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Abstract Background Poly-victimization (PV) not only threatens physical and mental health but also causes a range of social problems. Left-behind children in rural areas are more likely to experience PV problems. However, there have been fewer studies on PV among rural children, and even fewer intervention studies. Objective The difference-in-differences method was employed to analyze the impact of intervention measures, based on the theory of planned behavior, on PV among left-behind children in rural areas. Methods The study subjects were left-behind children from six middle schools in two cities in southern China, who completed the baseline survey from 2020 to 2021. They were divided into a control group and an intervention group, each consisting of 228 cases, based on their schools. Before and after the intervention, the Self-made victimization-related knowledge, attitude, and practice questionnaire, Poly-victimization scale, and Middle school students’ coping style scale were used to evaluate the victimization-related KAP(knowledge, attitude, and practice), victimization occurrence, and coping styles of left-behind children, respectively. Stata 15.0 was used to establish a difference-in-differences regression model to analyze the impact of the intervention measures on poly-victimization and coping styles. Results Mixed Anova revealed that after the intervention, the KAP scores of the intervention group were significantly higher than those of the control group (p

Abstract To effectively control the dust generated by coal mining operations, a new type of cyclonic pneumatic mist curtain dust control device was developed. Using CFD software, numerical simulations were conducted on the internal airflow velocity field, the exit velocity of the cyclonic pneumatic mist curtain, and the mist droplet particle field of the curtain. Experiments were carried out to measure the spray coverage, droplet size, and the dust control performance of the model device. The results indicate that when the water pump supply pressure is 8 MPa, the fan supply wind speed is 12 m/s, and the nozzle installation angle is 75 degrees, the cyclonic pneumatic mist curtain dust control device model operates under optimal conditions. The effective coverage of the cyclonic mist curtain is 380 × 3300 mm, fully suppressing dust generation on one side of the curtain. An optimal dust removal distance of about 90 cm was determined. After installing the cyclonic pneumatic mist curtain dust control device, the average dust reduction efficiency for respirable dust reached 91.07%, and the overall dust reduction efficiency achieved 93.34%.

Abstract Introduction Sepsis is a severe disease with a complex pathogenesis and is an important factor in the mortality of patients in intensive care units (ICUs). The administration of vitamin C and its combination treatment in sepsis was not supported by the results of multiple randomized controlled clinical trials. However, the efficacy of a higher vitamin C dose in treating patients with sepsis remains unclear. Therefore, the effectiveness of administering a larger dosage of vitamin C to patients with sepsis remains unclear. Methods and Analysis The Clinical Efficacy of Megadose Vitamin C in Sepsis (CEMVIS) trial is a multicenter, single-blind, randomized, placebo-controlled trial with 234 individuals with sepsis. The following adult patients will be enrolled: those with procalcitonin (PCT) ≥ 2 ng/mL and sepsis 3.0 diagnostic criteria. Patients will be randomly assigned to receive 12 g vitamin C or the same volume of 5% glucose injection intravenously pumped every 12 h for 4 days or up to the moment they are discharged from ICU. The primary outcome will be the mortality within 28 days. Secondary outcomes will mainly include protection and support of organ functions, improvement in inflammatory status, and length of ICU stay. Moreover, adverse events and serious adverse events will be meticulously recorded. Ethics This study was approved by the Clinical Ethics Committee of Zhujiang Hospital of Southern Medical University (2020-KY-069-05). The trial results will be published in peer-reviewed journals or at national or international conferences. Trial registration clinicaltrials.gov, NCT05194189, Registered 3 January 2022, URL: https://www.clinicaltrials.gov .

BackgroundThere is accumulating evidence regarding the benefits of the 5-HT3 receptor antagonist ondansetron for the treatment of critical illness due to its potential anti-inflammatory effect. This study attempted to determine the potential targets and molecular mechanisms of ondansetron’s action against critical illnesses.MethodsA bioinformatics analysis of network pharmacology was conducted to demonstrate screening targets and the signaling pathways of ondansetron action against the most common critical illnesses such as acute kidney injury (AKI), sepsis, and acute respiratory distress syndrome (ARDS). Experiments of LPS-stimulated rat neutrophils with ondansetron treatment were conducted to further validate the relevant hypothesis.ResultsA total of 198, 111, and 26 primary causal targets were identified from the data for the action of ondansetron against AKI, sepsis, and ARDS respectively. We found that the pathway of neutrophil extracellular traps (NETs) formation is statistically significantly involved in the action of ondansetron against these three critical illnesses. In the pathway of NETs formation, the common drug-disease intersection targets in these three critical illnesses were toll-like receptor 8 (TLR8), mitogen-activated protein kinase-14 (MAPK14), nuclear factor kappa-B1 (NFKB1), neutrophil elastase (NE), and myeloperoxidase (MPO). Considering these bioinformatics findings, we concluded that ondansetron anti-critical illness effects are mechanistically and pharmacologically implicated with suppression of neutrophils-associated inflammatory processes. It was also showed that after treatment of LPS-stimulated rat neutrophils with ondansetron, the key proteins NE, MPO, and Peptide Arginine Deaminase 4 (PAD4) in the NETs formation were significantly reduced, and the inflammatory factors IL-6, IL-1β, TNF-α, and chemokine receptor (CXCR4) were also significantly decreased.ConclusionThe excessive formation of NETs may have important research value in the development and progression of critical illness. Ondansetron may reduce excessive inflammatory injury in critical diseases by reducing the formation of NETs via influencing the five targets: TLR8, NFKB1, MAPK14, NE, and MPO. Ondansetron and these primary predictive biotargets may potentially be used to treat critical illness in future clinical practice.

Abstract Although the 2021 Western North America (WNA) heat wave was predicted by weather forecast models, questions remain about whether such strong events can be simulated by global climate models (GCMs) at different model resolutions. Here, we analyze sets of GCM simulations including historical and future periods to check for the occurrence of similar events. High‐ and low‐resolution simulations both encounter challenges in reproducing events as extreme as the observed one, particularly under the present climate. Relatively stronger amplitudes are observed during the future periods. Furthermore, high‐ and low‐resolution short initialized GCM simulations are both able to reasonably predict such strong events and their associated high‐pressure ridge over the WNA with a 1 week forecast lead time. Moisture sensitivity experiments further indicate a drier atmospheric moisture condition results in substantially higher near‐surface temperatures in the simulated heat events.

