Scale of Emotional Development - Short: reliability and validity in adults with intellectual disability.

BACKGROUND: Intellectual disability (ID) is often associated with delays in emotional development (ED). The Scale of Emotional Development - Short (SED-S) was developed to assess the level of ED and to adapt treatment and care accordingly. METHODS: In a sample of 724 adults from five study sites in three countries, a confirmatory factor analysis with a one-factor model was conducted on the entire dataset as well as in different subgroups. Furthermore, internal consistency was investigated using Cronbach's alpha. RESULTS: The confirmatory factor analysis indicated that a single-factor model fits the SED-S data well. The subgroup analyses revealed good model fit, regardless of the severity of ID and irrespective of sex or the presence of autism spectrum disorder or psychiatric disorders. Internal consistency was excellent for the entire sample (Cronbach's alpha = 0.93) and various subgroups (0.869-0.938). CONCLUSION: The results of this study suggest that the SED-S is psychometrically sound and can be used to assess the level of ED in adults with ID.

Fluorescence grid analysis for the evaluation of piecemeal surgery in sinonasal inverted papilloma: a proof-of-concept study.

PURPOSE: Local recurrence occurs in ~ 19% of sinonasal inverted papilloma (SNIP) surgeries and is strongly associated with incomplete resection. During surgery, it is technically challenging to visualize and resect all SNIP tissue in this anatomically complex area. Proteins that are overexpressed in SNIP, such as vascular endothelial growth factor (VEGF), may serve as a target for fluorescence molecular imaging to guide surgical removal of SNIP. A proof-of-concept study was performed to investigate if the VEGF-targeted near-infrared fluorescent tracer bevacizumab-800CW specifically localizes in SNIP and whether it could be used as a clinical tool to guide SNIP surgery. METHODS: In five patients diagnosed with SNIP, 10 mg of bevacizumab-800CW was intravenously administered 3 days prior to surgery. Fluorescence molecular imaging was performed in vivo during surgery and ex vivo during the processing of the surgical specimen. Fluorescence signals were correlated with final histopathology and VEGF-A immunohistochemistry. We introduced a fluorescence grid analysis to assess the fluorescence signal in individual tissue fragments, due to the nature of the surgical procedure (i.e., piecemeal resection) allowing the detection of small SNIP residues and location of the tracer ex vivo. RESULTS: In all patients, fluorescence signal was detected in vivo during endoscopic SNIP surgery. Using ex vivo fluorescence grid analysis, we were able to correlate bevacizumab-800CW fluorescence of individual tissue fragments with final histopathology. Fluorescence grid analysis showed substantial variability in mean fluorescence intensity (FImean), with SNIP tissue showing a median FImean of 77.54 (IQR 50.47-112.30) compared to 35.99 (IQR 21.48-57.81) in uninvolved tissue (p < 0.0001), although the diagnostic ability was limited with an area under the curve of 0.78. CONCLUSIONS: A fluorescence grid analysis could serve as a valid method to evaluate fluorescence molecular imaging in piecemeal surgeries. As such, although substantial differences were observed in fluorescence intensities, VEGF-A may not be the ideal target for SNIP surgery. TRIAL REGISTRATION: NCT03925285.

Climate change and the permafrost carbon feedback.

Large quantities of organic carbon are stored in frozen soils (permafrost) within Arctic and sub-Arctic regions. A warming climate can induce environmental changes that accelerate the microbial breakdown of organic carbon and the release of the greenhouse gases carbon dioxide and methane. This feedback can accelerate climate change, but the magnitude and timing of greenhouse gas emission from these regions and their impact on climate change remain uncertain. Here we find that current evidence suggests a gradual and prolonged release of greenhouse gas emissions in a warming climate and present a research strategy with which to target poorly understood aspects of permafrost carbon dynamics.

Herbicide Exposure and Toxicity to Aquatic Primary Producers.

