African swine fever (ASF) is a highly contagious disease of domestic pigs and wild boars (WBs). Without a vaccine, early antibody and antigen detection and rapid diagnosis are crucial for the ...effective prevention of the disease and the employment of control measures. In Sardinia, where 3 different suid populations coexisted closely for a long time, the disease persists since 1978. The recent ASF eradication plan involves more stringent measures to combat free-ranging pigs and any kind of illegality in the pig industry. However, critical issues such as the low level of hunter cooperation with veterinary services and the time required for ASF detection in the WBs killed during the hunting season still remain. Considering the need to deliver true ASF negative carcasses as early as possible, this study focuses on the evaluation and validation of a duplex pen-side test that simultaneously detects antibodies and antigens specific to ASF virus, to improve molecular diagnosis under field conditions. The main goal was to establish the specificity of the two pen-side tests performed simultaneously and to determine their ability to detect the true ASF negative carcasses among the hunted WBs. Blood and organ samples of the WBs hunted during the 2018/2019 hunting seasons were obtained. A total of 160 animals were tested using the pen-side kit test; samples were collected for virological and serological analyses. A specificity of 98% was observed considering the official laboratory tests as gold standards. The new diagnostic techniques could facilitate faster and cost-effective control of the disease.
ABSTRACT
It is thought that magnetic fields must be present in the interiors of stars to resolve certain discrepancies between theory and observation (e.g. angular momentum transport), but such ...fields are difficult to detect and characterize. Asteroseismology is a powerful technique for inferring the internal structures of stars by measuring their oscillation frequencies, and succeeds particularly with evolved stars, owing to their mixed modes, which are sensitive to the deep interior. The goal of this work is to present a phenomenological study of the combined effects of rotation and magnetism in evolved stars, where both are assumed weak enough that first-order perturbation theory applies, and we focus on the regime where Coriolis and Lorentz forces are comparable. Axisymmetric ‘twisted-torus’ field configurations are used, which are confined to the core and allowed to be misaligned with respect to the rotation axis. Factors such as the field radius, topology and obliquity are examined. We observe that fields with finer-scale radial structure and/or smaller radial extent produce smaller contributions to the frequency shift. The interplay of rotation and magnetism is shown to be complex: we demonstrate that it is possible for nearly symmetric multiplets of apparently low multiplicity to arise even under a substantial field, which might falsely appear to rule out its presence. Our results suggest that proper modelling of rotation and magnetism, in a simultaneous fashion, may be required to draw robust conclusions about the existence/non-existence of a core magnetic field in any given object.
Unresectable locally advanced or metastatic triple-negative (hormone-receptor-negative and human epidermal growth factor receptor 2 HER2-negative) breast cancer is an aggressive disease with poor ...outcomes. Nanoparticle albumin-bound (nab)-paclitaxel may enhance the anticancer activity of atezolizumab.
In this phase 3 trial, we randomly assigned (in a 1:1 ratio) patients with untreated metastatic triple-negative breast cancer to receive atezolizumab plus nab-paclitaxel or placebo plus nab-paclitaxel; patients continued the intervention until disease progression or an unacceptable level of toxic effects occurred. Stratification factors were the receipt or nonreceipt of neoadjuvant or adjuvant taxane therapy, the presence or absence of liver metastases at baseline, and programmed death ligand 1 (PD-L1) expression at baseline (positive vs. negative). The two primary end points were progression-free survival (in the intention-to-treat population and PD-L1-positive subgroup) and overall survival (tested in the intention-to-treat population; if the finding was significant, then it would be tested in the PD-L1-positive subgroup).
Each group included 451 patients (median follow-up, 12.9 months). In the intention-to-treat analysis, the median progression-free survival was 7.2 months with atezolizumab plus nab-paclitaxel, as compared with 5.5 months with placebo plus nab-paclitaxel (hazard ratio for progression or death, 0.80; 95% confidence interval CI, 0.69 to 0.92; P=0.002); among patients with PD-L1-positive tumors, the median progression-free survival was 7.5 months and 5.0 months, respectively (hazard ratio, 0.62; 95% CI, 0.49 to 0.78; P<0.001). In the intention-to-treat analysis, the median overall survival was 21.3 months with atezolizumab plus nab-paclitaxel and 17.6 months with placebo plus nab-paclitaxel (hazard ratio for death, 0.84; 95% CI, 0.69 to 1.02; P=0.08); among patients with PD-L1-positive tumors, the median overall survival was 25.0 months and 15.5 months, respectively (hazard ratio, 0.62; 95% CI, 0.45 to 0.86). No new adverse effects were identified. Adverse events that led to the discontinuation of any agent occurred in 15.9% of the patients who received atezolizumab plus nab-paclitaxel and in 8.2% of those who received placebo plus nab-paclitaxel.