The compression of coral concrete-filled aluminum alloy tube columns is a novel type of laterally restrained concrete element, with axial compressive load being the primary load type sustained by the laterally restrained concrete elements during their service life. In this study, square intermediate-length columns of coral concrete-filled aluminum alloy tubes were subjected to axial compression tests to investigate the influence of section width-to-thickness ratio (B/t), and aspect ratio of the column (L/B) on the failure mode, ultimate load-carrying capacity, and load-deformation relationship of the specimens. The research findings demonstrate that the intermediate-length columns of coral concrete-filled aluminum alloy tube exhibit good compressive performance, with a significant combined effect between the aluminum alloy tube and the core concrete. With an increase in the section width-to-thickness ratio (B/t), the compressive stiffness, ultimate load-carrying capacity, and deformation ductility of the specimens all decrease. As the aspect ratio of the column (L/B) increases, under the condition that end-zone failure does not occur, the ultimate load-carrying capacity and deformation ductility of the specimens gradually decrease, while the extent of flexural deformation significantly increases.

Abstract We investigate the role of ocean heat transport (OHT) in driving the decadal variability of the Arctic climate by analyzing the pre‐industrial control simulation of a high‐resolution climate model. While the OHT variability at 65°N is greater in the Atlantic, we find that the decadal variability of Arctic‐wide surface temperature and sea ice area is much better correlated with Bering Strait OHT than Atlantic OHT. In particular, decadal Bering Strait OHT variability causes significant changes in local sea ice cover and air‐sea heat fluxes, which are amplified by shortwave feedbacks. These heat flux anomalies are regionally balanced by longwave radiation at the top of the atmosphere, without compensation by atmospheric heat transport (Bjerknes compensation). The sensitivity of the Arctic to changes in OHT may thus rely on an accurate representation of the heat transport through the Bering Strait, which is difficult to resolve in coarse‐resolution ocean models.

Abstract Biweekly sea surface temperature (SST) variability significantly contributes to over 50% of the intraseasonal variability in the eastern equatorial Pacific (EEP) and Atlantic (EEA). Our study investigates this biweekly variability, employing a blend of in–situ and reanalysis data sets. The research identifies biweekly signals in SST, meridional wind, and ocean currents, notably in September–November in EEP and June–August in EEA. Biweekly southerly (northerly) winds drive instantaneous northward (southward) ocean currents in EEP, but with a 1–2‐day phase delay in EEA. Consequently, these currents lead to SST anomalies with a 3–4‐day lag in both EEP and EEA due to the presence of the cold tongue. The study reveals the origin of biweekly wind fluctuations in the western Pacific for EEP and the subpolar Pacific for EEA, connected by atmospheric Rossby waves validated through a linearized non‐divergent barotropic model. This research affirms the influence of subtropical and subpolar atmospheric forcing on equatorial SST.

Tropical cyclone (TC) projections with atmosphere-only models are associated with uncertainties due to their inability to represent TC-ocean interactions. However, global coupled models, which represent TC-ocean interactions, can produce basin-scale sea surface temperature biases in seasonal to centennial simulations that lead to challenges in representing TC activity. Therefore, focusing on recent individual major hurricane events, we investigated the influence of TC-ocean coupling on the response of TCs to anthropogenic change using atmosphere-only and coupled atmosphere-ocean regional model simulations. Under an extremely warm scenario, coupling does not influence the signs of projected TC rainfall and intensity responses. Coupling, however, does influence the magnitude of projected intensity and especially rainfall. Within a 500 km radius region of the TCs, the projected rainfall increases in coupled simulations are 3–59 % less than in the atmosphere-only simulations, driven by enhanced TC-induced sea surface temperature cooling in the former. However, the influence of coupling on the magnitude of projected rainfall could vary considerably over the regions of highest rainfall generated by TCs.

The reliability of energy systems is strongly influenced by the prevailing climate conditions. With the increasing prevalence of renewable energy sources, the interdependence between energy and climate systems has become even stronger. This study examines the impact of different spatial resolutions in climate modeling on energy grid reliability assessment, with the Texas interconnection between 2033 and 2043 serving as a pilot case study. Our preliminary findings indicate that while low-resolution climate simulations can provide a rough estimate of system reliability, high-resolution simulations can provide more informative assessment of low-adequacy extreme events. Furthermore, both high- and low-resolution assessments suggest the need to prepare for severe blackout events in winter due to extremely low temperatures.

Abstract Background The ossification mechanism of the temporomandibular joint (TMJ) condyle remains unclear in human embryo. The size and structure of TMJ, shape of articular disc and the characteristics of omnivorous chewing in the pig are similar to those of humans. The pig is an ideal animal for studying the mechanism of ossification of the TMJ condyle during the embryonic period. Method In a previous study by our group, it was found that there was no condylar ossification on embryonic day(E) 45, but the ossification of condyle occurred between E75 and E90. In this study, a total of 12 miniature pig embryos on E45 and E85 were used. Six embryos were used for tissue sections (3 in each group). The remaining six embryos were used for transcriptomic and proteomic studies to find differential genes and proteins. The differentially expressed genes in transcriptome and proteomic analysis were verified by QPCR. Results In total, 1592 differential genes comprising 1086 up‐regulated genes and 506 down‐regulated genes were screened for fold changes of ≥2 to ≤0.5 between E45 and E85. In the total of 4613 proteins detected by proteomic analysis, there were 419 differential proteins including 313 up‐regulated proteins and 106 down‐regulated proteins screened for fold changes of ≥2 to ≤0.5 between E45 and E85. A total of 36 differential genes differing in both transcriptome and proteome analysis were found. QPCR analysis showed that 14 of 15 selected genes were consistent with transcriptome analysis. Conclusion Condylar transcriptome and proteomic analysis during the development of TMJ in miniature pigs revealed the regulatory genes/proteins of condylar ossification.