The aim of the present review was to give an overview of the current state of science concerning herbicide exposure and toxicity to aquatic primary producers. To this end we assessed the open literature, revealing the widespread presence of (mixtures of) herbicides, inevitably leading to the exposure of non-target primary producers. Yet, herbicide concentrations show strong temporal and spatial variations. Concerning herbicide toxicity, it was concluded that the most sensitive as well as the least sensitive species differed per herbicide and that the observed effect concentrations for some herbicides were rather independent from the exposure time. More extensive ecotoxicity testing is required, especially considering macrophytes and marine herbicide toxicity. Hence, it was concluded that the largest knowledge gap concerns the effects of sediment-associated herbicides on primary producers in the marine/estuarine environment. Generally, there is no actual risk of waterborne herbicides to aquatic primary producers. Still, median concentrations of atrazine and especially of diuron measured in China, the USA and Europe represented moderate risks for primary producers. Maximum concentrations due to misuse and accidents may even cause the exceedance of almost 60% of the effect concentrations plotted in SSDs. Using bioassays to determine the effect of contaminated water and sediment and to identify the herbicides of concern is a promising addition to chemical analysis, especially for the photosynthesis-inhibiting herbicides using photosynthesis as endpoint in the bioassays. This review concluded that to come to a reliable herbicide hazard and risk assessment, an extensive catch-up must be made concerning macrophytes, the marine environment and especially sediment as overlooked and understudied environmental compartments.

Patterns of Growth and Decline in Lung Function in Persistent Childhood Asthma.

BACKGROUND: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction. METHODS: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma. RESULTS: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001). CONCLUSIONS: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

Novel genes and insights in complete asthma remission: A genome-wide association study on clinical and complete asthma remission.

BACKGROUND: Asthma is a chronic respiratory disease without a cure, although there exists spontaneous remission. Genome-wide association (GWA) studies have pinpointed genes associated with asthma development, but did not investigate asthma remission. OBJECTIVE: We performed a GWA study to develop insights in asthma remission. METHODS: Clinical remission (ClinR) was defined by the absence of asthma treatment and wheezing in the last year and asthma attacks in the last 3 years and complete remission (ComR) similarly but additionally with normal lung function and absence of bronchial hyperresponsiveness (BHR). A GWA study on both ClinR and ComR was performed in 790 asthmatics with initial doctor diagnosis of asthma and BHR and long-term follow-up. We assessed replication of the 25 top single nucleotide polymorphisms (SNPs) in 2 independent cohorts (total n = 456), followed by expression quantitative loci (eQTL) analyses of the 4 replicated SNPs in lung tissue and epithelium. RESULTS: Of the 790 asthmatics, 178 (23%) had ClinR and 55 ComR (7%) after median follow-up of 15.5 (range 3.3-47.8) years. In ClinR, 1 of the 25 SNPs, rs2740102, replicated in a meta-analysis of the replication cohorts, which was an eQTL for POLI in lung tissue. In ComR, 3 SNPs replicated in a meta-analysis of the replication cohorts. The top-hit, rs6581895, almost reached genome-wide significance (P-value 4.68 × 10-7 ) and was an eQTL for FRS2 and CCT in lung tissue. Rs1420101 was a cis-eQTL in lung tissue for IL1RL1 and IL18R1 and a trans-eQTL for IL13. CONCLUSIONS AND CLINICAL RELEVANCE: By defining a strict remission phenotype, we identified 3 SNPs to be associated with complete asthma remission, where 2 SNPs have plausible biological relevance in FRS2, CCT, IL1RL1, IL18R1 and IL13.

Activation of old carbon by erosion of coastal and subsea permafrost in Arctic Siberia.

The future trajectory of greenhouse gas concentrations depends on interactions between climate and the biogeosphere. Thawing of Arctic permafrost could release significant amounts of carbon into the atmosphere in this century. Ancient Ice Complex deposits outcropping along the ~7,000-kilometre-long coastline of the East Siberian Arctic Shelf (ESAS), and associated shallow subsea permafrost, are two large pools of permafrost carbon, yet their vulnerabilities towards thawing and decomposition are largely unknown. Recent Arctic warming is stronger than has been predicted by several degrees, and is particularly pronounced over the coastal ESAS region. There is thus a pressing need to improve our understanding of the links between permafrost carbon and climate in this relatively inaccessible region. Here we show that extensive release of carbon from these Ice Complex deposits dominates (57 ± 2 per cent) the sedimentary carbon budget of the ESAS, the world's largest continental shelf, overwhelming the marine and topsoil terrestrial components. Inverse modelling of the dual-carbon isotope composition of organic carbon accumulating in ESAS surface sediments, using Monte Carlo simulations to account for uncertainties, suggests that 44 ± 10 teragrams of old carbon is activated annually from Ice Complex permafrost, an order of magnitude more than has been suggested by previous studies. We estimate that about two-thirds (66 ± 16 per cent) of this old carbon escapes to the atmosphere as carbon dioxide, with the remainder being re-buried in shelf sediments. Thermal collapse and erosion of these carbon-rich Pleistocene coastline and seafloor deposits may accelerate with Arctic amplification of climate warming.

