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1.	van Haarlem, M. P., et al. (author) LOFAR : The LOw-Frequency ARray 2013 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 556, s. 1-53 Journal article (peer-reviewed)abstract LOFAR, the LOw-Frequency ARray, is a new-generation radio interferometer constructed in the north of the Netherlands and across europe. Utilizing a novel phased-array design, LOFAR covers the largely unexplored low-frequency range from 10–240 MHz and provides a number of unique observing capabilities. Spreading out from a core located near the village of Exloo in the northeast of the Netherlands, a total of 40 LOFAR stations are nearing completion. A further five stations have been deployed throughout Germany, and one station has been built in each of France, Sweden, and the UK. Digital beam-forming techniques make the LOFAR system agile and allow for rapid repointing of the telescope as well as the potential for multiple simultaneous observations. With its dense core array and long interferometric baselines, LOFAR achieves unparalleled sensitivity and angular resolution in the low-frequency radio regime. The LOFAR facilities are jointly operated by the International LOFAR Telescope (ILT) foundation, as an observatory open to the global astronomical community. LOFAR is one of the first radio observatories to feature automated processing pipelines to deliver fully calibrated science products to its user community. LOFAR’s new capabilities, techniques and modus operandi make it an important pathfinder for the Square Kilometre Array (SKA). We give an overview of the LOFAR instrument, its major hardware and software components, and the core science objectives that have driven its design. In addition, we present a selection of new results from the commissioning phase of this new radio observatory.
2.	Klionsky, Daniel J, et al. (author) Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). 2016 In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 12:1, s. 1-222 Journal article (peer-reviewed)
3.	Aamodt, K., et al. (author) The ALICE experiment at the CERN LHC 2008 In: Journal of Instrumentation. - 1748-0221. ; 3:S08002 Research review (peer-reviewed)abstract ALICE (A Large Ion Collider Experiment) is a general-purpose, heavy-ion detector at the CERN LHC which focuses on QCD, the strong-interaction sector of the Standard Model. It is designed to address the physics of strongly interacting matter and the quark-gluon plasma at extreme values of energy density and temperature in nucleus-nucleus collisions. Besides running with Pb ions, the physics programme includes collisions with lighter ions, lower energy running and dedicated proton-nucleus runs. ALICE will also take data with proton beams at the top LHC energy to collect reference data for the heavy-ion programme and to address several QCD topics for which ALICE is complementary to the other LHC detectors. The ALICE detector has been built by a collaboration including currently over 1000 physicists and engineers from 105 Institutes in 30 countries, Its overall dimensions are 16 x 16 x 26 m(3) with a total weight of approximately 10 000 t. The experiment consists of 18 different detector systems each with its own specific technology choice and design constraints, driven both by the physics requirements and the experimental conditions expected at LHC. The most stringent design constraint is to cope with the extreme particle multiplicity anticipated in central Pb-Pb collisions. The different subsystems were optimized to provide high-momentum resolution as well as excellent Particle Identification (PID) over a broad range in momentum, up to the highest multiplicities predicted for LHC. This will allow for comprehensive studies of hadrons, electrons, muons, and photons produced in the collision of heavy nuclei. Most detector systems are scheduled to be installed and ready for data taking by mid-2008 when the LHC is scheduled to start operation, with the exception of parts of the Photon Spectrometer (PHOS), Transition Radiation Detector (TRD) and Electro Magnetic Calorimeter (EMCal). These detectors will be completed for the high-luminosity ion run expected in 2010. This paper describes in detail the detector components as installed for the first data taking in the summer of 2008.