Abstract The Kuroshio Extension (KE) has far-reaching influences on climate as well as on local marine ecosystems. Thus, skillful multi-year to decadal prediction of the KE state and understanding sources of skill are valuable. Retrospective forecasts using the high-resolution Community Earth System Model (CESM) show exceptional skill in predicting KE variability up to lead year 4, substantially higher than the skill found in a similarly configured low-resolution CESM. The higher skill is attained because the high-resolution system can more realistically simulate the westward Rossby wave propagation of initialized ocean anomalies in the central North Pacific and their expression within the sharp KE front, and does not suffer from spurious variability near Japan present in the low-resolution CESM that interferes with the incoming wave propagation. These results argue for the use of high-resolution models for future studies that aim to predict changes in western boundary current systems and associated biological fields.

Abstract The impact of increased model horizontal resolution on climate prediction performance is examined by comparing results from low-resolution (LR) and high-resolution (HR) decadal prediction simulations conducted with the Community Earth System Model (CESM). There is general improvement in global skill and signal-to-noise characteristics, with particularly noteworthy improvements in the eastern tropical Pacific, when resolution is increased from order 1° in all components to order 0.1°/0.25° in the ocean/atmosphere. A key advance in the ocean eddy-resolving HR system is the reduction of unrealistic warming in the Southern Ocean (SO) which we hypothesize has global ramifications through its impacts on tropical Pacific multidecadal variability. The results suggest that accurate representation of SO processes is critical for improving decadal climate predictions globally and for addressing longstanding issues with coupled climate model simulations of recent Earth system change.

Abstract Background The oXiris is a novel filter for continuous renal replacement therapy (CRRT) featuring an adsorption coating to adsorb endotoxins and remove inflammatory mediators. Given that no consensus has been reached on its potential benefits in treating sepsis, a meta-analysis was conducted to assess its impact on the clinical outcomes of this patient population. Methods Eleven databases were retrieved to find relevant observational studies and randomized controlled trials. The Newcastle–Ottawa Scale and the Cochrane Risk of Bias Tool were used to assess the quality of the included studies. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was employed to assess the certainty of evidence. The 28-day mortality was the primary outcome. Secondary outcomes were 7-, 14-, and 90-day mortality, length of intensive care unit (ICU) and hospital stay, ICU and hospital mortality, norepinephrine (NE) dose, interleukin-6 (IL-6) and lactate levels, and Sequential Organ Failure Assessment (SOFA) score. Results The meta-analysis, pooling data from 14 studies, involving 695 patients, showed significant reductions in 28-day mortality [odds ratio (OR) 0.53; 95% confidence interval (CI) 0.36–0.77, p = 0.001] and length of ICU stay [weighted mean difference (WMD) − 1.91; 95% CI − 2.56 to − 1.26, p

The traditional Langmuir equation displays drawback in accurately characterizing the methane adsorption behavior in coal, due to it assuming the uniform surface of coal pores. Additionally, the decay law of gas adsorption capacity with an increasing coal reservoir temperature remains unknown. In this study, the fractal adsorption model is proposed based on the fractal dimension (Df) of coal pores and the attenuation coefficient (n) of the adsorption capacity. The principles and methods of this fractal adsorption model are deduced and summarized in detail. The results show that the pore structures of the two coal samples exhibit obvious fractal characteristics, with the values of fractal dimensions (Df) being 2.6279 and 2.93. The values of adsorption capacity attenuation coefficients (n) are estimated as −0.006 and −0.004 by the adsorption experiments with different temperatures. The proposed fractal adsorption model presents a greater theoretical significance and higher accuracy than that of the Langmuir equation. The accuracy of the fractal adsorption model with temperature effect dependence is verified, establishing a prediction method for methane adsorption capacity in deep coal reservoirs. This study can serve as a theoretical foundation for coalbed methane exploration and development, as well as provide valuable insights for unconventional natural gas exploitation.

The targeted stimulation of micropores based on the transformation of coal’s molecular structure is proposed due to the chemical properties and difficult-to-transform properties of micropores. Carbon disulfide (CS2) extraction is used as a targeted stimulation to reveal the internal evolution mechanism of micropore transformation. The variations of microcrystalline structures and micropores of bituminous coal and anthracite extracted by CS2 were analyzed with X-ray diffraction (XRD), low-temperature carbon dioxide (CO2) adsorption, and molecular simulation. The results show that CS2 extraction, with the broken chain effect, swelling effect, and aromatic ring rearrangement effect, can promote micropore generation of bituminous coal by transforming the microcrystalline structure. Furthermore, CS2 extraction on bituminous coal can decrease the average micropore size and increase the micropore volume and area. The aromatic layer fragmentation effect of CS2 extraction on anthracite, compared to the micropore generation effect of the broken chain effect and swelling effect, can enlarge micropores more remarkably, as it induces an enhancement in the average micropore size and a decline in the micropore volume and area. The research is expected to provide a theoretical basis for establishing reservoir stimulation technology based on CS2 extraction.

To analyze the transformed effect of three-dimensional (3D) fracture in coal by CO2 phase transition fracturing (CO2-PTF), the CO2-PTF experiment under a fracturing pressure of 185 MPa was carried out. Computed Tomography (CT) scanning and fractal theory were used to analyze the 3D fracture structure parameters. The fractal evolution characteristics of the 3D fractures in coal induced by CO2-PTF were analyzed. The results indicate that the CO2 phase transition fracturing coal has the fracture generation effect and fracture expansion-transformation effect, causing the maximum fracture length, fracture number, fracture volume and fracture surface area to be increased by 71.25%, 161.94%, 3970.88% and 1330.03%. The fractal dimension (DN) for fracture number increases from 2.3523 to 2.3668, and the fractal dimension (DV) for fracture volume increases from 2.8440 to 2.9040. The early dynamic high-pressure gas jet stage of CO2-PTF coal influences the fracture generation effect and promotes the generation of 3D fractures with a length greater than 140 μm. The subsequent quasi-static high-pressure gas stage influences the fracture expansion-transformation effect, which promotes the expansion transformation of 3D fractures with a length of less than 140 μm. The 140 μm is the critical value for the fracture expansion-transformation effect and fracture generation effect. Five indicators are proposed to evaluate the 3D fracture evolution in coal caused by CO2-PTF, which can provide theoretical and methodological references for the study of fracture evolution characteristics of other unconventional natural gas reservoirs and their reservoir stimulation.