Atezolizumab plus nab-paclitaxel prolonged progression-free survival among patients with metastatic triple-negative breast cancer in both the intention-to-treat population and the PD-L1-positive subgroup. Adverse events were consistent with the known safety profiles of each agent. (Funded by F. Hoffmann-La Roche/Genentech; IMpassion130 ClinicalTrials.gov number, NCT02425891 .).
•Hybrid energy management is adopted for networked microgrids.•Risk control is incorporated by introducing mean–variance Markowitz theory.•Two-stage energy management is proposed to improve control ...accuracy.•Uncertainties existing in the system are fully addressed.
Networking of microgrids has received increasing attentions in recent years, which requires the uncertainty management associated with variations in the system. In this paper, a two-stage energy management strategy is developed for networked microgrids under the presence of high renewable resources. It decomposes the microgrids energy management into two stages to counteract the intra-day stochastic variations of renewable energy resources, electricity load and electricity prices. In the first stage (hourly time scale), a hierarchical hybrid control method is employed for networked microgrids, aiming to minimize the system operation cost. The mean–variance Markowitz theory is employed to assess the risk of operation cost variability due to the presence of uncertainties. In the second stage (5-min time scale), the components in microgrids are optimally adjusted to minimize the imbalance cost between day-ahead and real-time markets. Simulation study is conducted on an uncoordinated microgrids system as well as on the proposed networked system. According to the simulation results, the proposed method can identify optimal scheduling results, reduce operation costs of risk-aversion, and mitigate the impact of uncertainties.
How DNA methylation is interpreted and influences genome regulation remains largely unknown. Proteins of the methyl-CpG-binding domain (MBD) family are primary candidates for the readout of DNA ...methylation as they recruit chromatin remodelers, histone deacetylases and methylases to methylated DNA associated with gene repression. MBD protein binding requires both functional MBD domains and methyl-CpGs; however, some MBD proteins also bind unmethylated DNA and active regulatory regions via alternative regulatory domains or interaction with the nucleosome remodeling deacetylase (NuRD/Mi-2) complex members. Mutations within MBD domains occur in many diseases, including neurological disorders and cancers, leading to loss of MBD binding specificity to methylated sites and gene deregulation. Here, we summarize the current state of knowledge about MBD proteins and their role as readers of the epigenome.
In 2014, we described a method to quantify percentage of tumor-infiltrating lymphocytes (TILs) on hematoxylin and eosin-stained slides of breast cancer samples using light microscopy that could be ...performed easily by pathologists with no extra stains. The aim of detailing the method was to facilitate independent research groups replicating our prognostic findings using TIL quantity in early-stage breast cancers. A global working group of breast pathologists was convened to standardize, test reproducibility, and refine the method. A website was also established which allowed free training (www.tilsinbreastcancer.org). As a result of this work, TIL data have been collected in over 20 000 primary breast cancer samples worldwide and the robust associations with better prognoses in triple-negative breast cancer (TNBC) and HER2+ BC have been confirmed. This has resulted in the inclusion of the TIL biomarker in several international breast cancer guidelines as well as in national criteria for routine pathology reporting. TIL therefore represents the first biological prognostic biomarker for early-stage TNBCs, and here its prognostic effect is linear, with values of 30%-50% being suggested as suitable for use in potential chemotherapy de-escalation studies. The efficacy of immune checkpoint-targeted agents in breast cancer now provides direct evidence that host immune responses can modify tumor growth in some patients. With the recent granting of accelerated approvals for the first PD-1/PD-L1 targeting agents in early and advanced TNBC, our focus has now moved to investigating the clinical utility of TIL in the setting of immune checkpoint agents, with or without PD-L1 protein assessment. Emerging data suggest that TIL quantity can help clinicians identify patients with breast cancer who benefit most from PD-1/PD-L1 inhibition. In patients with advanced TNBC and HER2+ disease a TIL cut-off of 5% or 10%, with PD-L1 expression can define ‘immune-enriched’ tumors and currently seems to have the most clinical relevance in this context.