4.	van Cappellen, W., et al. (author) Apertif: Phased array feeds for the Westerbork Synthesis Radio Telescope: System overview and performance characteristics 2022 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658 Journal article (peer-reviewed)abstract We describe the APERture Tile In Focus (Apertif) system, a phased array feed (PAF) upgrade of the Westerbork Synthesis Radio Telescope that transforms this telescope into a high-sensitivity, wide-field-of-view L-band imaging and transient survey instrument. Using novel PAF technology, up to 40 partially overlapping beams are formed on the sky simultaneously, significantly increasing the survey speed of the telescope. With this upgraded instrument, an imaging survey covering an area of 2300 deg2 is being performed that will deliver both continuum and spectral line datasets, of which the first data have been publicly released. In addition, a time domain transient and pulsar survey covering 15 000 deg2 is in progress. An overview of the Apertif science drivers, hardware, and software of the upgraded telescope is presented, along with its key performance characteristics.
5.	Aamodt, K., et al. (author) Alignment of the ALICE Inner Tracking System with cosmic-ray tracks 2010 In: Journal of Instrumentation. - 1748-0221. ; 5 Conference paper (peer-reviewed)abstract ALICE (A Large Ion Collider Experiment) is the LHC (Large Hadron Collider) experiment devoted to investigating the strongly interacting matter created in nucleus-nucleus collisions at the LHC energies. The ALICE ITS, Inner Tracking System, consists of six cylindrical layers of silicon detectors with three different technologies; in the outward direction: two layers of pixel detectors, two layers each of drift, and strip detectors. The number of parameters to be determined in the spatial alignment of the 2198 sensor modules of the ITS is about 13,000. The target alignment precision is well below 10 mu m in some cases (pixels). The sources of alignment information include survey measurements, and the reconstructed tracks from cosmic rays and from proton-proton collisions. The main track-based alignment method uses the Millepede global approach. An iterative local method was developed and used as well. We present the results obtained for the ITS alignment using about 10(5) charged tracks from cosmic rays that have been collected during summer 2008, with the ALICE solenoidal magnet switched off.
6.	Aamodt, K., et al. (author) First proton-proton collisions at the LHC as observed with the ALICE detector: measurement of the charged-particle pseudorapidity density at root s=900 GeV 2010 In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 65:1-2, s. 111-125 Journal article (peer-reviewed)abstract On 23rd November 2009, during the early commissioning of the CERN Large Hadron Collider (LHC), two counter-rotating proton bunches were circulated for the first time concurrently in the machine, at the LHC injection energy of 450 GeV per beam. Although the proton intensity was very low, with only one pilot bunch per beam, and no systematic attempt was made to optimize the collision optics, all LHC experiments reported a number of collision candidates. In the ALICE experiment, the collision region was centred very well in both the longitudinal and transverse directions and 284 events were recorded in coincidence with the two passing proton bunches. The events were immediately reconstructed and analyzed both online and offline. We have used these events to measure the pseudorapidity density of charged primary particles in the central region. In the range vertical bar eta vertical bar < 0.5, we obtain dN(ch)/d eta = 3.10 +/- 0.13(stat.) +/- 0.22(syst.) for all inelastic interactions, and dN(ch)/d eta = 3.51 +/- 0.15(stat.) +/- 0.25(syst.) for nonsingle diffractive interactions. These results are consistent with previous measurements in proton-antiproton interactions at the same centre-of-mass energy at the CERN Sp<(p)over bar>S collider. They also illustrate the excellent functioning and rapid progress of the LHC accelerator, and of both the hardware and software of the ALICE experiment, in this early start-up phase.