Genes and pathways underlying susceptibility to impaired lung function in the context of environmental tobacco smoke exposure.

BACKGROUND: Studies aiming to assess genetic susceptibility for impaired lung function levels upon exposure to environmental tobacco smoke (ETS) have thus far focused on candidate-genes selected based on a-priori knowledge of potentially relevant biological pathways, such as glutathione S-transferases and ADAM33. By using a hypothesis-free approach, we aimed to identify novel susceptibility loci, and additionally explored biological pathways potentially underlying this susceptibility to impaired lung function in the context of ETS exposure. METHODS: Genome-wide interactions of single nucleotide polymorphism (SNP) by ETS exposure (0 versus ≥1 h/day) in relation to the level of forced expiratory volume in one second (FEV1) were investigated in 10,817 subjects from the Dutch LifeLines cohort study, and verified in subjects from the Swiss SAPALDIA study (n = 1276) and the Dutch Rotterdam Study (n = 1156). SNP-by-ETS exposure p-values obtained from the identification analysis were used to perform a pathway analysis. RESULTS: Fourty Five SNP-by-ETS exposure interactions with p-values <10-4 were identified in the LifeLines study, two being replicated with nominally significant p-values (<0.05) in at least one of the replication cohorts. Three pathways were enriched in the pathway-level analysis performed in the identification cohort LifeLines, i.E. the apoptosis, p38 MAPK and TNF pathways. CONCLUSION: This unique, first genome-wide gene-by-ETS interaction study on the level of FEV1 showed that pathways previously implicated in chronic obstructive pulmonary disease (COPD), a disease characterized by airflow obstruction, may also underlie susceptibility to impaired lung function in the context of ETS exposure.

PTTG1IP and MAML3, novel genomewide association study genes for severity of hyperresponsiveness in adult asthma.

BACKGROUND: The severity of bronchial hyperresponsiveness (BHR) is a fundamental feature of asthma. The severity of BHR varies between asthmatics and is associated with lack of asthma control. The mechanisms underlying this trait are still unclear. This study aimed to identify genes associated with BHR severity, using a genomewide association study (GWAS) on the slope of BHR in adult asthmatics. METHODS: We performed a GWAS on BHR severity in adult asthmatics from the Dutch Asthma GWAS cohort (n = 650), adjusting for smoking and inhaled corticosteroid use, and verified results in three other cohorts. Furthermore, we performed eQTL and co-expression analyses in lung tissue. RESULTS: In the discovery cohort, one genomewide significant hit located in phosphodiesterase 4D, cAMP-specif (PDE4D) and 26 SNPs with P-values < 1*10-5 were found. None of our findings replicated in adult and childhood replication cohorts jointly. In adult cohorts separately, rs1344110 in pituitary tumour-transforming 1 interacting protein (PTTG1IP) and rs345983 in Mastermind-like 3 (MAML3) replicated nominally; minor alleles of rs345983 and rs1344110 were associated with less severe BHR and higher lung tissue gene expression. PTTG1IP showed significant co-expression with pituitary tumour-transforming 1, the binding factor of PTTG1lP, and with vimentin and E-cadherin1. MAML3 co-expressed significantly with Mastermind-like 2 (MAML2), both involved in Notch signalling. CONCLUSIONS: PTTG1IP and MAML3 are associated with BHR severity in adult asthma. The relevance of these genes is supported by the eQTL analyses and co-expression of PTTG1lP with vimentin and E-cadherin1, and MAML3 with MAML2.

Greenhouse Gas Emissions from Reservoir Water Surfaces: A New Global Synthesis.