Abstract Atlantic Niño, the dominant climate mode in the equatorial Atlantic, is known to remotely force a La Niña-like response in the Pacific, potentially affecting seasonal climate predictions. Here, we use both observations and large-ensemble simulations to explore the physical mechanisms linking the Atlantic to the Pacific. Results indicate that an eastward propagating atmospheric Kelvin wave from the Atlantic, through the Indian Ocean, to the Pacific is the primary pathway. Interaction of this Kelvin wave with the orography of the Maritime Continent induces orographic moisture convergence, contributing to the generation of a local Walker Cell over the Maritime Continent-Western Pacific area. Moreover, land friction over the Maritime Continent dissipates Kelvin wave energy, affecting the strength of the Bjerknes feedback and thus the development of the La Niña-like response. Therefore, improving the representation of land–atmosphere–ocean interactions over the Maritime Continent may be fundamental to realistically simulate Atlantic Niño’s impact on El Niño-Southern Oscillation.

Abstract Ocean warming is a key factor impacting future changes in climate. Here we investigate vertical structure changes in globally averaged ocean heat content (OHC) in high‐ (HR) and low‐resolution (LR) future climate simulations with the Community Earth System Model (CESM). Compared with observation‐based estimates, the simulated OHC anomalies in the upper 700 and 2,000 m during 1960–2020 are more realistic in CESM‐HR than ‐LR. Under RCP8.5 scenario, the net surface heat into the ocean is very similar in CESM‐HR and ‐LR. However, CESM‐HR has a larger increase in OHC in the upper 250 m compared to CESM‐LR, but a smaller increase below 250 m. This difference can be traced to differences in eddy‐induced vertical heat transport between CESM‐HR and ‐LR in the historical period. Moreover, our results suggest that with the same heat input, upper‐ocean warming is likely to be underestimated by most non‐eddy‐resolving climate models.

Abstract It has been widely recognized that tropical cyclone (TC) genesis requires favorable large‐scale environmental conditions. Based on these linkages, numerous efforts have been made to establish an empirical relationship between seasonal TC activities and large‐scale environmental favorability in a quantitative way, which lead to conceptual functions such as the TC genesis index. However, due to the limited amount of reliable TC observations and complexity of the climate system, a simple analytic function may not be an accurate portrait of the empirical relationship between TCs and their ambiences. In this research, we use convolution neural networks (CNNs) to disentangle this complex relationship. To circumvent the limited amount of seasonal TC observation records, we implement transfer‐learning technique to train ensemble of CNNs first on suites of high‐resolution climate model simulations with realistic seasonal TC activities and large‐scale environmental conditions, and then on a state‐of‐the‐art reanalysis from 1950 to 2019. The trained CNNs can well reproduce the historical TC records and yields significant seasonal prediction skills when the large‐scale environmental inputs are provided by operational climate forecasts. Furthermore, by inputting the ensemble CNNs with 20th century reanalysis products and Phase 6 of the Coupled Model Intercomparison Project (CMIP6) simulations, we investigated TC variability and its changes in the past and future climates. Specifically, our ensemble CNNs project a decreasing trend of global mean TC activity in the future warming scenario, which is consistent with our future projections using high‐resolution climate model.

Projected changes in upwelling favorable winds in eastern boundary upwelling systems will compete with warming due to enhanced heat transport from the tropics and drive complex responses in upwelling and impact important fisheries, according to high-resolution climate simulations.

A new stalagmite record from northern Italy and other published data from Europe and northern Africa reveals a split in the climatological westerlies during the early LIA, possibly attributed to sea ice melting.

BackgroundVitamin D deficiency is common in critically ill patients with suspected infection and is strongly associated with the predisposition of sepsis and a poor prognosis. The effectiveness of vitamin D supplementation for preventing sepsis remains unclear. This retrospective cohort study investigated the effect of vitamin D supplementation on sepsis prophylaxis in critically ill patients with suspected infection.MethodsThis retrospective cohort study included 19,816 adult patients with suspected infection in intensive care units (ICU) from 2008 to 2019 at the Beth Israel Deaconess Medical Center, Boston, USA. The included patients were divided into the vitamin D cohort or non-vitamin D cohort according to vitamin D administration status. The primary outcomes were the incidence of sepsis in ICU. The secondary outcomes included 28-day all-cause mortality, length of ICU and hospital stay and the requirements of vasopressors or mechanical ventilation. A propensity score matching cohort was used to test the differences in primary and secondary outcomes between groups.ResultsThe results showed that vitamin D supplementation demonstrated a lower risk of sepsis (odd ratio 0.46; 95% CI 0.35–0.60; P < 0.001) and a lower risk of new mechanical ventilation requirement (odd ratio 0.70; 95% CI 0.53-0.92; P = 0.01), but no significant difference in the risk of 28-day mortality was observed (hazard ratio 1.02; 95% CI 0.77–1.35; P = 0.89). In the sensitive analysis, among the patients who suspected infection within 24 h before or after ICU admission, a lower risk of sepsis and a lower percentage of new mechanical ventilation also were detected in the vitamin D cohort.ConclusionVitamin D supplementation may have a positively prophylactic effect on sepsis in critically ill patients with suspected infection.

The differences in spatial-temporal distribution patterns and dominant driving factors of vegetation evolution among sub-regions during different historical periods were not clear. Therefore, this study introduced the gravity center model and geodetector to analyze the spatial-temporal change characteristics and dominant driving factors of normalized difference vegetation index (NDVI) in China during 1981–2019 from the perspective of geographic divisions. Results showed that (1) during 1981–2019, the average vegetation coverage in China showed an increasing trend and zones with obviously increasing vegetation NDVI were mainly distributed in the middle reaches of the Yellow River basin and the upper reaches of the Yangtze River. (2) During 1981–2019, the gravity center of national vegetation NDVI was mainly concentrated in Yan’an City and Tongchuan City, showing a southward migration trend as a whole, which indicates that the increment and growth rates of the southern part were greater than those of the northern part. (3) The growth of vegetation in southern China was primarily affected by the temperature, while that of northern China was largely influenced by precipitation. (4) During 1981–2019, the dominant interactive factors of vegetation change for all subregions changed greatly: natural factor (climate or terrain) ∩ other factors → landuse ∩ other factors.