7.	Adams, E. A. K., et al. (author) First release of Apertif imaging survey data 2022 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 667 Journal article (peer-reviewed)abstract Context. Apertif is a phased-array feed system for the Westerbork Synthesis Radio Telescope, providing forty instantaneous beams over 300 MHz of bandwidth. A dedicated survey program utilizing this upgrade started on 1 July 2019, with the last observations taken on 28 February 2022. The imaging survey component provides radio continuum, polarization, and spectral line data. Aims. Public release of data is critical for maximizing the legacy of a survey. Toward that end, we describe the release of data products from the first year of survey operations, through 30 June 2020. In particular, we focus on defining quality control metrics for the processed data products. Methods. The Apertif imaging pipeline, Apercal, automatically produces non-primary beam corrected continuum images, polarization images and cubes, and uncleaned spectral line and dirty beam cubes for each beam of an Apertif imaging observation. For this release, processed data products are considered on a beam-by-beam basis within an observation. We validate the continuum images by using metrics that identify deviations from Gaussian noise in the residual images. If the continuum image passes validation, we release all processed data products for a given beam. We apply further validation to the polarization and line data products and provide flags indicating the quality of those data products. Results. We release all raw observational data from the first year of survey observations, for a total of 221 observations of 160 independent target fields, covering approximately one thousand square degrees of sky. Images and cubes are released on a per beam basis, and 3374 beams (of 7640 considered) are released. The median noise in the continuum images is 41.4 uJy beam(-1), with a slightly lower median noise of 36.9 uJy beam(-1) in the Stokes V polarization image. The median angular resolution is 11.6 ''/sin delta. The median noise for all line cubes, with a spectral resolution of 36.6 kHz, is 1.6 mJy beam(-1), corresponding to a 3-sigma H i column density sensitivity of 1.8 x 10(20) atoms cm(-2) over 20 km s(-1) (for a median angular resolution of 24 '' x 15 ''). Line cubes at lower frequency have slightly higher noise values, consistent with the global RFI environment and overall Apertif system performance. We also provide primary beam images for each individual Apertif compound beam. The data are made accessible using a Virtual Observatory interface and can be queried using a variety of standard tools.
8.	Oostrum, L. C., et al. (author) Repeating fast radio bursts with WSRT/Apertif 2020 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 635 Journal article (peer-reviewed)abstract Context. Repeating fast radio bursts (FRBs) present excellent opportunities to identify FRB progenitors and host environments as well as to decipher the underlying emission mechanism. Detailed studies of repeating FRBs might also hold clues as to the origin of FRBs as a population. Aims. We aim to detect bursts from the first two repeating FRBs, FRB 121102 (R1) and FRB 180814.J0422+73 (R2), and to characterise their repeat statistics. We also want to significantly improve the sky localisation of R2 and identify its host galaxy. Methods. We used the Westerbork Synthesis Radio Telescope to conduct extensive follow-up of these two repeating FRBs. The new phased-array feed system, Apertif, allows one to cover the entire sky position uncertainty of R2 with fine spatial resolution in a single pointing. The data were searched for bursts around the known dispersion measures of the two sources. We characterise the energy distribution and the clustering of detected R1 bursts. Results. We detected 30 bursts from R1. The non-Poissonian nature is clearly evident from the burst arrival times, which is consistent with earlier claims. Our measurements indicate a dispersion measure (DM) of 563.5(2) pc cm(-3), suggesting a significant increase in DM over the past few years. Assuming a constant position angle across the burst, we place an upper limit of 8% on the linear polarisation fraction for the brightest burst in our sample. We did not detect any bursts from R2. Conclusions. A single power-law might not fit the R1 burst energy distribution across the full energy range or widely separated detections. Our observations provide improved constraints on the clustering of R1 bursts. Our stringent upper limits on the linear polarisation fraction imply a significant depolarisation, either intrinsic to the emission mechanism or caused by the intervening medium at 1400 MHz, which is not observed at higher frequencies. The non-detection of any bursts from R2, despite nearly 300 h of observations, implies either a highly clustered nature of the bursts, a steep spectral index, or a combination of the two assuming that the source is still active. Another possibility is that R2 has turned off completely, either permanently or for an extended period of time.
