Cyanobacteria and their secondary metabolites in three freshwater reservoirs in the United Kingdom

Background Bloom-forming cyanobacteria occur globally in aquatic environments. They produce diverse bioactive metabolites, some of which are known to be toxic. The most studied cyanobacterial toxins are microcystins, anatoxin, and cylindrospermopsin, yet more than 2000 bioactive metabolites have been identified to date. Data on the occurrence of cyanopeptides other than microcystins in surface waters are sparse. Results We used a high-performance liquid chromatography-high-resolution mass spectrometry/tandem mass spectrometry (HPLC-HRMS/MS) method to analyse cyanotoxin and cyanopeptide profiles in raw drinking water collected from three freshwater reservoirs in the United Kingdom. A total of 8 cyanopeptides were identified and quantified using reference standards. A further 20 cyanopeptides were identified based on a suspect-screening procedure, with class-equivalent quantification. Samples from Ingbirchworth reservoir showed the highest total cyanopeptide concentrations, reaching 5.8, 61, and 0.8 µg/L in August, September, and October, respectively. Several classes of cyanopeptides were identified with anabaenopeptins, cyanopeptolins, and microcystins dominating in September with 37%, 36%, and 26%, respectively. Samples from Tophill Low reservoir reached 2.4 µg/L in September, but remained below 0.2 µg/L in other months. Samples from Embsay reservoir did not exceed 0.1 µg/L. At Ingbirchworth and Tophill Low, the maximum chlorophyll-a concentrations of 37 µg/L and 22 µg/L, respectively, and cyanobacterial count of 6 × 10 cells/mL were observed at, or a few days after, peak cyanopeptide concentrations. These values exceed the World Health Organization's guideline levels for relatively low probability of adverse health effects, which are defined as 10 µg/L chlorophyll-a and 2 × 10 cells/mL. Conclusions This data is the first to present concentrations of anabaenopeptins, cyanopeptolins, aeruginosins, and microginins, along with icrocystins, in U.K. reservoirs. A better understanding of those cyanopeptides that are abundant in drinking water reservoirs can inform future monitoring and studies on abatement efficiency during water treatment

Magnitude and Mechanism of Siderophore-Mediated Competition at Low Iron Solubility in the Pseudomonas aeruginosa Pyochelin System

A central question in microbial ecology is whether microbial interactions are predominantly cooperative or competitive. The secretion of siderophores, microbial iron chelators, is a model system for cooperative interactions. However, siderophores have also been shown to mediate competition by sequestering available iron and making it unavailable to competitors. The details of how siderophores mediate competition are not well understood, especially considering the complex distribution of iron phases in the environment. One pertinent question is whether sequestering iron through siderophores can indeed be effective in natural conditions; many natural environments are characterized by large pools of precipitated iron, and it is conceivable that any soluble iron that is sequestered by siderophores is replenished by the dissolution of these precipitated iron sources. Our goal here was to address this issue, and investigate the magnitude and mechanism of siderophore-mediated competition in the presence of precipitated iron. We combined experimental work with thermodynamic modeling, using Pseudomonas aeruginosa as a model system and ferrihydrite precipitates as the iron source with low solubility. Our experiments show that competitive growth inhibition by the siderophore pyochelin is indeed efficient, and that inhibition of a competitor can even have a stronger growth-promoting effect than solubilization of precipitated iron. Based on the results of our thermodynamic models we conclude that the observed inhibition of a competitor is effective because sequestered iron is only very slowly replenished by the dissolution of precipitated iron. Our research highlights the importance of competitive benefits mediated by siderophores, and underlines that the dynamics of siderophore production and uptake in environmental communities could be a signature of competitive, not just cooperative, dynamics

Stage III Non-Small Cell Lung Cancer in the elderly: Patient characteristics predictive for tolerance and survival of chemoradiation in daily clinical practice

