In this article, a dataset from a collaborative non-target screening trial organised by the NORMAN Association is used to review the state-of-the-art and discuss future perspectives of non-target ...screening using high-resolution mass spectrometry in water analysis. A total of 18 institutes from 12 European countries analysed an extract of the same water sample collected from the River Danube with either one or both of liquid and gas chromatography coupled with mass spectrometry detection. This article focuses mainly on the use of high resolution screening techniques with target, suspect, and non-target workflows to identify substances in environmental samples. Specific examples are given to emphasise major challenges including isobaric and co-eluting substances, dependence on target and suspect lists, formula assignment, the use of retention information, and the confidence of identification. Approaches and methods applicable to unit resolution data are also discussed. Although most substances were identified using high resolution data with target and suspect-screening approaches, some participants proposed tentative non-target identifications. This comprehensive dataset revealed that non-target analytical techniques are already substantially harmonised between the participants, but the data processing remains time-consuming. Although the objective of a “fully-automated identification workflow” remains elusive in the short term, important steps in this direction have been taken, exemplified by the growing popularity of suspect screening approaches. Major recommendations to improve non-target screening include better integration and connection of desired features into software packages, the exchange of target and suspect lists, and the contribution of more spectra from standard substances into (openly accessible) databases.
Graphical Abstract
Matrix of identification approach versus identification confidence
Frozen shoulder (FS) is a common cause of shoulder pain and stiffness. Conservative treatment is sufficient for the majority of patients with long-term recovery of shoulder function. Manipulation ...under anesthesia (MUA) is known as a well-established treatment option if conservative treatment fails. It is unknown whether MUA does indeed shorten the duration of symptoms or leads to a superior outcome compared to conservative treatment. The objective of the current trial is to evaluate the effectiveness of MUA followed by a physiotherapy (PT) program compared to a PT program alone in patients with stage 2 FS.
A prospective, single-center randomized controlled trial was performed. Patients between 18 and 70 years old with stage 2 FS were deemed eligible if an initial course of conservative treatment consisting of PT and intra-articular corticosteroid infiltration was considered unsatisfactory. Patients were randomized, and data was collected with an online data management platform (CASTOR). MUA was performed by a single surgeon under interscalene block, and intensive PT treatment protocol was started within 4 hours after MUA. In the PT group, patients were referred to instructed physiotherapist, and treatment was guided by tissue irritability. The primary outcome was the Shoulder Pain and Disability Index (SPADI) score. Secondary outcomes were pain, range of motion (ROM), Oxford Shoulder Score, quality of life, and ability to work.
In total, 82 patients were included, 42 in the PT group and 40 in the MUA group. There was a significant improvement in SPADI, Oxford Shoulder Score, pain, ROM, and quality of life in both groups at 1-year follow-up. SPADI scores at three months were significantly improved in favor of MUA. MUA showed a significantly bigger increase in anteflexion and abduction compared to PT at all points of follow-up. No significant differences between both groups were found for all other parameters. No fractures, dislocations, or brachial plexus injuries occurred in this trial.
MUA in stage 2 FS can be considered safe and results in a faster recovery of ROM and improved functional outcome, measured with SPADI scores, compared to PT alone in the short term. After 1 year, except for slightly better ROM scores for MUA, the result of MUA is equal to PT.
Effect-directed analysis has been applied to a river sediment sample of concern to identify the compounds responsible for the observed effects in an in vitro (anti-)androgenicity assay. For ...identification after non-target analysis performed on a high-resolution LTQ-Orbitrap, we developed a de novo identification strategy including physico-chemical parameters derived from the effect-directed analysis approach. With this identification strategy, we were able to handle the immense amount of data produced by non-target accurate mass analysis. The effect-directed analysis approach, together with the identification strategy, led to the successful identification of eight androgen-disrupting compounds belonging to very diverse compound classes: an oxygenated polyaromatic hydrocarbon, organophosphates, musks, and steroids. This is one of the first studies in the field of environmental analysis dealing with the difficult task of handling the large amount of data produced from non-target analysis. The combination of bioassay activity assessment, accurate mass measurement, and the identification and confirmation strategy is a promising approach for future identification of environmental key toxicants that are not included as priority pollutants in monitoring programs.
The uncertainty and financial instability that has plagued companies and industries in the last decade is one of the root causes behind the development of Supply Chain Finance (SCF), a set of schemes ...aiming to optimise the management of financial flows at the supply chain level. Recent years have seen a proliferation of different SCF schemes, with different impacts on working capital costs and requirements throughout the supply chain. The practicality of SCF usage indicates that the concurrent adoption of multiple schemes is not only possible, but even likely. However, literature on SCF still focuses on individual SCF schemes, while the concurrent adoption of multiple SCF schemes remains largely unaddressed. Thus, the objective of this paper is to assess the tangible benefits deriving from a multi-scheme SCF strategy. Based on the analytical formulation of the benefits of three relevant SCF schemes (Reverse Factoring, Inventory Financing and Dynamic Discounting), the paper formalises a model that investigates the benefits that a buyer can achieve by onboarding suppliers onto these three schemes. The results show how working capital requirements and the cost of finance represent the key parameters to assessing the benefits of the concurrent adoption of multiple SCF schemes. Moreover, the funding limits of the SCF schemes themselves strongly affect the relevance of such strategies; strict limits will increase the relevance of having ‘alternative’ schemes available to onboard suppliers. To highlight the managerial relevance of the model, the article provides a numerical example based on a real-world application.
