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Background: In open abdominal surgery, continuous epidural analgesia is commonly used method for postoperative analgesia. However, ultrasound (US)-guided fascial plane blocks may be a reasonable alternative. Methods: In this randomized controlled trial, we compared posterior quadratus lumborum block (QLB) with epidural analgesia for postoperative pain after open radical cystectomy (ORC). Adult patients aged 18–85 with bladder cancer (BC) scheduled for open RC were randomized in two groups. Exclusion criteria were complicated diabetes mellitus type I, lack of cooperation, and persistent pain for reasons other than BC. In one group, a bilateral US-guided single injection posterior QLB was performed with 3.75 mg/ml ropivacaine 20 ml/side. In the other group, continuous epidural analgesia with ropivacaine was used. Basic analgesia was oral paracetamol 1000 mg three times daily, and long-acting opioid twice daily in both groups. All patients had patient-controlled rescue analgesia with oxycodone. Postoperative cumulative rescue opioid consumption was recorded for the day of surgery, and the following 2 postoperative days (POD 0–2). Secondary outcomes were postoperative pain and nausea and vomiting. Results: In total, 20 patients (QLB), and 19 patients (epidural analgesia) groups, were included in the analyses. Cumulative rescue opioid consumption on POD 0, being of duration 9–12 h, was 14 mg (7.6–33.3) in the QLB group versus 6.1 mg (2.0–16.1) in the epidural analgesia group, p = 0.089, and as doses, 8 doses (3.6–15.7) versus 4 doses (1.3–8.5), p =.057. On POD 1 consumption was 25.3 mg (11.0–52.9) versus 18.0 mg (14.4–43.7), p =.749, and as doses 12 (5.5–23.0) versus 10 (8–20), p >.9, respectively. On POD 2 consumption was 19.1 mg (7.9–31.0) versus 18.0 mg (5.4–27.6) p =.749, and as doses 8.5 (5.2–14.7) versus 11 (3.0–18.0) p >.9, respectively. Conclusion: Opioid consumption did not differ significantly between posterior QLB and an epidural infusion with ropivacaine for the first 2 postoperative days following RC. Trial registration: ClinicalTrials.gov identifier NCT03328988. publishedVersion

12 páginas.- 4 figuras.- referencias.- Additional supporting information can be found online in the Supporting Information section at the end of this article.- Full Access in https://onlinelibrary.wiley.com/doi/full/10.1111/geb.13652, Aim Our understanding of the mechanisms that maintain forest diversity under changing climate can benefit from knowledge about traits that are closely linked to fitness. We tested whether the link between traits and seed number and seed size is consistent with two hypotheses, termed the leaf economics spectrum and the plant size syndrome, or whether reproduction represents an independent dimension related to a seed size–seed number trade-off. Location Most of the data come from Europe, North and Central America and East Asia. A minority of the data come from South America, Africa and Australia. Time period 1960–2022. Major taxa studied Trees. Methods We gathered 12 million observations of the number of seeds produced in 784 tree species. We estimated the number of seeds produced by individual trees and scaled it up to the species level. Next, we used principal components analysis and generalized joint attribute modelling (GJAM) to map seed number and size on the tree traits spectrum. Results Incorporating seed size and number into trait analysis while controlling for environment and phylogeny with GJAM exposes relationships in trees that might otherwise remain hidden. Production of the large total biomass of seeds [product of seed number and seed size; hereafter, species seed productivity (SSP)] is associated with high leaf area, low foliar nitrogen, low specific leaf area (SLA) and dense wood. Production of high seed numbers is associated with small seeds produced by nutrient-demanding species with softwood, small leaves and high SLA. Trait covariation is consistent with opposing strategies: one fast-growing, early successional, with high dispersal, and the other slow-growing, stress-tolerant, that recruit in shaded conditions. Main conclusions Earth system models currently assume that reproductive allocation is indifferent among plant functional types. Easily measurable seed size is a strong predictor of the seed number and species seed productivity. The connection of SSP with the functional traits can form the first basis of improved fecundity prediction across global forests., The project has been funded by grants to J.S.C. from the National Science Foundation, most re-cently DEB-1754443, and by the Belmont Forum (1854976), NASA (AIST16-0052 and AIST18-0063) and the Programme d'Investissement d'Avenir under project FORBIC (18-MPGA-0004; Make Our Planet Great Again). Jerry Franklin's data remain acces-sible through NSF LTER DEB-1440409. Data from Hubbard Brook (New Hampshire) were funded through NSF-LTER. Puerto Rico data were funded by NSF grants, most recently DEB 0963447 and LTREB 11222325. Data from the Andes Biodiversity and Ecosystem Research Group were funded by the Gordon and Betty Moore Foundation and NSF 727 LTREB 1754647. M.B. was supported by grant no. 2019/35/D/NZ8/00050 from the (Polish) National Science Centre and by Polish National Agency for Academic Exchange Bekker programme PPN/BEK/2020/1/00009/U/00001. Research by the USDA Forest Service and the USGS was funded by these agencies. Any use of trade, firm or product names does not imply endorsement by the US Government. Any use of trade, firm, or product names is for descriptive purposes only and does not imply en -dorsement by the U.S. Government