Background: In unselected elderly with stage III Non-Small Cell Lung Cancer (NSCLC), evidence is scarce regarding motives and effects of treatment modalities. Methods: Hospital-based multicenter retrospective study including unresectable stage III NSCLC patients aged >= 70 and diagnosed between 2009 and 2013 (N = 216). Treatment motives and tolerance (no unplanned hospitalizations and completion of treatment), and survival were derived from medical records and the Netherlands Cancer Registry. Results: Patients received concurrent chemoradiation (cCHRT, 33%), sequential chemoradiation (sCHRT, 24%), radical radiotherapy (RT, 16%) or no curative treatment (27%). Comorbidity, performance status (58%) and patient refusal (15%) were the most common motives for omitting cCHRT. Treatment tolerance for cCHRT and sCHRT was worse in case of severe comorbidity (OR 6.2 (95%Cl 1.6-24) and OR 6.4 (95%CI 1.8-22), respectively). One-year survival was 57%, 50%, 49% and 26% for cCHRT, sCHRT, RT and no curative treatment, respectively. Compared to cCHRT, survival was worse for no curative treatment (P = 0.000), but not significantly worse for sCHRT and RT (P = 0.38). Conclusion: Although relatively fit elderly were assigned to cCHRT, treatment tolerance was worse, especially for those with severe comorbidity. Survival seemed not significantly better as compared to sCHRT or RT. Prospective studies in this vital and understudied area are needed

Response of Submerged Macrophyte Communities to External and Internal Restoration Measures in North Temperate Shallow Lakes

Submerged macrophytes play a key role in north temperate shallow lakes by stabilising clear-water conditions. Eutrophication has resulted in macrophyte loss and shifts to turbid conditions in many lakes. Considerable efforts have been devoted to shallow lake restoration in many countries, but long-term success depends on a stable recovery of submerged macrophytes. However, recovery patterns vary widely and remain to be fully understood. We hypothesize that reduced external nutrient loading leads to an intermediate recovery state with clear spring and turbid summer conditions similar to the pattern described for eutrophication. In contrast, lake internal restoration measures can result in transient clear-water conditions both in spring and summer and reversals to turbid conditions. Furthermore, we hypothesize that these contrasting restoration measures result in different macrophyte species composition, with added implications for seasonal dynamics due to differences in plant traits. To test these hypotheses, we analysed data on water quality and submerged macrophytes from 49 north temperate shallow lakes that were in a turbid state and subjected to restoration measures. To study the dynamics of macrophytes during nutrient load reduction, we adapted the ecosystem model PCLake. Our survey and model simulations revealed the existence of an intermediate recovery state upon reduced external nutrient loading, characterised by spring clear-water phases and turbid summers, whereas internal lake restoration measures often resulted in clear-water conditions in spring and summer with returns to turbid conditions after some years. External and internal lake restoration measures resulted in different macrophyte communities. The intermediate recovery state following reduced nutrient loading is characterised by a few macrophyte species (mainly pondweeds) that can resist wave action allowing survival in shallow areas, germinate early in spring, have energy-rich vegetative propagules facilitating rapid initial growth and that can complete their life cycle by early summer. Later in the growing season these plants are, according to our simulations, outcompeted by periphyton, leading to late-summer phytoplankton blooms. Internal lake restoration measures often coincide with a rapid but transient colonisation by hornworts, waterweeds or charophytes. Stable clear-water conditions and a diverse macrophyte flora only occurred decades after external nutrient load reduction or when measures were combined.Additional co-authors: Wolf M. Mooij, Ruurd Noordhuis, Geoff Phillips, Jacqueline Rücker, Hans-Heinrich Schuster, Martin Søndergaard, Sven Teurlincx, Klaus van de Weyer, Ellen van Donk, Arno Waterstraat and Carl D. Saye

The Natural Products Atlas 2.0 : a database of microbially-derived natural products