Abstract Background Previous cluster-randomized controlled trials evaluating the impact of implementing evidence-based guidelines for nutrition therapy in critical illness do not consistently demonstrate patient benefits. A large-scale, sufficiently powered study is therefore warranted to ascertain the effects of guideline implementation on patient-centered outcomes. Methods We conducted a multicenter, cluster-randomized, parallel-controlled trial in intensive care units (ICUs) across China. We developed an evidence-based feeding guideline. ICUs randomly allocated to the guideline group formed a local "intervention team", which actively implemented the guideline using standardized educational materials, a graphical feeding protocol, and live online education outreach meetings conducted by members of the study management committee. ICUs assigned to the control group remained unaware of the guideline content. All ICUs enrolled patients who were expected to stay in the ICU longer than seven days. The primary outcome was all-cause mortality within 28 days of enrollment. Results Forty-eight ICUs were randomized to the guideline group and 49 to the control group. From March 2018 to July 2019, the guideline ICUs enrolled 1399 patients, and the control ICUs enrolled 1373 patients. Implementation of the guideline resulted in significantly earlier EN initiation (1.20 vs. 1.55 mean days to initiation of EN; difference − 0.40 [95% CI − 0.71 to − 0.09]; P = 0.01) and delayed PN initiation (1.29 vs. 0.80 mean days to start of PN; difference 1.06 [95% CI 0.44 to 1.67]; P = 0.001). There was no significant difference in 28-day mortality (14.2% vs. 15.2%; difference − 1.6% [95% CI − 4.3% to 1.2%]; P = 0.42) between groups. Conclusions In this large-scale, multicenter trial, active implementation of an evidence-based feeding guideline reduced the time to commencement of EN and overall PN use but did not translate to a reduction in mortality from critical illness. Trial registration: ISRCTN, ISRCTN12233792 . Registered November 20th, 2017.

Background: In preclinical experiments, we demonstrated that the 5-HT3 receptor antagonist granisetron results in reduced inflammation and improved survival in septic mice. This randomized controlled trial was designed to assess the efficacy and safety of granisetron in patients with sepsis.Methods: Adult patients with sepsis and procalcitonin ≥ 2 ng/ml were randomized in a 1:1 ratio to receive intravenous granisetron (3 mg every 8 h) or normal saline at the same volume and frequency for 4 days or until intensive care unit discharge. The primary outcome was 28-day all-cause mortality. Secondary outcomes included the duration of supportive therapies for organ function, changes in sequential organ failure assessment scores over 96 h, procalcitonin reduction rate over 96 h, the incidence of new organ dysfunction, and changes in laboratory variable over 96 h. Adverse events were monitored as the safety outcome.Results: The modified intention-to-treat analysis included 150 septic patients. The 28-day all-cause mortalities in the granisetron and placebo groups were 34.7% and 35.6%, respectively (odds ratio, 0.96; 95% CI, 0.49–1.89). No differences were observed in secondary outcomes. In the subgroup analysis of patients without abdominal or digestive tract infections, the 28-day mortality in the granisetron group was 10.9% lower than mortality in the placebo group. Adverse events were not statistically different between the groups.Conclusion: Granisetron did not improve 28-day mortality in patients with sepsis. However, a further clinical trial targeted to septic patients without abdominal/digestive tract infections perhaps is worthy of consideration.

How the Central American mountains influence tropical cyclone (TC) development in the eastern North Pacific is not well understood. Here, the authors use model simulations to show that on a seasonal timescale, these mountains interrupt moisture transport from the Caribbean Sea and as a result, reduce TC activity by up to 35%.

In order to reveal the process and mechanism of gas flow in a low-permeability coal seam, a new multiple-relaxation-time lattice Boltzmann method (MRT-LBM) model of gas migration in coal micro/nanopores based on Langmuir monolayer adsorption theory, the slip boundary scheme and Bosanquet effective viscosity was established. The software MATLAB was used to carry out the simulation study of uniform pore gas flow based on the MRT-LBM model, and the results were compared and verified with the porous anodic alumina membrane gas flow experimental results. On this basis, the gas flow in coal pores with different micro/nanopore sizes considering adsorption was simulated. The results show that the dimensionless permeability coefficient increases with decreasing pore size under the same pressure, which reflects the subsequent enhancement of the microboundary constraint effect and reveals that the pore system becomes the main controlling factor of coal seam permeability within the coal matrix in the middle and late stages of coal seam gas extraction, while the role of the microboundary constraint effect needs to be considered. The gas adsorption layer weakens the pore gas flow capacity, but for pores with a radius greater than 16 nm, the apparent change in permeability caused by the adsorption layer is less than 5%, and the adsorption effect can be ignored. N2, CH4, and CO2 enter the transition flow regime under different pressure conditions; with gas extraction, the gas pressure decreases, and the difference in the gas flow characteristics of the three gases increases.

Abstract The Intergovernmental Panel on Climate Change Fifth Assessment Report lists sea‐level rise as one of the major future climate challenges. Based on pre‐industrial and historical‐and‐future climate simulations with the Community Earth System Model, we analyze the projected sea‐level rise in the Northwest Atlantic Ocean with two sets of simulations at different horizontal resolutions. Compared with observations, the low resolution (LR) model simulated Gulf Stream does not separate from the shore but flows northward along the entire coast, causing large biases in regional dynamic sea level (DSL). The high resolution (HR) model improves the Gulf Stream representation and reduces biases in regional DSL. Under the RCP8.5 future climate scenario, LR projects a DSL trend of 1.5–2 mm/yr along the northeast continental shelf (north of 40° N), which is 2–3 times the trend projected by HR. Along the southeast shelf (south of 35° N), HR projects a DSL trend of 0.5–1 mm/yr while the DSL trend in LR is statistically insignificant. The different spatial patterns of DSL changes are attributable to the different Gulf Stream reductions in response to a weakening Atlantic Meridional Overturning Circulation. Due to its poor representation of the Gulf Stream, LR projects larger (smaller) current decreases along the north (south) east continental slope compared to HR. This leads to larger (smaller) trends of DSL rise along the north (south) east shelf in LR than in HR. The results of this study suggest that the better resolved ocean circulations in HR can have significant impacts on regional DSL simulations and projections.