Background Hepatocellular carcinoma (HCC) patient‐derived xenograft (PDX) models hold potential to advance knowledge in HCC biology to help improve systemic therapies. Beside hepatitis B virus‐associated tumors, HCC is poorly established in PDX. Methods PDX formation from fresh HCC biopsies were obtained and implanted intrahepatically or in subrenal capsule (SRC). Mouse liver injury was induced in immunodeficient Fah−/− mice through cycling off nitisinone after HCC biopsy implantation, versus continuous nitisinone as non‐liver injury controls. Mice with macroscopically detectable PDX showed rising human alpha1‐antitrypsin (hAAT) serum levels, and conversely, no PDX was observed in mice with undetectable hAAT. Results Using rising hAAT as a marker for PDX formation, 20 PDX were established out of 45 HCC biopsy specimens (44%) reflecting the four major HCC etiologies most commonly identified at Memorial SloanKettering similar to many other institutions in the United States. PDX was established only in severely immunodeficient mice lacking lymphocytes and NK cells. Implantation under the renal capsule improved PDX formation two‐fold compared to intrahepatic implantation. Two out of 18 biopsies required murine liver injury to establish PDX, one associated with hepatitis C virus and one with alcoholic liver disease. PDX tumors were histologically comparable to biopsy specimens and 75% of PDX lines could be passaged. Conclusions Using cycling off nitisinone‐induced liver injury, HCC biopsies implanted under the renal capsule of severely immunodeficient mice formed PDX with 57% efficiency as determined by rising hAAT levels. These findings facilitate a more efficient make‐up of PDX for research into subset‐specific HCC.

Rhetorical discourse analysis (RDA) brings together methods and theories from strands of discourse analysis (DA), classical rhetoric, and rhetorical analysis. Keywords: discourse analysis; rhetoric; forensic linguistics

Novel anticancer compounds and their precision delivery systems are actively developed to create potent and well‐tolerated anticancer therapeutics. Here, we report the synthesis of a novel anthracycline, Utorubicin (UTO), and its preclinical development as an anticancer payload for nanocarriers. Free UTO was significantly more toxic to cultured tumor cell lines than the clinically used anthracycline, doxorubicin. Nanoformulated UTO, encapsulated in polymeric nanovesicles (polymersomes, PS), reduced the viability of cultured malignant cells and this effect was potentiated by functionalization with a tumor‐penetrating peptide (TPP). Systemic peptide‐guided PS showed preferential accumulation in triple‐negative breast tumor xenografts implanted in mice. At the same systemic UTO dose, the highest UTO accumulation in tumor tissue was seen for the TPP‐targeted PS, followed by nontargeted PS, and free doxorubicin. Our study suggests potential applications for UTO in the treatment of malignant diseases and encourages further preclinical and clinical studies on UTO as a nanocarrier payload for precision cancer therapy., Utorubicin (UTO) is a novel anthracycline with higher anticancer activity than doxorubicin in cultured cancer cells. Nanoencapsulation of UTO in polymeric vesicles functionalized with tumor‐penetrating peptides increases the cytotoxicity of the drug in receptor‐positive cells in vitro and, after systemic administration into mice bearing triple‐negative tumors, potentiates UTO accumulation in malignant tissue.