•Concurrent adoption of multiple Supply Chain Finance schemes is becoming common among practitioners.•Concurrent adoption of multiple SCF scheme has potential to lead to higher overall tangible benefits for the adopting buyer.•Parameters affecting such benefits are working capital costs and requirements within the supply base, as well as scheme-dependent funding limits.
With supply chain finance gaining more prominence in practice and drawing increasing attention from researchers, the question arises how this emerging discipline can build on existing theoretical ...conceptualisations. However, few studies have incorporated theoretical frameworks and there remains therefore a gap in literature. To fill this gap, the study reviews five theories on their suitability for supply chain finance: transaction cost economics, agency theory, network theory, collaborative networks and social exchange theory. A Scottish focus group consisting of practitioners involved in supply chain finance provided empirical data for the evaluation. The findings suggest that there is supporting evidence for using agency theory, network theory, transaction cost economics and social exchange theory as theoretical frameworks for studying phenomena of supply chain finance. Furthermore, the results indicate that the conceptualisations based on agency theory should be extended with ‘reverse principal–agent theory’ to fit with the contingencies of supply chain finance. The frameworks of collaborative networks are found less suitable. In addition to these theoretical considerations, the focus group discussion also points out that the financial department's collaboration with other departments involved in the primary supply chain process in firms needs to be improved. To achieve this training and supplier development, particularly for smaller firms, is seen as key. These outcomes have informed a research agenda for research groups, early career researchers and doctoral students.
•Uses focus group for delineating relevant theories to supply chain finance.•Evidence for network theory, transaction cost economics and social exchange theory.•Evidence on agency theory includes reverse principal-agent relationships.•Theory for collaborative networks less appropriate, except game theory.•Intra-firm collaboration with financial departments needs to be bolstered.
A novel low-melting, low-viscosity, one-part bismaleimide resin based on m-xylylene bismaleimide has been developed and examined for application in vacuum-assisted resin infusion. The resin is a ...fully formulated system comprising a ternary eutectic BMI mixture blended with bis-(o-propenylphenoxy)benzophenone and 2,2'-bis(3-allyl-4-hydroxyphenyl)propane as co-monomers. The resin offers enhanced properties for melt processing techniques. The formulation strategy and chemistry is presented and discussed in detail. For resin infusion and/or resin transfer molding technologies, the melt processing temperature of the resin is in the range of 90–110℃. Processing data of the uncured and mechanical properties of cured neat resin are provided. The resin shows a Tgof 285℃ when post-cured at 250℃ for 6 h. Finally, a 400 × 500 mm2carbon fabric laminate was successfully molded for demonstration by a VARI process. The microscopic study reveals no voids and no laminate surface imperfections. The VARI processing details are presented and discussed.
The protein substrates of sirtuin 5-regulated lysine malonylation (Kmal) remain unknown, hindering its functional analysis. In this study, we carried out proteomic screening, which identified 4042 ...Kmal sites on 1426 proteins in mouse liver and 4943 Kmal sites on 1822 proteins in human fibroblasts. Increased malonyl-CoA levels in malonyl-CoA decarboxylase (MCD)-deficient cells induces Kmal levels in substrate proteins. We identified 461 Kmal sites showing more than a 2-fold increase in response to MCD deficiency as well as 1452 Kmal sites detected only in MCD−/− fibroblast but not MCD+/+ cells, suggesting a pathogenic role of Kmal in MCD deficiency. Cells with increased lysine malonylation displayed impaired mitochondrial function and fatty acid oxidation, suggesting that lysine malonylation plays a role in pathophysiology of malonic aciduria. Our study establishes an association between Kmal and a genetic disease and offers a rich resource for elucidating the contribution of the Kmal pathway and malonyl-CoA to cellular physiology and human diseases.
Inherited disorders of acyl-CoA metabolism, such as defects in amino acid metabolism and fatty acid oxidation can present with severe clinical symptoms either neonatally or later in life, but the ...pathophysiological mechanisms are often incompletely understood. We now report the discovery of a novel biochemical mechanism that could contribute to the pathophysiology of these disorders. We identified increased protein lysine butyrylation in short-chain acyl-CoA dehydrogenase (SCAD) deficient mice as a result of the accumulation of butyryl-CoA. Similarly, in SCAD deficient fibroblasts, lysine butyrylation was increased. Furthermore, malonyl-CoA decarboxylase (MCD) deficient patient cells had increased levels of malonylated lysines and propionyl-CoA carboxylase (PCC) deficient patient cells had increased propionylation of lysines. Since lysine acylation can greatly impact protein function, aberrant lysine acylation in inherited disorders associated with acyl-CoA accumulation may well play a role in their disease pathophysiology.
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