9.	Denes, H., et al. (author) Characterising the Apertif primary beam response 2022 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 667 Journal article (peer-reviewed)abstract Context. Phased array feeds (PAFs) are multi-element receivers in the focal plane of a telescope that make it possible to simultaneously form multiple beams on the sky by combining the complex gains of the individual antenna elements. Recently, the Westerbork Synthesis Radio Telescope (WSRT) was upgraded with PAF receivers to carry out several observing programs, including two imaging surveys and a time-domain survey. The Apertif imaging surveys use a configuration of 40 partially overlapping compound beams (CBs) simultaneously formed on the sky and arranged in an approximately rectangular shape. Aims. This work is aimed at characterising the response of the 40 Apertif CBs to create frequency-resolved I, XX, and YY polarization empirical beam shapes. The measured CB maps can be used for the image deconvolution, primary beam correction, and mosaicking processes of Apertif imaging data. Methods. We used drift scan measurements to measure the response of each of the 40 Apertif CBs. We derived beam maps for all individual beams in I, XX, and YY polarisation in 10 or 18 frequency bins over the same bandwidth as the Apertif imaging surveys. We sampled the main lobe of the beams and the side lobes up to a radius of 0.6 degrees from the beam centres. In addition, we derived beam maps for each individual WSRT dish. Results. We present the frequency and time dependence of the beam shapes and sizes. We compared the compound beam shapes derived with the drift scan method to beam shapes derived with an independent method using a Gaussian Process Regression comparison between the Apertif continuum images and the NRAO VLA Sky Survey (NVSS) catalogue. We find a good agreement between the beam shapes derived with the two independent methods.
10.	Abdulcadir, J, et al. (author) Medically Unnecessary Genital Cutting and the Rights of the Child: Moving Toward Consensus 2019 In: The American journal of bioethics : AJOB. - : Informa UK Limited. - 1536-0075 .- 1526-5161. ; 19:10, s. 17-28 Journal article (other academic/artistic)
11.	Andersen, M. R., et al. (author) Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88 2011 In: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 21:6, s. 885-897 Journal article (peer-reviewed)abstract The filamentous fungus Aspergillus niger exhibits great diversity in its phenotype. It is found globally, both as marine and terrestrial strains, produces both organic acids and hydrolytic enzymes in high amounts, and some isolates exhibit pathogenicity. Although the genome of an industrial enzyme-producing A. niger strain (CBS 513.88) has already been sequenced, the versatility and diversity of this species compel additional exploration. We therefore undertook wholegenome sequencing of the acidogenic A. niger wild-type strain (ATCC 1015) and produced a genome sequence of very high quality. Only 15 gaps are present in the sequence, and half the telomeric regions have been elucidated. Moreover, sequence information from ATCC 1015 was used to improve the genome sequence of CBS 513.88. Chromosome-level comparisons uncovered several genome rearrangements, deletions, a clear case of strain-specific horizontal gene transfer, and identification of 0.8 Mb of novel sequence. Single nucleotide polymorphisms per kilobase (SNPs/kb) between the two strains were found to be exceptionally high (average: 7.8, maximum: 160 SNPs/kb). High variation within the species was confirmed with exo-metabolite profiling and phylogenetics. Detailed lists of alleles were generated, and genotypic differences were observed to accumulate in metabolic pathways essential to acid production and protein synthesis. A transcriptome analysis supported up-regulation of genes associated with biosynthesis of amino acids that are abundant in glucoamylase A, tRNA-synthases, and protein transporters in the protein producing CBS 513.88 strain. Our results and data sets from this integrative systems biology analysis resulted in a snapshot of fungal evolution and will support further optimization of cell factories based on filamentous fungi
12.	Boersma, O. M., et al. (author) A search for radio emission from double-neutron star merger GW190425 using Apertif 2021 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 650 Journal article (peer-reviewed)abstract Context Detection of the electromagnetic emission from coalescing binary neutron stars (BNS) is important for understanding the merger and afterglow. Aims. We present a search for a radio counterpart to the gravitational-wave (GW) source GW190425, a BNS merger, using Apertif on the Westerbork Synthesis Radio Telescope (WSRT). Methods We observed a field of high probability in the associated localisation region for three epochs at ΔTâ€., =â€., 68, 90, 109 d post merger. We identified all sources that exhibit flux variations consistent with the expected afterglow emission of GW190425. We also looked for possible transients. These are sources that are only present in one epoch. In addition, we quantified our ability to search for radio afterglows in the fourth and future observing runs of the GW detector network using Monte Carlo simulations. Results We found 25 afterglow candidates based on their variability. None of these could be associated with a possible host galaxy at the luminosity distance of GW190425. We also found 55 transient afterglow candidates that were only detected in one epoch. All of these candidates turned out to be image artefacts. In the fourth observing run, we predict that up to three afterglows will be detectable by Apertif. Conclusions While we did not find a source related to the afterglow emission of GW190425, the search validates our methods for future searches of radio afterglows.