Atmospheric rivers are responsible for much of the poleward water vapour transport in the mid-latitudes and can cause extreme precipitation after landfall. Here, the authors show that ocean fronts and eddies can influence atmospheric rivers and increase the associated precipitation along the North American west coast.

Summary: Pancreatic cancer is a deadly disease that accounts for approximately 5% of cancer deaths worldwide, with a dismal 5-year survival rate of 10%. Known genetic risk factors explain only a modest proportion of the heritable risk of pancreatic cancer. We conducted a whole-exome case-control sequencing study in 1,591 pancreatic cancer cases and 2,134 cancer-free controls of European ancestry. In our gene-based analysis, ATM ranked first, with a genome-wide significant p value of 1 × 10−8. The odds ratio for protein-truncating variants in ATM was 24, which is substantially higher than prior estimates, although ours includes a broad 95% confidence interval (4.0–1000). SIK3 was the second highest ranking gene (p = 3.84 × 10−6, false discovery rate or FDR = 0.032). We observed nominally significant association signals in several genes of a priori interest, including BRCA2 (p = 4.3 × 10−4), STK11 (p = 0.003), PALB2 (p = 0.019), and TP53 (p = 0.037), and reported risk estimates for known pathogenic variants and variants of uncertain significance (VUS) in these genes. The rare variants in established susceptibility genes explain approximately 24% of log familial relative risk, which is comparable to the contribution from established common susceptibility variants (17%). In conclusion, this study provides new insights into the genetic susceptibility of pancreatic cancer, refining rare variant risk estimates in known pancreatic cancer susceptibility genes and identifying SIK3 as a novel candidate susceptibility gene. This study highlights the prominent importance of ATM truncating variants and the underappreciated role of VUS in pancreatic cancer etiology.

In 2012, the International Agency for Research on Cancer (IARC) classified diesel particulate matter (DPM) as a carcinogen to human. With the increased usage of diesel equipment in underground mines, miners have a high risk of over-exposure to DPM, which has drawn many concerns from the public. This study used computational fluid dynamics (CFD) to analyse the DPM dispersion and concentration distribution characteristics in an underground development face based on an onsite experiment. The DPM emitted from a moving loader under a forcing auxiliary ventilation system was simulated. The motion of the load-haul-dump (LHD) in the tunnel was represented by a dynamic mesh method. The species transport approach was applied to study the DPM behaviours. High DPM concentration zones were then identified based on the simulation results. The results could provide guidelines for work practices and be helpful to an optimum auxiliary ventilation design to reduce underground miner exposure.

Abstract Turbulent vertical mixing in the stratified ocean interior has a huge impact on global ocean circulations and the climate system. Although parameterizations of vertical mixing furnished by internal tides have been built into state‐of‐the‐art coupled global climate models (CGCMs), efforts in parameterizing wind‐driven vertical mixing in CGCMs are still limited. In this study, we apply a modified finescale parameterization (MFP) to an eddy‐resolving Community Earth System Model (CESM) to represent the wind's contribution to vertical mixing in the stratified ocean interior. The spatial pattern of the MFP‐parameterized wind‐driven vertical mixing in the thermocline agrees with the observation derived from the finestructure measurements of Argo floats, reproducing the enhanced values in the Kuroshio, Gulf Stream extensions, and the Southern Ocean where the winds inject great amount of energy into the internal wave field. The MFP also captures the observed seasonal variation of wind‐driven vertical mixing in the thermocline of these regions that exhibits enhancement and weakening in winter and summer, respectively. Application of the MFP to a non‐eddy‐resolving CESM fails to reproduce the observed wind‐driven vertical mixing. Specifically, the magnitude of parameterized wind‐driven vertical mixing in the thermocline of Kuroshio, Gulf Stream extensions, and the Southern Ocean is systemically smaller than those in the observation and eddy‐resolving CESM; so is the case for the amplitude of seasonal cycle. The results highlight the benefit of eddy‐resolving CESM compared to its standard‐resolution counterpart in parameterizing the wind‐driven vertical mixing and provide insight into developing parameterizations for wind‐driven vertical mixing in eddy‐resolving CGCMs.

Abstract This study further evaluates the modeling approach of Jia et al. (2019), https://doi.org/10.1029/2019gl081960 (JEA19) to investigate the potential effects of mesoscale sea surface temperature (SST) variability on the atmospheric circulation. The approach employs a global atmospheric circulation model coupled to a slab ocean model to produce two ensembles of simulations: one in which the SST exhibits realistic mesoscale variability, and another in which the mesoscale SST variability is suppressed. The results of the present study suggest that the modeling approach yields the desired SST differences between the two ensembles at the mesoscales. They also show, however, that the approach can lead to undesirable SST differences at the large scales, if the prescribed pair of oceanic heat flux fields have large scale differences. In the experiments of JEA19, such forced, large scale SST differences dominate over the large scale differences that may develop in response to changes in the large scale atmospheric circulation by nonlinear interactions with the SST. This result suggests that finding a proper pair of estimates of the oceanic heat flux fields is necessary for the investigation of the potential upscale impact of mesoscale SST variability on the atmosphere by the approach of JEA19. The paper concludes with proposing a potential improved strategy to obtain such a pair of estimates.