Within the natural products field there is an increasing emphasis on the study of compounds from microbial sources. This has been fuelled by interest in the central role that microorganisms play in mediating both interspecies interactions and host-microbe relationships. To support the study of natural products chemistry produced by microorganisms we released the Natural Products Atlas, a database of known microbial natural products structures, in 2019. This paper reports the release of a new version of the database which includes a full RESTful application programming interface (API), a new website framework, and an expanded database that includes 8128 new compounds, bringing the total to 32 552. In addition to these structural and content changes we have added full taxonomic descriptions for all microbial taxa and have added chemical ontology terms from both NP Classifier and ClassyFire. We have also performed manual curation to review all entries with incomplete configurational assignments and have integrated data from external resources, including CyanoMetDB. Finally, we have improved the user experience by updating the Overview dashboard and creating a dashboard for taxonomic origin. The database can be accessed via the new interactive website at https://www.npatlas.org.Peer reviewe

Validation of the Comprehensive Feeding Practices Questionnaire with parents of 10-to-12-year-olds

Abstract Background: There is a lack of validated instruments for quantifying feeding behavior among parents of older children and adolescents. The Comprehensive Feeding Practices Questionnaire (CFPQ) is a self-report measure to assess multiple parental feeding practices. The CFPQ is originally designed for use with parents of children ranging in age from about 2 to 8 years. It is previously validated with American and French parents of children within this age range. The aim of the present study was to adapt and test the validity of this measure with parents of older children (10-to-12-year-olds) in a Norwegian setting. Methods: A sample of 963 parents of 10-to-12-year-olds completed a Norwegian, slightly adapted version of the CFPQ. Scale analyses were performed to test the validity of the instrument in our sample. Results: Although a few problematic items and scales were revealed, scale analyses showed that the psychometric properties of the slightly adapted, Norwegian version of the CFPQ were surprisingly similar to those of the original CFPQ. Conclusions: Our results indicated that the CFPQ, with some small modifications, is a valid tool for measuring multiple parental feeding practices with parents of 10-to12-year-olds

The European construction social partners: gender equality in theory and practice

This article explores the social partners' role in the gender equality agenda in construction at skilled operative level. It draws on a survey of the European construction social partners that investigated the presence of women in skilled trades and the policies, collective agreements and practices that play a role in women's integration. The responses indicate that the construction industry still displays inertia and conservatism, and that the social partners corroborate rather than counter this. They express a 'discourse' of gender equality, but this does not automatically lead to equal opportunity policies or programmes. The social partners have the platform to make inroads and to change the industry from within, but need further encouragement to put this on their agenda

2 days versus 5 days of postoperative antibiotics for complex appendicitis:a pragmatic, open-label, multicentre, non-inferiority randomised trial

Background: The appropriate duration of postoperative antibiotics for complex appendicitis is unclear. The increasing global threat of antimicrobial resistance warrants restrictive antibiotic use, which could also reduce side-effects, length of hospital stay, and costs. Methods: In this pragmatic, open-label, non-inferiority trial in 15 hospitals in the Netherlands, patients with complex appendicitis (aged ≥8 years) were randomly assigned (1:1) to receive 2 days or 5 days of intravenous antibiotics after appendicectomy. Randomisation was stratified by centre, and treating physicians and patients were not masked to treatment allocation. The primary endpoint was a composite endpoint of infectious complications and mortality within 90 days. The main outcome was the absolute risk difference (95% CI) in the primary endpoint, adjusted for age and severity of appendicitis, with a non-inferiority margin of 7·5%. Outcome assessment was based on electronic patient records and a telephone consultation 90 days after appendicectomy. Efficacy was analysed in the intention-to-treat and per-protocol populations. Safety outcomes were analysed in the intention-to-treat population. This trial was registered with the Netherlands Trial Register, NL5946. Findings: Between April 12, 2017, and June 3, 2021, 13 267 patients were screened and 1066 were randomly assigned, 533 to each group. 31 were excluded from intention-to-treat analysis of the 2-day group and 30 from the 5-day group owing to errors in recruitment or consent. Appendicectomy was done laparoscopically in 955 (95%) of 1005 patients. The telephone follow-up was completed in 664 (66%) of 1005 patients. The primary endpoint occurred in 51 (10%) of 502 patients analysed in the 2-day group and 41 (8%) of 503 patients analysed in the 5-day group (adjusted absolute risk difference 2·0%, 95% CI −1·6 to 5·6). Rates of complications and re-interventions were similar between trial groups. Fewer patients had adverse effects of antibiotics in the 2-day group (45 [9%] of 502 patients) than in the 5-day group (112 [22%] of 503 patients; odds ratio [OR] 0·344, 95% CI 0·237 to 0·498). Re-admission to hospital was more frequent in the 2-day group (58 [12%] of 502 patients) than in the 5-day group (29 [6%] of 503 patients; OR 2·135, 1·342 to 3·396). There were no treatment-related deaths. Interpretation: 2 days of postoperative intravenous antibiotics for complex appendicitis is non-inferior to 5 days in terms of infectious complications and mortality within 90 days, based on a non-inferiority margin of 7·5%. These findings apply to laparoscopic appendicectomy conducted in a well resourced health-care setting. Adopting this strategy will reduce adverse effects of antibiotics and length of hospital stay. Funding: The Netherlands Organization for Health Research and Development.</p