13.	Altenburger, R., et al. (author) Future water quality monitoring - Adapting tools to deal with mixtures of pollutants in water resource management 2015 In: Science of the Total Environment. - : Elsevier BV. - 0048-9697. ; 512, s. 540-551 Journal article (peer-reviewed)abstract Environmental quality monitoring of water resources is challenged with providing the basis for safeguarding the environment against adverse biological effects of anthropogenic chemical contamination from diffuse and point sources. While current regulatory efforts focus on monitoring and assessing a few legacy chemicals, many more anthropogenic chemicals can be detected simultaneously in our aquatic resources. However, exposure to chemical mixtures does not necessarily translate into adverse biological effects nor clearly shows whether mitigation measures are needed. Thus, the question which mixtures are present and which have associated combined effects becomes central for defining adequate monitoring and assessment strategies. Here we describe the vision of the international, EU-funded project SOLUTIONS, where three routes are explored to link the occurrence of chemical mixtures at specific sites to the assessment of adverse biological combination effects. First of all, multi-residue target and non-target screening techniques covering a broader range of anticipated chemicals co-occurring in the environment are being developed. By improving sensitivity and detection limits for known bioactive compounds of concern, new analytical chemistry data for multiple components can be obtained and used to characterise priority mixtures. This information on chemical occurrence will be used to predict mixture toxicity and to derive combined effect estimates suitable for advancing environmental quality standards. Secondly, bioanalytical tools will be explored to provide aggregate bioactivity measures integrating all components that produce common (adverse) outcomes even for mixtures of varying compositions. The ambition is to provide comprehensive arrays of effect-based tools and trait-based field observations that link multiple chemical exposures to various environmental protection goals more directly and to provide improved in situ observations for impact assessment of mixtures. Thirdly, effect-directed analysis (EDA) will be applied to identify major drivers of mixture toxicity. Refinements of EDA include the use of statistical approaches with monitoring information for guidance of experimental EDA studies. These three approaches will be explored using case studies at the Danube and Rhine river basins as well as rivers of the Iberian Peninsula. The synthesis of findings will be organised to provide guidance for future solution-oriented environmental monitoring and explore more systematic ways to assess mixture exposures and combination effects in future water quality monitoring. (C) 2015 Elsevier B.V. All rights reserved.
14.	Kaye, S, et al. (author) Persistence and Subtype Stability of ADHD Among Substance Use Disorder Treatment Seekers 2019 In: Journal of attention disorders. - : SAGE Publications. - 1557-1246 .- 1087-0547. ; 23:12, s. 1438-1453 Journal article (peer-reviewed)abstract Objective: To examine ADHD symptom persistence and subtype stability among substance use disorder (SUD) treatment seekers. Method: In all, 1,276 adult SUD treatment seekers were assessed for childhood and adult ADHD using Conners’ Adult ADHD Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; CAADID). A total of 290 (22.7%) participants met CAADID criteria for childhood ADHD and comprise the current study sample. Results: Childhood ADHD persisted into adulthood in 72.8% ( n = 211) of cases. ADHD persistence was significantly associated with a family history of ADHD, and the presence of conduct disorder and antisocial personality disorder. The combined subtype was the most stable into adulthood (78.6%) and this stability was significantly associated with conduct disorder and past treatment of ADHD. Conclusion: ADHD is highly prevalent and persistent among SUD treatment seekers and is associated with the more severe phenotype that is also less likely to remit. Routine screening and follow-up assessment for ADHD is indicated to enhance treatment management and outcomes.