•TILs is a strong prognostic biomarker in some breast cancer subtypes in early-stage setting.•Our method of quantifying TIL published 5+ years ago has been standardized, is reproducible, and has been adopted worldwide.•TIL quantity has shown to be predictive of benefit from agents targeting PD-1/PD-L1 in the metastatic setting.•TIL quantity correlates with many other immune biomarkers. TIL and PD-L1 expression together can identify ‘immune-rich’ tumors.•Investigating the relevant immune subsets important for prognosis and immunotherapy response is ongoing.
In the paclitaxel group, the proportion of patients who achieved a pathological complete response was nearly 2·5 higher than in those who did not receive paclitaxel.4 However, considering ...anthracyclines' risks of febrile neutropenia, alopecia, cardiac toxicity, and leukaemia, studying whether removal of the anthracycline component is safe but still effective for patients with early-stage HER2-positive breast cancer would seem warranted. In The Lancet Oncology, the phase 3 randomised TRAIN-2 neoadjuvant study asked this question and investigated an anthracycline-free regimen of 27 weeks duration of nine cycles of paclitaxel, carboplatin, trastuzumab, and pertuzumab or an anthracycline-containing regimen of three cycles of standard 5-fluorouracil–epirubicin–cyclophosphamide treatment followed by six cycles of paclitaxel and carboplatin, also with concurrent trastuzumab and pertuzumab.5 Both groups reported nearly identical proportions of patients achieving pathological complete responses: 67% (141 of 212 patients) in the anthracycline group and 68% (140 of 206 patients) in the non-anthracycline group. In countries whose health-care systems can afford this treatment approach, the aim here would be to get as many patients as possible achieving a pathological complete response with the prescription of upfront intensive shutdown of HER2 signalling using trastuzumab with pertuzumab. Because patients who achieve pathological complete response have excellent survival, leaving out the anthracycline component can be justified.
We report on the synthesis and characterization of a new family of palladium–alkali olefin polymerization catalysts using site-differentiated dinucleating platforms. Metal binding studies indicate ...that our palladium phosphine phosphonate polyethylene glycol (PEG) complexes form 1:1 adducts with alkali cations in solution, with relative affinities in the order Na+ ≈ K+ > Li+. We observed that these palladium–alkali complexes are more active for ethylene homopolymerization and ethylene/alkyl acrylate copolymerization in comparison to their monopalladium counterparts, although their effect on polymer branching and molecular weight is relatively modest. In some cases, the addition of external sodium salts to conventional palladium complexes (i.e., those that do not have pendant PEG chains) also led to remarkable catalyst enhancements, presumably also due to the formation of palladium–sodium species. The unique features of our heterobimetallic systems are that they display long catalyst lifetimes at 100 °C and can even operate at temperatures as high as 140 °C. Although we have shown that secondary cations clearly increase the electrophilicity of the metal catalyst, their precise role in these polymerization reactions is still under investigation.
Previously, much of the perfluoroalkyl and polyfluoroalkyl substance (PFAS) research has focused on perfluoroalkyl carboxylates (PFCAs) or perfluoroalkane sulfonates (PFSAs). Recent studies indicate ...that known PFCAs and PFSAs accounted for 5–95% of the organofluorine (OF) in human and wild rat blood samples suggesting that a relatively large proportion of OF remained unknown. Until recently, some studies reported commercially available compounds such as polyfluoroalkyl phosphate diesters (diPAPs) and fluorotelomer sulfonates (FTSAs) in human blood and sludge samples. The present investigation is a pilot study aiming at surveying some newly identified PFASs such as diPAPs, FTSAs, and perfluorinated phosphinates (PFPiAs) in different environmental samples including surface water, sediment, sewage treatment plant influent and effluent, sludge, benthic worm, and human blood from Hong Kong. DiPAPs (6:2, 6:2/8:2, and 8:2) were detected in some of the samples at part-per-billion (ppb) levels in sludge, sub ppb levels in influent and effluent, sediment, worm, and human blood samples, and sub part-per-trillion (ppt) levels in surface waters. Sub ppt to ppb levels of 6:2 and 8:2 FTSAs were observed in worm, surface water, and human blood samples. PFPiAs were only observed in worm samples. The detected “new PFASs” accounted for a minor proportion (less than 5%) of the total PFASs in benthic worm and human blood, but up to 95% in sewage sludge samples from Hong Kong. This is the first report of commercial fluorosurfactants (PFPiAs, diPAPs, and FTSAs) in the samples from the environment and human blood in Hong Kong; further information on the distribution, fate, and transport of “new PFASs” in other Asian cities, as well as toxicity, is needed for further assessing the human exposure and risk.
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