Collectively, reservoirs created by dams are thought to be an important source of greenhouse gases (GHGs) to the atmosphere. So far, efforts to quantify, model, and manage these emissions have been limited by data availability and inconsistencies in methodological approach. Here, we synthesize reservoir CH4, CO2, and N2O emission data with three main objectives: (1) to generate a global estimate of GHG emissions from reservoirs, (2) to identify the best predictors of these emissions, and (3) to consider the effect of methodology on emission estimates. We estimate that GHG emissions from reservoir water surfaces account for 0.8 (0.5-1.2) Pg CO2 equivalents per year, with the majority of this forcing due to CH4. We then discuss the potential for several alternative pathways such as dam degassing and downstream emissions to contribute significantly to overall emissions. Although prior studies have linked reservoir GHG emissions to reservoir age and latitude, we find that factors related to reservoir productivity are better predictors of emission.

Combining genomewide association study and lung eQTL analysis provides evidence for novel genes associated with asthma.

BACKGROUND: Genomewide association studies (GWASs) of asthma have identified single-nucleotide polymorphisms (SNPs) that modestly increase the risk for asthma. This could be due to phenotypic heterogeneity of asthma. Bronchial hyperresponsiveness (BHR) is a phenotypic hallmark of asthma. We aim to identify susceptibility genes for asthma combined with BHR and analyse the presence of cis-eQTLs among replicated SNPs. Secondly, we compare the genetic association of SNPs previously associated with (doctor's diagnosed) asthma to our GWAS of asthma with BHR. METHODS: A GWAS was performed in 920 asthmatics with BHR and 980 controls. Top SNPs of our GWAS were analysed in four replication cohorts, and lung cis-eQTL analysis was performed on replicated SNPs. We investigated association of SNPs previously associated with asthma in our data. RESULTS: A total of 368 SNPs were followed up for replication. Six SNPs in genes encoding ABI3BP, NAF1, MICA and the 17q21 locus replicated in one or more cohorts, with one locus (17q21) achieving genomewide significance after meta-analysis. Five of 6 replicated SNPs regulated 35 gene transcripts in whole lung. Eight of 20 asthma-associated SNPs from previous GWAS were significantly associated with asthma and BHR. Three SNPs, in IL-33 and GSDMB, showed larger effect sizes in our data compared to published literature. CONCLUSIONS: Combining GWAS with subsequent lung eQTL analysis revealed disease-associated SNPs regulating lung mRNA expression levels of potential new asthma genes. Adding BHR to the asthma definition does not lead to an overall larger genetic effect size than analysing (doctor's diagnosed) asthma.

Long-term exposure to circulating platinum is associated with late effects of treatment in testicular cancer survivors.

BACKGROUND: The success of cisplatin-based (Platinol, Bristol-Myers Squibb Company, New York, NY, USA) chemotherapy for testicular cancer comes at the price of long-term and late effects related to healthy tissue damage. We assessed and modelled serum platinum (Pt) decay after chemotherapy and determined relationships between long-term circulating Pt levels and known late effects. PATIENTS AND METHODS: In 99 testicular cancer survivors, treated with cisplatin-based chemotherapy, serum and 24-h urine samples were collected during follow-up (1-13 years after treatment). To build a population pharmacokinetic model, measured Pt data were simultaneously analysed, together with cisplatin dose, age, weight and height using the NONMEM software. Based on this model, area under the curve between 1 and 3 years after treatment (Pt AUC1-3 years) was calculated for each patient. Predicted long-term Pt exposure was related to renal function and to late effects of treatment assessed median 9 (3-15) years after chemotherapy. RESULTS: Decay of Pt was best described by a two-compartment model. Mean terminal T1/2 was 3.7 (range 2.5-5.2) years. Pt AUC1-3 years correlated with cumulative cisplatin dose, and creatinine clearance before and 1 year after treatment. Patients with paraesthesia had higher Pt AUC1-3 years (30.9 versus 27.0 µg/l month) compared with those without paraesthesia (P = 0.021). Patients with hypogonadism, elevated LDL-cholesterol levels or hypertension also had higher Pt AUC1-3 years. CONCLUSIONS: Renal function before and after cisplatin treatment is an important determinant of long-term Pt exposure. Known long-term effects of testicular cancer treatment, such as paraesthesia, hypogonadism, hypercholesterolaemia and hypertension, are associated with long-term circulating Pt exposure.