15.	Konstenius, M, et al. (author) Childhood trauma exposure in substance use disorder patients with and without ADHD 2017 In: Addictive behaviors. - : Elsevier BV. - 1873-6327 .- 0306-4603. ; 65, s. 118-124 Journal article (peer-reviewed)
16.	Kopczak, Anna, et al. (author) Effect of blood pressure-lowering agents on microvascular function in people with small vessel diseases (TREAT-SVDs) : a multicentre, open-label, randomised, crossover trial 2023 In: The Lancet Neurology. - 1474-4422. ; 22:11, s. 991-1004 Journal article (peer-reviewed)abstract Background: Hypertension is the leading risk factor for cerebral small vessel disease. We aimed to determine whether antihypertensive drug classes differentially affect microvascular function in people with small vessel disease. Methods: We did a multicentre, open-label, randomised crossover trial with blinded endpoint assessment at five specialist centres in Europe. We included participants aged 18 years or older with symptomatic sporadic small vessel disease or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and an indication for antihypertensive treatment. Participants were randomly assigned (1:1:1) to one of three sequences of antihypertensive treatment using a computer-generated multiblock randomisation, stratified by study site and patient group. A 2-week washout period was followed by three 4-week periods of oral monotherapy with amlodipine, losartan, or atenolol at approved doses. The primary endpoint was change in cerebrovascular reactivity (CVR) determined by blood oxygen level-dependent MRI response to hypercapnic challenge in normal-appearing white matter from the end of washout to the end of each treatment period. Efficacy analyses were done by intention-to-treat principles in all randomly assigned participants who had at least one valid assessment for the primary endpoint, and analyses were done separately for participants with sporadic small vessel disease and CADASIL. This trial is registered at ClinicalTrials.gov, NCT03082014, and EudraCT, 2016-002920-10, and is terminated. Findings: Between Feb 22, 2018, and April 28, 2022, 75 participants with sporadic small vessel disease (mean age 64·9 years [SD 9·9]) and 26 with CADASIL (53·1 years [7·0]) were enrolled and randomly assigned to treatment. 79 participants (62 with sporadic small vessel disease and 17 with CADASIL) entered the primary efficacy analysis. Change in CVR did not differ between study drugs in participants with sporadic small vessel disease (mean change in CVR 1·8 × 10–4%/mm Hg [SE 20·1; 95% CI –37·6 to 41·2] for amlodipine; 16·7 × 10–4%/mm Hg [20·0; –22·3 to 55·8] for losartan; –7·1 × 10–4%/mm Hg [19·6; –45·5 to 31·1] for atenolol; poverall=0·39) but did differ in patients with CADASIL (15·7 × 10–4%/mm Hg [SE 27·5; 95% CI –38·3 to 69·7] for amlodipine; 19·4 × 10–4%/mm Hg [27·9; –35·3 to 74·2] for losartan; –23·9 × 10–4%/mm Hg [27·5; –77·7 to 30·0] for atenolol; poverall=0·019). In patients with CADASIL, pairwise comparisons showed that CVR improved with amlodipine compared with atenolol (–39·6 × 10–4%/mm Hg [95% CI –72·5 to –6·6; p=0·019) and with losartan compared with atenolol (–43·3 × 10–4%/mm Hg [–74·3 to –12·3]; p=0·0061). No deaths occurred. Two serious adverse events were recorded, one while taking amlodipine (diarrhoea with dehydration) and one while taking atenolol (fall with fracture), neither of which was related to study drug intake. Interpretation: 4 weeks of treatment with amlodipine, losartan, or atenolol did not differ in their effects on cerebrovascular reactivity in people with sporadic small vessel disease but did result in differential treatment effects in patients with CADASIL. Whether antihypertensive drug classes differentially affect clinical outcomes in people with small vessel diseases requires further research. Funding: EU Horizon 2020 programme.
