Solvent-Free Preparation of Thermally Stable Poly(urethane-imide) Elastomers

Polyurethanes (PUs) are widely used in many applications due to their versatile chemical and physical properties. To meet the increasing demands on PU with respect to intrinsic mechanical and thermal properties, they can be modified with thermally stable aromatic imide structures to form poly(urethane imide) (PUI). However, the preparation of PUI materials has been limited by the need for strong polar solvents, which hinder their industrial scale development. In this work, we prepared imide-containing isocyanate-terminated prepolymers via the reaction of polymeric aromatic or aliphatic isocyanates and pyromellitic dianhydride in completely solvent-free conditions. The subsequent PUI elastomers made from these prepolymers exhibited enhanced char formation and stiffness in comparison to the reference elastomers without imide structures, among which the aromatic PUI elastomer shows improved flame retardancy according to the initial cone calorimetry measurement. This work demonstrates the potential use of imide prepolymers in other PU applications where high thermal stability and flame retardancy are required. The solvent-free synthesis also paves a way for the large-scale production of PUI materials

Evaluation des Bereichs Forschung und Entwicklung im Bundesprogramm Ökologischer Landbau

In 2010, the BLE commissioned an evaluation of the Federal Organic Farming Scheme (BÖL), running since 2001. This paper reports on the approach taken in the evaluation of its research component, selected findings, and recommendations. An impact model of the BÖL scheme was developed to analyse how the various measures could contribute to the scheme’s overall aims and objectives. Data from the BLE research project database were analysed to assess the distribution of resources over time by topic and by research provider. At project level, a random selection of 83 projects was reviewed by external experts, including both scientists and other stakeholders to assess their quality and relevance. An online survey of 104 project leaders and interviews with 30 sector stakeholders and 12 BLE employees were carried out and the theme identification and project selection processes were analysed to evaluate whether the programme management contribute was in line with programme goals. The overall conclusions of the evaluation were then reviewed by external experts. The evaluation concludes that financed projects resulted in a compendium of easily accessible results. The research is relevant to the sector and this is one of the greatest strengths of the programme. However, the consistently high allocation of resources to crops and soil themes is noted as a weakness. A more strategic approach to the identification of research targets and to the development of impact from research outputs with appropriate measures at both programme and project level is recommended

A genome-wide screen identifies genes that suppress the accumulation of spontaneous mutations in young and aged yeast cells

To ensure proper transmission of genetic information, cells need to preserve and faithfully replicate their genome, and failure to do so leads to genome instability, a hallmark of both cancer and aging. Defects in genes involved in guarding genome stability cause several human progeroid syndromes, and an age-dependent accumulation of mutations has been observed in different organisms, from yeast to mammals. However, it is unclear whether the spontaneous mutation rate changes during aging and whether specific pathways are important for genome maintenance in old cells. We developed a high-throughput replica-pinning approach to screen for genes important to suppress the accumulation of spontaneous mutations during yeast replicative aging. We found 13 known mutation suppression genes, and 31 genes that had no previous link to spontaneous mutagenesis, and all acted independently of age. Importantly, we identified PEX19, encoding an evolutionarily conserved peroxisome biogenesis factor, as an age-specific mutation suppression gene. While wild-type and pex19Δ young cells have similar spontaneous mutation rates, aged cells lacking PEX19 display an elevated mutation rate. This finding suggests that functional peroxisomes may be important to preserve genome integrity specifically in old cells

Risk factors for adverse events induced by immune checkpoint inhibitors in patients with non-small-cell lung cancer:a systematic review and meta-analysis

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause serious immune-related adverse events (irAEs). This study aimed to identify risk factors for all types of irAEs induced by ICIs in patients with non-small-cell lung cancer (NSCLC), by systematic review and meta-analyses. METHODS: A systematic search was performed in Pubmed, Embase and Web of Science by two independent reviewers. Studies were selected that included patients with NSCLC and evaluated characteristics of patients with and without irAEs induced by ICIs. Quality and risk of bias of the selected studies were assessed. Random effects meta-analyses were conducted to estimate pooled odds ratios (ORs) for risk factors of developing all type of irAEs, and separately for pneumonitis, interstitial lung disease and severe irAEs. With the objective of exploring sources of heterogeneity, stratified analyses were performed by quality and region. RESULTS: 25 studies met the inclusion criteria. In total, the data of 6696 patients were pooled. 33 different risk factors for irAEs were reported. irAEs of interest were reported for 1653 (25%) of the patients. Risk factors related to the development of irAEs were: C-reactive protein, neutrophil lymphocyte ratio (NLR), use of PD-1 inhibitor, high PD-L1 expression, an active or former smoking status, ground glass attenuation, and a better treatment response. CONCLUSION: The identified risk factors for the development of these irAEs are mostly related to the alteration of the immune system, proinflammatory states and loss of immunological self-tolerance. Patients identified as having a higher risk for irAEs should be monitored more closely

Sustainable bioenergy for climate mitigation: Developing drought-tolerant trees and grasses