Nocturnal non-invasive ventilation in COPD patients with prolonged hypercapnia after ventilatory support for acute respiratory failure: a randomised, controlled, parallel-group study.

INTRODUCTION: The effectiveness of non-invasive positive pressure ventilation (NIV) in COPD patients with prolonged hypercapnia after ventilatory support for acute respiratory failure (ARF) remains unclear. We investigated if nocturnal NIV in these patients prolongs the time to readmission for respiratory causes or death (primary endpoint) in the following 12 months. METHODS: 201 COPD patients admitted to hospital with ARF and prolonged hypercapnia >48 h after termination of ventilatory support were randomised to NIV or standard treatment. Secondary outcomes were daytime arterial blood gasses, transcutaneous PCO2 during the night, lung function, health-related quality-of-life (HRQL), mood state, daily activities and dyspnoea. RESULTS: 1 year after discharge, 65% versus 64% of patients (NIV vs standard treatment) were readmitted to hospital for respiratory causes or had died; time to event was not different (p=0.85). Daytime PaCO2 was significantly improved in NIV versus standard treatment (PaCO2 0.5 kPa (95% CI 0.04 to 0.90, p=0.03)) as was transcutaneous PCO2 during the night. HRQL showed a trend (p=0.054, Severe Respiratory Insufficiency questionnaire) in favour of NIV. Number of exacerbations, lung function, mood state, daily activity levels or dyspnoea was not significantly different. DISCUSSIONS: We could not demonstrate an improvement in time to readmission or death by adding NIV for 1 year in patients with prolonged hypercapnia after an episode of NIV for ARF. There is no reason to believe the NIV was not effective since daytime PaCO2 and night-time PCO2 improved. The trend for improvement in HRQL favouring NIV we believe nevertheless should be explored further. TRIAL REGISTRATION NUMBER: NTR1100.

Serum uric acid levels and cancer mortality risk among males in a large general population-based cohort study.

PURPOSE: Serum uric acid (SUA) has antioxidant capacities and therefore may protect against the development of cancer. Few epidemiological studies have tested this hypothesis, and findings were inconsistent. METHODS: We studied the association between SUA levels and mortality due to any type of cancer, and three common types of cancer among males (lung, colorectal, and prostate cancer) in the general population-based Vlagtwedde-Vlaardingen cohort with 38 years of follow-up and 8 surveys (total number of males = 4,350). Of 1,823 males with data available on SUA, 254 (13.9 %) died due to any cancer (lung n = 75 (4.1 %), colorectal n = 27 (1.5 %), and prostate cancer n = 23 (1.3 %), assessed on 31 December 2008). SUA, cholesterol, and triglyceride were measured in males during the surveys in 1970, 1972, and 1973. We analyzed the association between cancer mortality risk and SUA level both as continuous variable and as tertiles: lowest <5 mg/dl (reference), middle 5-5.8 mg/dl, and highest >5.8 mg/dl, using multivariate Cox regression with adjustment for age, smoking (pack years), and body mass index. RESULTS: Higher levels of SUA were associated with a lower risk of mortality from any cancer [HR (95 % CI) = 0.85 (0.73-0.97)]. SUA levels in the highest tertile (>5.8 mg/dl) were associated with a lower risk of mortality from any cancer [0.68 (0.48-0.97)]. Additional adjustment for serum total cholesterol and triglyceride levels did not change the results. CONCLUSIONS: Our study indicates that elevated SUA levels may protect against cancer mortality.

Pesticides and other occupational exposures are associated with airway obstruction: the LifeLines cohort study.

