The Urban Heat Island Effect (UHIE) is a widely recognised phenomenon that profoundly affects the quality of life for urban citizens. Urban greenspace can help mitigate the UHIE, but the ...characteristics that determine the extent to which any given greenspace can cool an urban area are not well understood. A key characteristic is likely to be the properties of trees that are found in a greenspace. Here, we explore the sensitivity of the strength of the cooling effect to tree community structure for greenspaces in Changzhou, China. Land surface temperatures were retrieved from Landsat 7 ETM+ and Landsat 8 TIRS and were used to evaluate the temperature drop amplitude (TDA) and cooling range (CR) of 15 greenspaces across each of the four seasons. Tree community structure of the greenspaces was investigated using 156 sample plots across the 15 greenspaces. We found that a number of plant community structure indicators of greenspaces have a significant impact on the strength of the cooling effect. The Shannon-Wiener diversity index, tree species richness and tree canopy coverage of greenspaces are all positively correlated with the magnitude of the temperature drop amplitude, with the strength of their influence varying seasonally. We also find that mean crown width is positively correlated with cooling range in summer and autumn, while greenspace tree density is negatively correlated with cooling range in winter. Our findings improve understanding of the relationship between plant community structure and the cooling effect of greenspaces. In particular, we highlight the important role that tree species diversity provides for mitigating the UHIE, and suggest that if planners wish to improve the role of urban greenspaces in cooling cities, they should include a higher diversity of trees species.
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•Cooling effect of greenspaces varies seasonally•Tree diversity and tree coverage positively correlated with temperature drop amplitude•Tree crown width positively correlated with cooling range, and tree density negatively correlated with the cooling range.•Optimizing the plant community structure improves the cooling effect of greenspaces without increasing their size.
The commensal gut microbiota has been implicated as a determinant in several human diseases and conditions. There is mounting evidence that the gut microbiota of laboratory mice (Mus musculus) ...similarly modulates the phenotype of mouse models used to study human disease and development. While differing model phenotypes have been reported using mice purchased from different vendors, the composition and uniformity of the fecal microbiota in mice of various genetic backgrounds from different vendors is unclear. Using culture-independent methods and robust statistical analysis, we demonstrate significant differences in the richness and diversity of fecal microbial populations in mice purchased from two large commercial vendors. Moreover, the abundance of many operational taxonomic units, often identified to the species level, as well as several higher taxa, differed in vendor- and strain-dependent manners. Such differences were evident in the fecal microbiota of weanling mice and persisted throughout the study, to twenty-four weeks of age. These data provide the first in-depth analysis of the developmental trajectory of the fecal microbiota in mice from different vendors, and a starting point from which researchers may be able to refine animal models affected by differences in the gut microbiota and thus possibly reduce the number of animals required to perform studies with sufficient statistical power.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background and Aims
Lenvatinib is an effective drug in advanced HCC. Its combination with the anti‐PD1 (programmed cell death protein 1) immune checkpoint inhibitor, pembrolizumab, has generated ...encouraging results in phase Ib and is currently being tested in phase III trials. Here, we aimed to explore the molecular and immunomodulatory effects of lenvatinib alone or in combination with anti‐PD1.
Approach and Results
We generated three syngeneic models of HCC in C57BL/6J mice (subcutaneous and orthotopic) and randomized animals to receive placebo, lenvatinib, anti‐PD1, or combination treatment. Flow cytometry, transcriptomic, and immunohistochemistry analyses were performed in tumor and blood samples. A gene signature, capturing molecular features associated with the combination therapy, was used to identify a subset of candidates in a cohort of 228 HCC patients who might respond beyond what is expected for monotherapies. In mice, the combination treatment resulted in tumor regression and shorter time to response compared to monotherapies (P < 0.001). Single‐agent anti‐PD1 induced dendritic and T‐cell infiltrates, and lenvatinib reduced the regulatory T cell (Treg) proportion. However, only the combination treatment significantly inhibited immune suppressive signaling, which was associated with the TGFß pathway and induced an immune‐active microenvironment (P < 0.05 vs. other therapies). Based on immune‐related genomic profiles in human HCC, 22% of patients were identified as potential responders beyond single‐agent therapies, with tumors characterized by Treg cell infiltrates, low inflammatory signaling, and VEGFR pathway activation.
Conclusions
Lenvatinib plus anti‐PD1 exerted unique immunomodulatory effects through activation of immune pathways, reduction of Treg cell infiltrate, and inhibition of TGFß signaling. A gene signature enabled the identification of ~20% of human HCCs that, although nonresponding to single agents, could benefit from the proposed combination.
Atmospheric new-particle formation affects climate and is one of the least understood atmospheric aerosol processes. The complexity and variability of the atmosphere has hindered elucidation of the ...fundamental mechanism of new-particle formation from gaseous precursors. We show, in experiments performed with the CLOUD (Cosmics Leaving Outdoor Droplets) chamber at CERN, that sulfuric acid and oxidized organic vapors at atmospheric concentrations reproduce particle nucleation rates observed in the lower atmosphere. The experiments reveal a nucleation mechanism involving the formation of clusters containing sulfuric acid and oxidized organic molecules from the very first step. Inclusion of this mechanism in a global aerosol model yields a photochemically and biologically driven seasonal cycle of particle concentrations in the continental boundary layer, in good agreement with observations.