\u2022 Background and Aims Bioenergy crops are central to climate mitigation strategies that utilize biogenic carbon, such as BECCS (bioenergy with carbon capture and storage), alongside the use of biomass for heat, power, liquid fuels and, in the future, biorefining to chemicals. Several promising lignocellulosic crops are emerging that have no food role \u2013 fast-growing trees and grasses \u2013 but are well suited as bioenergy feedstocks, including Populus, Salix, Arundo, Miscanthus, Panicum and Sorghum. \u2022 Scope These promising crops remain largely undomesticated and, until recently, have had limited germplasm resources. In order to avoid competition with food crops for land and nature conservation, it is likely that future bioenergy crops will be grown on marginal land that is not needed for food production and is of poor quality and subject to drought stress. Thus, here we define an ideotype for drought tolerance that will enable biomass production to be maintained in the face of moderate drought stress. This includes traits that can readily be measured in wide populations of several hundred unique genotypes for genome-wide association studies, alongside traits that are informative but can only easily be assessed in limited numbers or training populations that may be more suitable for genomic selection. Phenotyping, not genotyping, is now the major bottleneck for progress, since in all lignocellulosic crops studied extensive use has been made of next-generation sequencing such that several thousand markers are now available and populations are emerging that will enable rapid progress for drought-tolerance breeding. The emergence of novel technologies for targeted genotyping by sequencing are particularly welcome. Genome editing has already been demonstrated for Populus and offers significant potential for rapid deployment of drought-tolerant crops through manipulation of ABA receptors, as demonstrated in Arabidopsis, with other gene targets yet to be tested. \u2022 Conclusions Bioenergy is predicted to be the fastest-developing renewable energy over the coming decade and significant investment over the past decade has been made in developing genomic resources and in collecting wild germplasm from within the natural ranges of several tree and grass crops. Harnessing these resources for climate-resilient crops for the future remains a challenge but one that is likely to be successful

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

Breeding progress and preparedness for mass‐scale deployment of perennial lignocellulosic biomass crops switchgrass, miscanthus, willow and poplar

UK: The UK‐led miscanthus research and breeding was mainly supported by the Biotechnology and Biological Sciences Research Council (BBSRC), Department for Environment, Food and Rural Affairs (Defra), the BBSRC CSP strategic funding grant BB/CSP1730/1, Innovate UK/BBSRC “MUST” BB/N016149/1, CERES Inc. and Terravesta Ltd. through the GIANT‐LINK project (LK0863). Genomic selection and genomewide association study activities were supported by BBSRC grant BB/K01711X/1, the BBSRC strategic programme grant on Energy Grasses & Bio‐refining BBS/E/W/10963A01. The UK‐led willow R&D work reported here was supported by BBSRC (BBS/E/C/00005199, BBS/E/C/00005201, BB/G016216/1, BB/E006833/1, BB/G00580X/1 and BBS/E/C/000I0410), Defra (NF0424) and the Department of Trade and Industry (DTI) (B/W6/00599/00/00). IT: The Brain Gain Program (Rientro dei cervelli) of the Italian Ministry of Education, University, and Research supports Antoine Harfouche. US: Contributions by Gerald Tuskan to this manuscript were supported by the Center for Bioenergy Innovation, a US Department of Energy Bioenergy Research Center supported by the Office of Biological and Environmental Research in the DOE Office of Science, under contract number DE‐AC05‐00OR22725. Willow breeding efforts at Cornell University have been supported by grants from the US Department of Agriculture National Institute of Food and Agriculture. Contributions by the University of Illinois were supported primarily by the DOE Office of Science; Office of Biological and Environmental Research (BER); grant nos. DE‐SC0006634, DE‐SC0012379 and DE‐SC0018420 (Center for Advanced Bioenergy and Bioproducts Innovation); and the Energy Biosciences Institute. EU: We would like to further acknowledge contributions from the EU projects “OPTIMISC” FP7‐289159 on miscanthus and “WATBIO” FP7‐311929 on poplar and miscanthus as well as “GRACE” H2020‐EU.3.2.6. Bio‐based Industries Joint Technology Initiative (BBI‐JTI) Project ID 745012 on miscanthus.Peer reviewedPostprintPublisher PD

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Perennial biomass cropping and use: Shaping the policy ecosystem in European countries

Demand for sustainably produced biomass is expected to increase with the need to provide renewable commodities, improve resource security and reduce greenhouse gas emissions in line with COP26 commitments. Studies have demonstrated additional environmental benefits of using perennial biomass crops (PBCs), when produced appropriately, as a feedstock for the growing bioeconomy, including utilisation for bioenergy (with or without carbon capture and storage). PBCs can potentially contribute to Common Agricultural Policy (CAP) (2023–27) objectives provided they are carefully integrated into farming systems and landscapes. Despite significant research and development (R&D) investment over decades in herbaceous and coppiced woody PBCs, deployment has largely stagnated due to social, economic and policy uncertainties. This paper identifies the challenges in creating policies that are acceptable to all actors. Development will need to be informed by measurement, reporting and verification (MRV) of greenhouse gas emissions reductions and other environmental, economic and social metrics. It discusses interlinked issues that must be considered in the expansion of PBC production: (i) available land; (ii) yield potential; (iii) integration into farming systems; (iv) R&D requirements; (v) utilisation options; and (vi) market systems and the socio-economic environment. It makes policy recommendations that would enable greater PBC deployment: (1) incentivise farmers and land managers through specific policy measures, including carbon pricing, to allocate their less productive and less profitable land for uses which deliver demonstrable greenhouse gas reductions; (2) enable greenhouse gas mitigation markets to develop and offer secure contracts for commercial developers of verifiable low-carbon bioenergy and bioproducts; (3) support innovation in biomass utilisation value chains; and (4) continue long-term, strategic R&D and education for positive environmental, economic and social sustainability impacts