OBJECTIVES: Occupational exposures are important and possibly modifiable contributors to the global burden of chronic obstructive pulmonary disease (COPD). Exposure to vapours, gases, dusts and fumes (VGDF) has been associated with a two- to threefold higher COPD risk. Less is known about effects of occupational exposure to pesticides and solvents. In the current study, we assessed if VGDF, pesticides and solvents are associated with the level of lung function and the prevalence of airway obstruction in the general population. METHODS: We included 11 851 subjects aged 18-89 years from the LifeLines cohort study. Regression models assessing associations between occupational exposures (no/low/high), level of lung function (prebronchodilator FEV(1), FEV(1)/FVC) and mild and moderate/severe airway obstruction were adjusted for sex, age, height, weight, current/ex-smoking and packyears. Additionally, we stratified by smoking status and gender and tested for interaction. A second general population cohort (n=2364) was used to verify our initial findings. RESULTS: Occupational exposure to VGDF and pesticides was associated with a lower level of FEV(1) and FEV(1)/FVC and with a higher prevalence of mild and moderate/severe airway obstruction in the two general populations investigated. There were no associations with exposure to solvents. CONCLUSIONS: Occupational exposure to both VGDF and pesticides is associated with airway obstruction in the general population.

Species specific responses to stressors hamper Trichoptera recovery.

Worldwide, aquatic biodiversity is severely threatened as a result of anthropogenic pressures such as pollution, habitat destruction and climate change. Widescale legislation resulted in reduced nutrient- and pesticide loads, and restoration measures allowed modest recovery of freshwater biodiversity. However, from 2010 onwards, recovery in the otherwise unrestored aquatic habitats stagnated. The aim of the present study was therefore to reveal long-term trends in aquatic biodiversity in an anthropogenic landscape and to explain the observed patterns. To this end, over 40 years of biomonitoring data of the indicative taxa group Trichoptera (caddisflies), with an exceptionally high spatial and temporal resolution, was employed. Periods of recovery, stagnation, and decline were delineated using linear and non-linear modelling approaches. Subsequently, species were grouped based on abundance patterns over time and this grouping was used to ascertain species-specific responses to anthropogenic stressors using a trait-based approach. Richness and abundance of all Trichoptera jointly, as well as of the five most abundant and the remaining 136 species, significantly increased from 1980 to significant breakpoints from 2010 onwards, after which these metrics, except the abundances of the 5 most abundant, declined significantly. Trend-based species groupings were not significantly explained by biological traits or ecological preferences. However, Trichoptera species increasing in abundance were less sensitive to climate change and poor water quality, or concerned sensitive species which benefited from restoration measures. Species with stable or declining abundances showed higher sensitivity to climate change. The Trichoptera declining in abundance indicated that conditions in non-protected or restored habitats did not improve due to climate change on top of the other anthropogenic pressures. These observations reinforce the need for increased efforts to improve the only moderately restored water- and habitat quality in anthropogenic landscapes to halt further aquatic ecosystem degradation and to turn biodiversity losses again into recoveries.

Food webs in isolation: The food-web structure of a freshwater reservoir with armoured shores in a former coastal bay area.

Many shallow coastal bays have been closed off from the sea to mitigate the risk of flooding, resulting in coastal reservoir lakes with artificial armoured shorelines. Often these enclosed ecosystems show a persistent decline in biodiversity and ecosystem services, which is likely reflected in their food-web structure. We therefore hypothesize that the food webs of coastal reservoir lakes with armoured shorelines (1) consist of relatively few species with a low food-web connectance and short food chains, and (2) are mainly fuelled by autochthonous organic matter produced in the pelagic zone. To investigate these two hypotheses, we used stable-isotope analysis to determine the food-web structure of lake Markermeer (The Netherlands), a large reservoir lake with armoured shorelines in a former coastal bay area. Contrary to expectation, connectance of the food web in lake Markermeer was comparable to other lakes, while food-chain length was in the higher range. However, the trophic links revealed that numerous macroinvertebrates and fish species in this constructed lake exhibited omnivorous feeding behaviour. Furthermore, in line with our second hypothesis, primary consumers heavily relied on pelagically derived organic matter, while benthic primary production exerted only a minor and seasonal influence on higher trophic levels. Stable-isotope values and the C:N ratio of sediment organic matter in the lake also aligned more closely with phytoplankton than with benthic primary producers. Moreover, terrestrial subsidies of organic matter were virtually absent in lake Markermeer. These findings support the notion that isolation of the lake through shore armouring and the lack of littoral habitats in combination with persistent resuspension of sediments have affected the food web. We argue that restoration initiatives should prioritize the establishment of land-water transition zones, thereby enhancing habitat diversity, benthic primary production, and the inflow of external organic matter while preserving pelagic primary production.