THC has been used as a promising treatment approach for neurological disorders, but the highly psychoactive effects have largely warned off many scientists from pursuing it further. We conducted an intranasal treatment using low-dose THC on 12-month-old APP/PS1 mice daily for 3 months to overcome any potential psychoactive response induced by the systemic delivery. Our results demonstrate that the THC nasal treatment at 0.002 and 0.02 mg/kg significantly slowed the memory decline compared to that in the vehicle-treated transgenic mouse control group. An enzyme-linked immunosorbent assay showed that the Aβ1–40 and 1–42 peptides decreased in the THC-treated groups. The Western blot data indicate that long-term low-dose THC intranasal administration promoted p-tau level reduction and mitochondrial function marker redistribution. The blood biochemical parameter data demonstrate some insignificant changes in cytokine, immunoglobulin, and immune cell profiles during intranasal THC treatment. Intranasal delivery is a non-invasive and convenient method that rapidly targets therapeutics to the brain, minimizing systemic exposure to avoid unwanted adverse effects. Our study provides new insights into the role of low-dose THC intranasal treatment as a pharmacological strategy to counteract alterations in Alzheimer’s disease-related cognitive performance.

Abstract We present an unprecedented set of high‐resolution climate simulations, consisting of a 500‐year pre‐industrial control simulation and a 250‐year historical and future climate simulation from 1850 to 2100. A high‐resolution configuration of the Community Earth System Model version 1.3 (CESM1.3) is used for the simulations with a nominal horizontal resolution of 0.25° for the atmosphere and land models and 0.1° for the ocean and sea‐ice models. At these resolutions, the model permits tropical cyclones and ocean mesoscale eddies, allowing interactions between these synoptic and mesoscale phenomena with large‐scale circulations. An overview of the results from these simulations is provided with a focus on model drift, mean climate, internal modes of variability, representation of the historical and future climates, and extreme events. Comparisons are made to solutions from an identical set of simulations using the standard resolution (nominal 1°) CESM1.3 and to available observations for the historical period to address some key scientific questions concerning the impact and benefit of increasing model horizontal resolution in climate simulations. An emerging prominent feature of the high‐resolution pre‐industrial simulation is the intermittent occurrence of polynyas in the Weddell Sea and its interaction with an Interdecadal Pacific Oscillation. Overall, high‐resolution simulations show significant improvements in representing global mean temperature changes, seasonal cycle of sea‐surface temperature and mixed layer depth, extreme events and in relationships between extreme events and climate modes.

Abstract A multimodel, multiresolution ensemble using Coupled Model Intercomparison Project Phase 6 (CMIP6) High Resolution Model Intercomparison Project (HighResMIP) coupled experiments is used to assess the performance of key aspects of the North Atlantic circulation. The Atlantic Meridional Overturning Circulation (AMOC), and related heat transport, tends to become stronger as ocean model resolution is enhanced, better agreeing with observations at 26.5°N. However, for most models the circulation remains too shallow compared to observations and has a smaller temperature contrast between the northward and southward limbs of the AMOC. These biases cause the northward heat transport to be systematically too low for a given overturning strength. The higher‐resolution models also tend to have too much deep mixing in the subpolar gyre. In the period 2015–2050 the overturning circulation tends to decline more rapidly in the higher‐resolution models, which is related to both the mean state and to the subpolar gyre contribution to deep water formation. The main part of the decline comes from the Florida Current component of the circulation. Such large declines in AMOC are not seen in the models with resolutions more typically used for climate studies, suggesting an enhanced risk for Northern Hemisphere climate change. However, only a small number of different ocean models are included in the study.

Abstract Background There is a lack of large-scale epidemiological data on the clinical practice of enteral nutrition (EN) feeding in China. This study aimed to provide such data on Chinese hospitals and to investigate factors associated with EN delivery. Methods This cross-sectional study was launched in 118 intensive care units (ICUs) of 116 mainland hospitals and conducted on April 26, 2017. At 00:00 on April 26, all patients in these ICUs were included. Demographic and clinical variables of patients on April 25 were obtained. The dates of hospitalization, ICU admission and nutrition initiation were reviewed. The outcome status 28 days after the day of investigation was obtained. Results A total of 1953 patients were included for analysis, including 1483 survivors and 312 nonsurvivors. The median study day was day 7 (IQR 2–19 days) after ICU entry. The proportions of subjects starting EN within 24, 48 and 72 h after ICU entry was 24.8% (84/352), 32.7% (150/459) and 40.0% (200/541), respectively. The proportion of subjects receiving > 80% estimated energy target within 24, 48, 72 h and 7 days after ICU entry was 10.5% (37/352), 10.9% (50/459), 11.8% (64/541) and 17.8% (162/910), respectively. Using acute gastrointestinal injury (AGI) 1 as the reference in a Cox model, patients with AGI 2–3 were associated with reduced likelihood of EN initiation (HR 0.46, 95% CI 0.353–0.599; p

BackgroundUlinastatin has been prescribed to treat sepsis. However, there is doubt regarding the extent of any improvement in outcomes to guide future decision making.ObjectivesTo evaluate the effects of ulinastatin on mortality and related outcomes in sepsis patients.MethodsThirteen randomized controlled trials and two prospective studies published before September 1, 2018, that included 1358 patients with sepsis, severe sepsis, or septic shock were evaluated. The electronic databases searched in this study were PubMed, Medline, Embase, and China National Knowledge Infrastructure (CNKI) for Chinese Technical Periodicals.ResultsUlinastatin significantly decreased the all-cause mortality {odds ratio (OR) = 0.48, 95% confidence interval (CI) [0.35, 0.66], p < 0.00001, I2 = 13%}, Acute Physiology, Age, Chronic Health Evaluation II (APACHE II) score {mean difference (MD) = -3.18, 95%CI [-4.01, -2.35], p < 0.00001, I2 = 33%, and reduced the incidence of multiple organ dysfunction syndrome (MODS) (OR = 0.3, 95% CI [0.18, 0.49], p < 0.00001, I2 = 0%). Ulinastatin also decreased the serum levels of IL-6 (MD = -53.00, 95% CI [-95.56, -10.05], p = 0.02), TNF-a MD = -53.05, 95%CI [-68.36, -37.73], p < 0.00001, and increased the serum levels of IL-10 (MD = 37.73, 95% CI [16.92, 58.54], p = 0.0004). Ulinastatin administration did not lead to any difference in the occurrence of adverse events.ConclusionsUlinastatin improved all-cause mortality and other related outcomes in patients with sepsis or septic shock. The results of this meta-analysis suggest that ulinastatin may be an effective treatment for sepsis and septic shock.

