The boreal summer Asian monsoon has been evaluated in 25 Coupled Model Intercomparison Project-5 (CMIP5) and 22 CMIP3 GCM simulations of the late twentieth Century. Diagnostics and skill metrics have ...been calculated to assess the time-mean, climatological annual cycle, interannual variability, and intraseasonal variability. Progress has been made in modeling these aspects of the monsoon, though there is no single model that best represents all of these aspects of the monsoon. The CMIP5 multi-model mean (MMM) is more skillful than the CMIP3 MMM for all diagnostics in terms of the skill of simulating pattern correlations with respect to observations. Additionally, for rainfall/convection the MMM outperforms the individual models for the time mean, the interannual variability of the East Asian monsoon, and intraseasonal variability. The pattern correlation of the time (pentad) of monsoon peak and withdrawal is better simulated than that of monsoon onset. The onset of the monsoon over India is typically too late in the models. The extension of the monsoon over eastern China, Korea, and Japan is underestimated, while it is overestimated over the subtropical western/central Pacific Ocean. The anti-correlation between anomalies of all-India rainfall and Niño3.4 sea surface temperature is overly strong in CMIP3 and typically too weak in CMIP5. For both the ENSO-monsoon teleconnection and the East Asian zonal wind-rainfall teleconnection, the MMM interannual rainfall anomalies are weak compared to observations. Though simulation of intraseasonal variability remains problematic, several models show improved skill at representing the northward propagation of convection and the development of the tilted band of convection that extends from India to the equatorial west Pacific. The MMM also well represents the space–time evolution of intraseasonal outgoing longwave radiation anomalies. Caution is necessary when using GPCP and CMAP rainfall to validate (1) the time-mean rainfall, as there are systematic differences over ocean and land between these two data sets, and (2) the timing of monsoon withdrawal over India, where the smooth southward progression seen in India Meteorological Department data is better realized in CMAP data compared to GPCP data.
Background and Objective
Resistin was recently reported to play a role in inflammation‐related diseases such as arthritis. However, the precise role of resistin in chronic inflammatory diseases, such ...as periodontal disease, remains unclear. The aim of this study was to investigate the combined effects of nicotine and lipopolysaccharide (LPS) on the expression of resistin and to assess whether resistin expression influences the levels of inflammatory cytokines, extracellular matrix (ECM) molecules and MMPs in human periodontal ligament cells (PDLCs) stimulated with both nicotine and LPS.
Material and Methods
PDLCs were pretreated with isoproterenol or resistin‐specific small interfering RNA (siRNA), stimulated with LPS plus nicotine for 24 h, and then monitored for the production of inflammatory mediators. The concentrations of prostaglandin E2 (PGE2) and nitric oxide (NO) were measured by radioimmunoassay and the Griess method, respectively. RT‐PCR and western blot analysis were used to measure the levels of mRNA and protein, respectively. Western blot analysis was also used to assess the activation of various signal‐transduction pathways.
Results
Treatment with nicotine plus LPS up‐regulated the expression of resistin mRNA and the production of resistin protein in PDLCs in a time‐ and concentration‐dependent manner. Isoproterenol‐mediated interference with the function of resistin, or siRNA‐mediated knockdown of resistin expression, markedly attenuated the LPS plus nicotine‐mediated stimulation of PGE2 and NO production, the production of cyclooxygenase‐2 (COX‐2) and inducible nitric oxide synthase proteins and the expression of proinflammatory cytokines tumor necrosis factor‐α, interleukin (IL)‐1β, IL‐6 and IL‐12 and MMPs (MMP‐1, MMP‐2 and MMP‐9); however, these treatments restored the expression of ECM molecules. Furthermore, pretreatment with isoproterenol or resistin‐specific siRNA blocked nicotine plus LPS‐induced activation of phosphoinositide‐3‐kinase, glycogen synthase kinase‐3 beta, β‐catenin, p38, ERK, JNK and nuclear factor‐κB.
Conclusion
This is the first study to show that the inhibition of resistin, by either a pharmacological or a genetic silencing approach, has anti‐inflammatory effects. These effects include decreased levels of inflammatory cytokines and the prevention of ECM breakdown in a nicotine plus LPS‐stimulated PDLC model.