Vegetation fires emit large quantities of aerosol into the
atmosphere, impacting regional air quality and climate. Previous work has
used comparisons of simulated and observed aerosol optical depth ...(AOD) in
regions heavily impacted by fires to suggest that emissions of aerosol particles
from fires may be underestimated by a factor of 2–5. Here we use surface,
aircraft and satellite observations made over the Amazon during September
2012, along with a global aerosol model to improve understanding of aerosol
emissions from vegetation fires. We apply three different satellite-derived
fire emission datasets (FINN, GFED, GFAS) in the model. Daily mean aerosol
emissions in these datasets vary by up to a factor of 3.7 over the Amazon
during this period, highlighting the considerable uncertainty in emissions.
We find variable agreement between the model and observed aerosol mass
concentrations. The model reproduces observed aerosol concentrations
over deforestation fires well in the western Amazon during dry season conditions
with FINN or GFED emissions and during dry–wet transition season conditions
with GFAS emissions. In contrast, the model underestimates aerosol
concentrations over savanna fires in the Cerrado environment east of the
Amazon Basin with all three fire emission datasets. The model generally
underestimates AOD compared to satellite and ground stations, even when the
model reproduces the observed vertical profile of aerosol mass
concentration. We suggest it is likely caused by uncertainties in the
calculation of AOD, which are as large as ∼90 %, with the
largest sensitivities due to uncertainties in water uptake and relative
humidity. Overall, we do not find evidence that particulate emissions from
fires are systematically underestimated in the Amazon region and we caution
against using comparison with AOD to constrain particulate emissions from
fires.
Purpose
The effect of advanced age per se versus severity of chronic and acute diseases on the short- and long-term survival of older patients admitted to the intensive care unit (ICU) remains ...unclear.
Methods
Intensive care unit admissions to the surgical ICU and medical ICU of patients older than 65 years were analyzed. Patients were divided into three age groups: 65–74, 75–84, and 85 and above. The primary endpoints were 28-day and 1-year mortality.
Results
The analysis focused on 7,265 patients above the age of 65, representing 45.7 % of the total ICU population. From the first to third age group there was increased prevalence of heart failure (25.9–40.3 %), cardiac arrhythmia (24.6–43.5 %), and valvular heart disease (7.5–15.8 %). There was reduced prevalence of diabetes complications (7.5–2.4 %), alcohol abuse (4.1–0.6 %), chronic obstructive pulmonary disease (COPD) (24.4–17.4 %), and liver failure (5.0–1.0 %). Logistic regression analysis adjusted for gender, sequential organ failure assessment, do not resuscitate, and Elixhauser score found that patients from the second and third age group had odds ratios of 1.38 95 % confidence interval (CI) 1.19–1.59 and 1.53 (95 % CI 1.29–1.81) for 28-day mortality as compared with the first age group. Cox regression analysis for 1-year mortality in all populations and in 28-day survivors showed the same trend.
Conclusions
The proportion of elderly patients from the total ICU population is high. With advancing age, the proportion of various preexisting comorbidities and the primary reason for ICU admission change. Advanced age should be regarded as a significant independent risk factor for mortality, especially for ICU patients older than 75.
Interleukin (IL)-33 is a broad-acting alarmin cytokine that can drive inflammatory responses following tissue damage or infection and is a promising target for treatment of inflammatory disease. ...Here, we describe the identification of tozorakimab (MEDI3506), a potent, human anti-IL-33 monoclonal antibody, which can inhibit reduced IL-33 (IL-33
) and oxidized IL-33 (IL-33
) activities through distinct serum-stimulated 2 (ST2) and receptor for advanced glycation end products/epidermal growth factor receptor (RAGE/EGFR complex) signalling pathways. We hypothesized that a therapeutic antibody would require an affinity higher than that of ST2 for IL-33, with an association rate greater than 10
M
s
, to effectively neutralize IL-33 following rapid release from damaged tissue. An innovative antibody generation campaign identified tozorakimab, an antibody with a femtomolar affinity for IL-33
and a fast association rate (8.5 × 10
M
s
), which was comparable to soluble ST2. Tozorakimab potently inhibited ST2-dependent inflammatory responses driven by IL-33 in primary human cells and in a murine model of lung epithelial injury. Additionally, tozorakimab prevented the oxidation of IL-33 and its activity via the RAGE/EGFR signalling pathway, thus increasing in vitro epithelial cell migration and repair. Tozorakimab is a novel therapeutic agent with a dual mechanism of action that blocks IL-33
and IL-33
signalling, offering potential to reduce inflammation and epithelial dysfunction in human disease.
Increased demand for self-managed medication abortion in states with in-clinic restrictions or high infection rates during the coronavirus disease 2019 (COVID-19) pandemic demonstrates the need for ...remote abortion care models.
Biogenic volatile organic compounds (BVOCs) affect climate via changes to aerosols, aerosol-cloud interactions (ACI), ozone and methane. BVOCs exhibit dependence on climate (causing a feedback) and ...land use but there remains uncertainty in their net climatic impact. One factor is the description of BVOC chemistry. Here, using the earth-system model UKESM1, we quantify chemistry's influence by comparing the response to doubling BVOC emissions in the pre-industrial with standard and state-of-science chemistry. The net forcing (feedback) is positive: ozone and methane increases and ACI changes outweigh enhanced aerosol scattering. Contrary to prior studies, the ACI response is driven by cloud droplet number concentration (CDNC) reductions from suppression of gas-phase SO
oxidation. With state-of-science chemistry the feedback is 43% smaller as lower oxidant depletion yields smaller methane increases and CDNC decreases. This illustrates chemistry's significant influence on BVOC's climatic impact and the more complex pathways by which BVOCs influence climate than currently recognised.
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