Ongoing changes in fire regimes have the potential to drive widespread shifts in Earth's vegetation. Plant traits and vital rates provide insight into vulnerability to fire‐driven vegetation shifts because they can be indicators of the ability of individuals to survive fire (resistance) and populations to persist (resilience) following fire. In 15 study sites spanning climatic gradients in the southern Rocky Mountains, USA, we quantified variation in key traits and vital rates of two co‐occurring, widely distributed conifers (Pinus ponderosa Douglas ex. P. Lawson & C. Lawson and Pseudotsuga menziesii (Mirb.) Franco). We used mixed‐effects models to explain inter‐ and intraspecific variation in tree growth, survival, bark thickness and seed cone production, as a function of species, tree life stage (i.e. diameter, height and age), average climate, local competition and site conditions. Pinus ponderosa was predicted to survive low‐severity fire at a 23% earlier age than P. menziesii. Pinus ponderosa had thicker bark and more rapid juvenile height growth, traits conferring greater fire resistance. In contrast, P. menziesii was predicted to produce seed cones at a 28% earlier age than P. ponderosa. For both species, larger individuals were more likely to survive fire and to produce cones. For P. ponderosa, cone production increased where average actual evapotranspiration (AET) was higher and local competition was lower. More frequent cone production on productive sites with higher AET is an important and underappreciated mechanism that may help to explain greater resilience to fire in these areas. Synthesis. Our analyses indicated that many plant traits and vital rates related to fire differed between Pinus ponderosa and Pseudotsuga menziesii, with trade‐offs between investment in traits that promote individual defence to fire and those that promote recolonization of disturbed sites. Future changes in fire regimes will act as a filter throughout North American forests, with our findings helping to infer which individuals and populations of two iconic species are most vulnerable to future change and offering a framework for future inquiry in other forests facing an uncertain future.

Research Summary Why do top executives leave their firms? Research on executive turnover has either focused on CEO dismissal or on group‐level top management team (TMT) departure rates, mostly ignoring individual‐level factors that would predict why non‐CEO executives exit. Here, we extend the shock perspective of the unfolding model of turnover used in organizational behavior research to show how relational and reputational shocks influence turnover at the executive level. Our sample includes over 4,000 executives from S&P 1500 firms over 11 years. We hypothesize and find that relational and reputational shocks increase the likelihood of top executive exit. We also consider the moderating influence of pay disparity on these relationships, which impacts how each type of shock influences executive turnover. Managerial Summary Replacing top executives can be extremely costly for firms. Consequently, understanding the reasons behind top executive exit are important. We examine the effect of different types of shock on the likelihood a top executive will exit their firm. We find that both relational shocks (e.g., other members of the TMT leaving), as well as reputational shocks (e.g., litigation or shareholder activism against the firm), increase turnover. However, we find that higher status executives experience these shocks differently than lower status executives.

The coronavirus disease‐2019 (COVID‐19) is a viral illness with heterogenous clinical manifestations, ranging from mild symptoms to severe acute respiratory distress syndrome and shock caused by the severe acute respiratory syndrome coronavirus‐2. The global healthcare community is rapidly learning more about the effects of COVID‐19 on the cardiovascular system, as well as the strategies for management of infected patients with cardiovascular disease. There is minimal literature available surrounding the relationship between COVID‐19 infection and acute coronary syndrome. We describe the case of a woman who presented with an acute anterior ST‐elevation myocardial infarction managed by primary percutaneous coronary intervention, who subsequently developed severe COVID‐19 infection and ultimately succumbed to multisystem organ failure.