Subgingival microorganisms are potentially associated with periodontal diseases. However, changes in the subgingival microbiota during the progress of periodontal diseases are poorly understood. In ...this study, we analyzed bacterial communities in the subgingival paper point samples from 32 Korean individuals with no sign of disease, gingivitis, or periodontitis using 454 FLX Titanium pyrosequencing. A total of 256,113 reads representing 26 phyla, 433 genera, and 1,016 species were detected. Bacteroidetes, Fusobacteria, Synergistetes, and Spirochaetes were the abundant phyla in periodontitis subjects, whereas Firmicutes and Proteobacteria were identified as the dominant phyla in the gingivitis and healthy subjects, respectively. Although high levels of Porphyromonas, Fusobacterium, Fretibacterium, Rothia, Filifactor, and Treponema genera were observed in the periodontitis subjects, Streptococcus, Capnocytophaga, Leptotrichia, and Haemophilus genera were found at high frequency in the gingivitis subjects. Species including Porphyromonas gingivalis, Fusobacterium nucleatum, and Fretibacterium fastidiosum were significantly increased in periodontitis subjects. On the other hand, Streptococcus pseudopneumoniae, Haemophilus parainfluenzae, and Leptotrichia hongkongensis were preferentially observed in the gingivitis subjects. Intriguingly, the halophile Halomonas hamiltonii was revealed as a predominant species in the healthy subjects. Based on Fast UniFrac analysis, distinctive bacterial clusters were classified for the healthy, gingivitis, and periodontitis state. The current findings might be useful for understanding the pathogenesis, diagnosis, and treatment of periodontal diseases.
Sintering is the process of forming materials and components from a powder under the action of thermal energy. It is a key materials science subject; most ceramic materials and many specialist metal ...powder products for use in key industries such as electronics, automotive and aerospace are formed this way. Written by one of the leading experts in the field, this book offers an unrivalled introduction to sintering and sintering processes for students of materials science and engineering, and practicing engineers in industry. The book is unique in providing a complete grounding in the principles of sintering and equal coverage of the three key sintering processes: densification, grain growth and microstructure. Students and professional engineers alike will be attracted by the emphasis on developing a detailed understanding of the theory and practical processes of sintering, the balanced coverage of ceramic and metal sintering, and the accompanying examination questions with selected solutions.
Patients with advanced esophageal cancer have a poor prognosis and limited treatment options after first-line chemotherapy.
In this open-label, phase III study, we randomly assigned (1:1) 628 ...patients with advanced/metastatic squamous cell carcinoma or adenocarcinoma of the esophagus, that progressed after one prior therapy, to pembrolizumab 200 mg every 3 weeks for up to 2 years or chemotherapy (investigator's choice of paclitaxel, docetaxel, or irinotecan). Primary end points were overall survival (OS) in patients with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 10, in patients with squamous cell carcinoma, and in all patients (one-sided α 0.9%, 0.8%, and 0.8%, respectively).
At final analysis, conducted 16 months after the last patient was randomly assigned, OS was prolonged with pembrolizumab versus chemotherapy for patients with CPS ≥ 10 (median, 9.3
6.7 months; hazard ratio HR, 0.69 95% CI, 0.52 to 0.93;
= .0074). Estimated 12-month OS rate was 43% (95% CI, 33.5% to 52.1%) with pembrolizumab versus 20% (95% CI, 13.5% to 28.3%) with chemotherapy. Median OS was 8.2 months versus 7.1 months (HR, 0.78 95% CI, 0.63 to 0.96;
= .0095) in patients with squamous cell carcinoma and 7.1 months versus 7.1 months (HR, 0.89 95% CI, 0.75 to 1.05;
= .0560) in all patients. Grade 3-5 treatment-related adverse events occurred in 18.2% of patients with pembrolizumab versus 40.9% in those who underwent chemotherapy.
Pembrolizumab prolonged OS versus chemotherapy as second-line therapy for advanced esophageal cancer in patients with PD-L1 CPS ≥ 10, with fewer treatment-related adverse events.