Background/Aims: Continuous renal replacement therapy (CRRT) is a treatment for acute kidney injury (AKI) patients. It has become a controversy about whether patients with liver dysfunction should perform CRRT with regional citrate anticoagulation (RCA). Methods: This retrospective observational study enrolled 145 AKI patients (275 CRRT sessions) who received CRRT with RCA and had no history of chronic liver disease. Circuit survival time, blood pressure, trans-membrane pressure (TMP), acid-base and electrolyte status were recorded and analyzed. The severity of liver dysfunction was determined by total bilirubin (TBil) and international normalized ratio (INR), while the accumulation degree of citrates was quantified by total/ ionized calcium (tCa/iCa) raito. Results: Our results showed that there was no correlation of tCa/iCa ratio with TBil or INR. And tCa/iCa ratio was not related to the disturbances of pH, lactates, sodium, magnesium, blood pressure or TMP despite that high tCa/iCa ratios might be related to the decrease of circuit survival time. TBil did not correlate with the above indexes, except for lactates levels. INR did not correlate with the above indexes except for lactates levels and blood pressure. In addition, neither was TBil, INR, nor tCa/iCa ratio, related with fatal outcomes (22.76% of the patients). Conclusion: The present study demonstrated that, with proper monitoring and adjustment of citrates and calcium infusion, applying RCA in CRRT is reasonably safe for AKI patients with acute liver dysfunction, as long as circuit time stays below roughly 50 hours.

Abstract Background Sepsis is a major challenge in critical care and is associated with high mortality. Current management of sepsis and septic shock remains mainly supportive. Both basic and clinical research has shown that ulinastatin can improve the prognosis of sepsis. The aim of this trial is to evaluate the efficacy and safety profiles of ulinastatin compared with placebo. Methods/design In this multi-center, double-blind, randomized placebo-controlled trial we are recruiting a total of 348 subjects meeting “The Third International Consensus Definitions for Sepsis and Septic Shock” (Sepsis-3). Subjects will be randomized (1:1) to receive ulinastatin 400,000 IU three times a day for 10 days or matching placebo and usual care simultaneously. The primary outcome is 28-day all-cause mortality. Adverse events and serious adverse events will be monitored closely. Discussion ADJUST is a large, multi-center, double-blind, randomized, parallel-group, placebo-controlled trial of ulinastatin in mainland China and is well-designed on the basis of previous studies. The results of this trial may help to provide evidence-based recommendations for treatment of sepsis. Trial registration ClinicalTrials.gov, ID: NCT02647554. First registered on 27 December 2015, and last verified in December of 2016. Protocol version: 2.1, verified on 19 July 2016.

The increasing use of diesel-powered equipment in confined spaces (underground mines) has the potential to over expose underground miners under the threat of diesel particulate matter (DPM). Miners in underground mines can be exposed to DPM concentrations far more than works in other industries. A great number of animal and epidemiological studies have shown that both short-term and long-term DPM exposure have adverse health effect. Based on reviews of related studies, especially some recent evidence, this paper investigated the long and short-term health effects based on animal studies and epidemiological studies. The exposure-response relationship studies were also explored and compared to the current DPM regulation or standards in some countries. This paper found that the DPM health effect studies specifically for miners are not sufficient to draw solid conclusions, and a recommendation limit of DPM concentration can be put in place for better protection of miners from DPM health risk. Current animal studies lack the use of species that have similar lung functions as human for understanding the cancer mode of action in human. And finally, the DPM health hazard will continue to be a challenging topic before the mode of action and reliable exposure-response relationship are established. Keywords: Diesel particulate matter (DPM), Underground mines, Lung cancer, Exposure-response relationship

Background/Aims: This study investigated signaling pathways via which extracellular histones induce the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) release from the macrophage cell line RAW 264.7 and the anti-inflammatory efficacy of the antioxidant alpha-lipoic acid (ALA). Methods: ELISA and western blotting analyses were conducted to detect the release of TNF-α from histone-stimulated RAW 264.7 macrophages and the associated phospho-activation of MAPKs (ERK and p38) and NF-κB p65. The effects of ALA on the release of TNF-α and phospho-activation of the MAPKs and NF-κB p65 were studied. P < 0.05 was considered statistically significant. Results: Extracellular histones dose-dependently induced TNF-α release from RAW 264.7 cells and increased the phosphorylation of p38, ERK, and NF-κB p65. TNF-α release was markedly suppressed by p38, ERK, and NF-kB inhibitors. ALA reduced histone-induced TNF-α release, ERK/p38 MAPK activation, and NF-kB activation without affecting macrophage viability. Conclusion: Histones induce TNF-α release from macrophages by activating the MAPK and NF-kB signaling pathways, while ALA suppresses this response by inhibiting ERK, p38 and NF-kB. These findings identify potentially critical inflammatory signaling pathways in sepsis and molecular targets for sepsis treatment.

Abstract Hurricane Patricia in 2015 was the strongest Pacific hurricane to make landfall in Mexico. Although Patricia fortuitously spared major cities, it reminded us of the threat tropical cyclones (TCs) pose in the eastern North Pacific (ENP) and the importance of improving our understanding and prediction of ENP TCs. Patricia’s intensity and the active 2015 ENP hurricane season have been partially attributed to the strong El Niño in 2015, however there is still a lack of fundamental understanding of the relationship between El Niño-Southern Oscillation (ENSO) and ENP TCs. Here, we demonstrate that ENSO drives intrabasin variability of ENP TCs, with enhanced (reduced) TC frequency in the western portion of the ENP during El Niño (La Niña), but reduced (enhanced) TC frequency in the eastern nearshore area, where landfalling TCs preferentially form. This intrabasin difference is primarily driven by the Central American Gap Winds (CAGW), which intensify (weaken) during El Niño (La Niña), producing low-level anticyclonic (cyclonic) relative vorticity anomalies and thus an unfavorable (favorable) environment for TC genesis. These findings shed new light on the dynamics linking ENP TC activity to ENSO, and highlight the importance of improving CAGW representation in models to make skillful seasonal forecasts of ENP TCs.