17.	Lembrechts, Jonas J., et al. (author) SoilTemp : A global database of near-surface temperature 2020 In: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 26:11, s. 6616-6629 Journal article (peer-reviewed)abstract Current analyses and predictions of spatially explicit patterns and processes in ecology most often rely on climate data interpolated from standardized weather stations. This interpolated climate data represents long-term average thermal conditions at coarse spatial resolutions only. Hence, many climate-forcing factors that operate at fine spatiotemporal resolutions are overlooked. This is particularly important in relation to effects of observation height (e.g. vegetation, snow and soil characteristics) and in habitats varying in their exposure to radiation, moisture and wind (e.g. topography, radiative forcing or cold-air pooling). Since organisms living close to the ground relate more strongly to these microclimatic conditions than to free-air temperatures, microclimatic ground and near-surface data are needed to provide realistic forecasts of the fate of such organisms under anthropogenic climate change, as well as of the functioning of the ecosystems they live in. To fill this critical gap, we highlight a call for temperature time series submissions to SoilTemp, a geospatial database initiative compiling soil and near-surface temperature data from all over the world. Currently, this database contains time series from 7,538 temperature sensors from 51 countries across all key biomes. The database will pave the way toward an improved global understanding of microclimate and bridge the gap between the available climate data and the climate at fine spatiotemporal resolutions relevant to most organisms and ecosystem processes.
18.	Ozgen, H, et al. (author) International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder 2020 In: European addiction research. - : S. Karger AG. - 1421-9891 .- 1022-6877. ; 26:4-5, s. 223-232 Journal article (peer-reviewed)abstract <b><i>Background:</i></b> Childhood attention-deficit/hyperactivity disorder (ADHD) is a risk factor for substance misuse and substance use disorder (SUD) in adolescence and (early) adulthood. ADHD and SUD also frequently co-occur in treatment-seeking adolescents, which complicates diagnosis and treatment and is associated with poor treatment outcomes. Research on the effect of treatment of childhood ADHD on the prevention of adolescent SUD is inconclusive, and studies on the diagnosis and treatment of adolescents with ADHD and SUD are scarce. Thus, the available evidence is generally not sufficient to justify robust treatment recommendations. <b><i>Objective:</i></b> The aim of the study was to obtain a consensus statement based on a combination of scientific data and clinical experience. <b><i>Method:</i></b> A modified Delphi study to reach consensus based upon the combination of scientific data and clinical experience with a multidisciplinary group of 55 experts from 17 countries. The experts were asked to rate a set of statements on the effect of treatment of childhood ADHD on adolescent SUD and on the screening, diagnosis, and treatment of adolescents with comorbid ADHD and SUD. <b><i>Results:</i></b> After 3 iterative rounds of rating and adapting 37 statements, consensus was reached on 36 of these statements representing 6 domains: general (<i>n</i> = 4), risk of developing SUD (<i>n</i> = 3), screening and diagnosis (<i>n</i> = 7), psychosocial treatment (<i>n</i> = 5), pharmacological treatment (<i>n</i> = 11), and complementary treatments (<i>n</i> = 7). Routine screening is recommended for ADHD in adolescent patients in substance abuse treatment and for SUD in adolescent patients with ADHD in mental healthcare settings. Long-acting stimulants are recommended as the first-line treatment of ADHD in adolescents with concurrent ADHD and SUD, and pharmacotherapy should preferably be embedded in psychosocial treatment. The only remaining no-consensus statement concerned the requirement of abstinence before starting pharmacological treatment in adolescents with ADHD and concurrent SUD. In contrast to the majority, some experts required full abstinence before starting any pharmacological treatment, some were against the use of stimulants in the treatment of these patients (independent of abstinence), while some were against the alternative use of bupropion. <b><i>Conclusion:</i></b> This international consensus statement can be used by clinicians and patients together in a shared decision-making process to select the best interventions and to reach optimal outcomes in adolescent patients with concurrent ADHD and SUD.