The NORMAN Suspect List Exchange (NORMAN-SLE): facilitating European and worldwide collaboration on suspect screening in high resolution mass spectrometry

Background: The NORMAN Association (https://www.norman-.network.com/) initiated the NORMAN Suspect List Exchange (NORMAN-SLE; https://www.norman-.network.com/nds/SLE/) in 2015, following the NORMAN collaborative trial on non-target screening of environmental water samples by mass spectrometry. Since then, this exchange of information on chemicals that are expected to occur in the environment, along with the accompanying expert knowledge and references, has become a valuable knowledge base for "suspect screening" lists. The NORMAN-SLE now serves as a FAIR (Findable, Accessible, Interoperable, Reusable) chemical information resource worldwide.Results: The NORMAN-SLE contains 99 separate suspect list collections (as of May 2022) from over 70 contributors around the world, totalling over 100,000 unique substances. The substance classes include per- and polyfluoroalkyl substances (PFAS), pharmaceuticals, pesticides, natural toxins, high production volume substances covered under the European REACH regulation (EC: 1272/2008), priority contaminants of emerging concern (CECs) and regulatory lists from NORMAN partners. Several lists focus on transformation products (TPs) and complex features detected in the environment with various levels of provenance and structural information. Each list is available for separate download. The merged, curated collection is also available as the NORMAN Substance Database (NORMAN SusDat). Both the NORMAN-SLE and NORMAN SusDat are integrated within the NORMAN Database System (NDS). The individual NORMAN-SLE lists receive digital object identifiers (DOIs) and traceable versioning via a Zenodo community (https:// zenodo.org/communities/norman-.sle), with a total of > 40,000 unique views, > 50,000 unique downloads and 40 citations (May 2022). NORMAN-SLE content is progressively integrated into large open chemical databases such as PubChem (https://pubchem.ncbi.nlm.nih.gov/) and the US EPA's CompTox Chemicals Dashboard (https://comptox. epa.gov/dashboard/), enabling further access to these lists, along with the additional functionality and calculated properties these resources offer. PubChem has also integrated significant annotation content from the NORMAN-SLE, including a classification browser (https://pubchem.ncbi.nlm.nih.gov/classification/#hid=101).Conclusions: The NORMAN-SLE offers a specialized service for hosting suspect screening lists of relevance for the environmental community in an open, FAIR manner that allows integration with other major chemical resources. These efforts foster the exchange of information between scientists and regulators, supporting the paradigm shift to the "one substance, one assessment" approach. New submissions are welcome via the contacts provided on the NORMAN-SLE website (https://www.norman-.network.com/nds/SLE/)