Regulatory T cells (Tregs) are essential for the establishment and maintenance of immune tolerance, suggesting a potential therapeutic role for Tregs in transplantation. However, Treg administration ...alone is insufficient in inducing long‐term allograft survival in normal hosts, likely due to the high frequency of alloreactive T cells. We hypothesized that a targeted reduction of alloreactive T effector cells would allow a therapeutic window for Treg efficacy. Here we show that preconditioning recipient mice with donor‐specific transfusion followed by cyclophosphamide treatment deleted 70–80% donor‐reactive T cells, but failed to prolong islet allograft survival. However, infusion of either 5 × 106 Tregs with direct donor reactivity or 25 × 106 polyclonal Tregs led to indefinite survival of BALB/c islets in more than 70% of preconditioned C57BL/6 recipients. Notably, protection of C3H islets in autoimmune nonobese diabetic mice required islet autoantigen‐specific Tregs together with polyclonal Tregs. Treg therapy led to significant reduction of CD8+ T cells and concomitant increase in endogenous Tregs among graft‐infiltrating cells early after transplantation. Together, these results demonstrate that reduction of the donor‐reactive T cells will be an important component of Treg‐based therapies in transplantation.
This study demonstrates that donor‐reactive regulatory T cells are more potent than polyclonal regulatory T cells in preventing rejection; however, both types require depletion of donor‐reactive T effector cells for optimal efficacy. See editorial by Bradley on page 5.
WHO grade II gliomas are divided into three classes:
-wildtype,
-mutant and no 1p/19q codeletion, and
-mutant and 1p/19q-codeleted. Different molecular subtypes have been reported to have prognostic ...differences and different chemosensitivity. Our aim was to evaluate the predictive value of imaging phenotypes assessed with the Visually AcceSAble Rembrandt Images lexicon for molecular classification of lower grade gliomas.
MR imaging scans of 175 patients with lower grade gliomas with known
mutation and 1p/19q-codeletion status were included (78 grade II and 97 grade III) in the discovery set. MR imaging features were reviewed by using Visually AcceSAble Rembrandt Images (VASARI); their associations with molecular markers were assessed. The predictive power of imaging features for
-wild type tumors was evaluated using the Least Absolute Shrinkage and Selection Operator. We tested the model in a validation set (40 subjects).
Various imaging features were significantly different according to
mutation. Nonlobar location, larger proportion of enhancing tumors, multifocal/multicentric distribution, and poor definition of nonenhancing margins were independent predictors of an
wild type according to the Least Absolute Shrinkage and Selection Operator. The areas under the curve for the prediction model were 0.859 and 0.778 in the discovery and validation sets, respectively. The
-mutant, 1p/19q-codeleted group frequently had mixed/restricted diffusion characteristics and showed more pial invasion compared with the
-mutant, no codeletion group.
Preoperative MR imaging phenotypes are different according to the molecular markers of lower grade gliomas, and they may be helpful in predicting the
mutation status.
The economic and man-made resources that sustain human wellbeing are not distributed evenly across the world, but are instead heavily concentrated in cities. Poor access to opportunities and services ...offered by urban centres (a function of distance, transport infrastructure, and the spatial distribution of cities) is a major barrier to improved livelihoods and overall development. Advancing accessibility worldwide underpins the equity agenda of 'leaving no one behind' established by the Sustainable Development Goals of the United Nations. This has renewed international efforts to accurately measure accessibility and generate a metric that can inform the design and implementation of development policies. The only previous attempt to reliably map accessibility worldwide, which was published nearly a decade ago, predated the baseline for the Sustainable Development Goals and excluded the recent expansion in infrastructure networks, particularly in lower-resource settings. In parallel, new data sources provided by Open Street Map and Google now capture transportation networks with unprecedented detail and precision. Here we develop and validate a map that quantifies travel time to cities for 2015 at a spatial resolution of approximately one by one kilometre by integrating ten global-scale surfaces that characterize factors affecting human movement rates and 13,840 high-density urban centres within an established geospatial-modelling framework. Our results highlight disparities in accessibility relative to wealth as 50.9% of individuals living in low-income settings (concentrated in sub-Saharan Africa) reside within an hour of a city compared to 90.7% of individuals in high-income settings. By further triangulating this map against socioeconomic datasets, we demonstrate how access to urban centres stratifies the economic, educational, and health status of humanity.
