ha. Burning, killed most or all of the adult mahogany, and mahogany recovery consisted of 100 and 67 % seedlings in the PILE and BURN treatments, respectively. After treatment, juniper presence from untreated small trees (<1 m tall; PILE and CUT treatments) and seedling emergence (all treatments) represented 25–33 % of pre-treatment tree density. To maintain recovery of herbaceous, shrub, and mahogany species additional control of reestablished juniper will be necessary.