Understanding potential limitations to tree regeneration is essential as rates of tree mortality increase in response to direct (extreme drought) and indirect (bark beetle outbreaks, wildfire) effects of a warming climate. Seed availability is increasingly recognized as an important limitation for tree regeneration. High variability in seed cone production is a trait common among many northern temperate conifers, but few studies examine the determinants of individual tree cone production and how they vary with stand structure. In subalpine forests in the southern Rocky Mountains, USA, we monitored >1600 Picea engelmannii (Engelmann spruce) and Abies lasiocarpa (subalpine fir) trees for cone presence (an indicator of reproductive maturity) and a subset of those trees for cone abundance (an indicator of seed production) from 2016 to 2018. We constructed mixed models to test how individual tree cone presence and cone abundance were affected by tree size and age as well as forest attributes at the neighborhood‐ and stand‐scales. The probability of cone presence and cone abundance increased with tree size and age for A. lasiocarpa and P. engelmannii. The youngest ages of trees with cones present were more than 100 yr later for individuals in high basal area (BA) stands (>65 m2/ha) relative to low BA stands (

Understanding how severe disturbances and their interactions affect forests is key to projecting ecological change under a warming climate. Substantial increases in some biotic disturbances, such as bark beetle outbreaks, in temperate forest ecosystemsmay compromise recovery to a forest vegetation type (i.e., physiognomic recovery or resilience), especially if subsequent biotic disturbances (e.g., herbivory) alter recovery mechanisms. From 2005 to 2017, severe outbreaks (>90% mortality) of spruce bark beetles (SB, Dendroctonus rufipennis) affected Engelmann spruce (Picea engelmannii) across 325,000 ha of spruce and subalpine fir (Abies lasiocarpa) forest in the southern Rocky Mountains, USA. Concurrently, an outbreak of western balsam bark beetle (WBBB, Dryocoetes confuses) infested subalpine fir across at least 47,000 of these hectares. We explored the capacity of 105 stands affected by one or two bark beetle outbreaks and browsing of juvenile trees by ungulates to return to a forest vegetation type in the context of pre-outbreak forest conditions and topography. Nine initial forest trajectories (i.e., at least several decades) were identified from four pre-outbreak forest types affected by three biotic disturbances that occurred at different spatial scales and severities. Most stands (86%) contained surviving nonhost adult trees in the main canopy (fir and aspen [Populus tremuloides]) and many surviving juveniles of all species, implying that they are currently on a trajectory for physiognomic recovery. Stands composed exclusively of large-diameter spruce were affected by a severe SB outbreak and were most vulnerable to a transition to a low-density forest, below regional stocking levels (

In the absence of broad-scale disturbance, many temperate coniferous forests experience successful seedling establishment only when abundant seed production coincides with favorable climate. Identifying the frequency of past establishment events and the climate conditions favorable for seedling establishment is essential to understanding how climate warming could affect the frequency of future tree establishment events and therefore future forest composition or even persistence of a forest cover. In the southern Rocky Mountains, USA, research on the sensitivity of establishment of Engelmann spruce (Picea engelmannii) and subalpine fir (Abies lasiocarpa)-two widely distributed, co-occurring conifers in North America-to climate variability has focused on the alpine treeline ecotone, leaving uncertainty about the sensitivity of these species across much of their elevation distribution. We compared annual germination dates for >450 Engelmann spruce and >500 subalpine fir seedlings collected across a complex topographic-moisture gradient to climate variability in the Colorado Front Range. We found that Engelmann spruce and subalpine fir established episodically with strong synchrony in establishment events across the study area. Broad-scale establishment events occurred in years of high soil moisture availability, which were characterized by above-average snowpack and/or cool and wet summer climatic conditions. In the recent half of the study period (1975-2010), a decrease in the number of fir and spruce establishment events across their distribution coincided with declining snowpack and a multi-decadal trend of rising summer temperature and increasing moisture deficits. Counter to expected and observed increases in tree establishment with climate warming in maritime subalpine forests, our results show that recruitment declines will likely occur across the core of moisture-limited subalpine tree ranges as warming drives increased moisture deficits.