Hydrographic data collected from research cruises, bottom‐anchored moorings, drifting Ice‐Tethered Profilers, and satellite altimetry in the Beaufort Gyre region of the Arctic Ocean document an ...increase of more than 6,400 km3 of liquid freshwater content from 2003 to 2018: a 40% growth relative to the climatology of the 1970s. This fresh water accumulation is shown to result from persistent anticyclonic atmospheric wind forcing (1997–2018) accompanied by sea ice melt, a wind‐forced redirection of Mackenzie River discharge from predominantly eastward to westward flow, and a contribution of low salinity waters of Pacific Ocean origin via Bering Strait. Despite significant uncertainties in the different observations, this study has demonstrated the synergistic value of having multiple diverse datasets to obtain a more comprehensive understanding of Beaufort Gyre freshwater content variability. For example, Beaufort Gyre Observational System (BGOS) surveys clearly show the interannual increase in freshwater content, but without satellite or Ice‐Tethered Profiler measurements, it is not possible to resolve the seasonal cycle of freshwater content, which in fact is larger than the year‐to‐year variability, or the more subtle interannual variations.
Plain Language
The Beaufort Gyre centered in the Canada Basin of the Arctic Ocean is the major reservoir of fresh water in the Arctic. The primary focus of this study is on quantifying variability and trends in liquid (water) and solid (sea ice) freshwater content in this region. The Beaufort Gyre Exploration Program was initiated in 2003 to synthesize results of historical data analysis, design and conduct long‐term observations, and to provide information for numerical modeling under the umbrella of the FAMOS (Forum for Arctic Observing and Modeling Synthesis) project. The data collected from research cruises, moorings, Ice‐Tethered Profiler observations, and satellite altimetry document an increase of more than 6,400 km3 of liquid freshwater content from 2003 to 2018, a 40% growth relative to the climatology of the 1970s. This fresh water volume is comparable to the fresh water volume released to the sub‐arctic seas during the Great Salinity Anomaly episode of the 1970s. Thus, since the 2000s, the stage has been set for another possible release of fresh water to lower latitudes with accompanying climate impacts, including changes to sea ice conditions, ocean circulation, and ecosystems of the Sub‐Arctic similar to the influence of the Great Salinity Anomaly observed in the 1970s.
Key Points
Beaufort Gyre freshwater content time series (2003–2018) from different data sets are updated, compared, and analyzed
Qualitative and quantitative estimates of factors and mechanisms driving freshwater content changes are provided
In 2003–2018, the major sources of accumulated fresh water were sea ice melt, Mackenzie River runoff, and Bering Strait transport
Two common general anaesthetic methods are total i.v. anaesthesia (TIVA) and inhalation anaesthesia, but it is unclear whether this affects the patient's perception of their quality of recovery. The ...Quality of Recovery-40 questionnaire (QoR-40) is a valid and reliable method to evaluate the extent of functional recovery after surgery with general anaesthesia. This study therefore compared patient recovery using the QoR-40 in surgical patients who received TIVA with those who received desflurane anaesthesia.
Eighty females (20–65 years old) undergoing thyroid surgery were prospectively recruited and randomized to either the TIVA (effect-site target controlled infusion using propofol and remifentanil) or DES (desflurane inhalation with manual infusion of remifentanil) groups. The QoR-40 was administered by an investigator blind to group allocation before surgery, and postoperative days 1 and 2 (POD1 and POD2). Additional data including the incidence of nausea or vomiting, the consumption of antiemetic and analgesic agents in the post-anaesthesia care unit, and the duration of the hospital stay, were collected in all cases.
The QoR-40 score on POD1 was significantly higher in the TIVA group compared with the DES group (174 vs 161, respectively; P=0.004), indicating a better quality of recovery in the TIVA group. Among the five dimensions of the QoR-40, physical comfort and physical independence were significantly better on POD1 and POD2 in the TIVA group.
This study demonstrates that the quality of recovery for female thyroid surgery patients is significantly better with TIVA compared with desflurane anaesthesia.
www.clinicaltrials.org; ref.: NCT01760018.
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