19.	Ozgen, H, et al. (author) [International Consensus Statement for the Screening, Diagnosis, and Treatment of Adolescents with Concurrent Attention-Deficit/Hyperactivity Disorder and Substance Use Disorder] 2022 In: Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie. - : Hogrefe Publishing Group. - 1422-4917 .- 1664-2880. ; 50:1, s. 54-67 Journal article (peer-reviewed)abstract Zusammenfassung. Hintergrund: Eine Aufmerksamkeitsdefizit-/Hyperaktivitätsstörung (ADHS) im Kindesalter stellt einen Risikofaktor für Substanzmissbrauch und Störungen durch Substanzgebrauch (Substance Use Disorder, SUD) in der Pubertät und dem (frühen) Erwachsenenalter dar. ADHS und SUD treten auch häufig bei therapiesuchenden Jugendlichen auf, was die Diagnosestellung und Therapie erschwert sowie mit schlechten Behandlungsergebnissen verbunden ist. Forschungsergebnisse über die Wirkung der Behandlung von ADHS im Kindesalter auf die Prävention von SUD im Jugendalter sind nicht eindeutig und Studien über die Diagnose und Behandlung von Jugendlichen mit ADHS und SUD sind selten. Daher reicht die verfügbare Evidenz allgemein nicht aus, um starke Behandlungsempfehlungen zu rechtfertigen. Fragestellung: Ziel dieser Arbeit war es, eine Konsenserklärung auf der Grundlage von wissenschaftlichen Daten und klinischen Erfahrungen zu erhalten. Methodik: Es wurde eine modifizierte Delphi-Studie durchgeführt, um basierend auf der Kombination von wissenschaftlichen Daten und klinischer Erfahrung mit einer multidisziplinären Gruppe von 55 Expert_innen aus 17 Ländern einen Konsens zu erzielen. Die Expert_innen wurden gebeten, eine Reihe von Aussagen über die Wirkung der Behandlung von ADHS im Kindesalter auf die SUD bei Jugendlichen sowie über das Screening, die Diagnostik und die Behandlung von Jugendlichen mit komorbidem ADHS und SUD zu bewerten. Ergebnisse: Nach drei iterativen Bewertungsrunden und der Anpassung von 37 Aussagen wurde ein Konsens über 36 dieser Aussagen erzielt, die sechs Bereiche repräsentieren: allgemein ( n = 4), Risiko der Entwicklung einer SUD ( n = 3), Screening und Diagnostik ( n = 7), psychosoziale Behandlung ( n = 5), pharmakologische Behandlung ( n = 11) und komplementäre Behandlungen ( n = 7). Der Einsatz von Routinescreenings auf ADHS wird bei adoleszenten Patient_innen in einer Suchtbehandlung ebenso wie Routinescreenings auf SUD bei jugendlichen Patient_innen mit ADHS in allgemeinpsychiatrischen Therapiesettings empfohlen. Langwirksame Stimulanzien werden als Behandlung der ersten Wahl von ADHS bei Jugendlichen mit gleichzeitiger ADHS und SUD empfohlen. Die Pharmakotherapie sollte vorzugsweise in psychosoziale Behandlung eingebettet werden. Die einzige nichtkonsentierte Aussage betraf die Notwendigkeit von Abstinenz vor Beginn einer pharmakologischen Behandlung bei Jugendlichen mit ADHS und gleichzeitigem SUD. Im Gegensatz zur Mehrheit verlangten einige Expert_innen eine vollständige Abstinenz vor Beginn einer pharmakologischen Behandlung, einige waren gegen die Verwendung von Stimulanzien bei der Behandlung dieser Patient_innen (unabhängig von Abstinenz), während einige sich gegen die alternative Anwendung von Bupropion aussprachen. Schlussfolgerungen: Diese internationale Konsenserklärung kann von Kliniker_innen und Patient_innen zusammen in einem gemeinsamen Entscheidungsprozess genutzt werden, um die besten Interventionen auszuwählen und die bestmöglichen Ergebnisse bei adoleszenten Patient_innen mit gleichzeitiger ADHS und SUD zu erzielen.
20.	Palma-Álvarez, RF, et al. (author) Validity of the ADHD module of the Mini International Neuropsychiatric Interview PLUS for screening of adult ADHD in treatment seeking substance use disorder patients: ADHD screening with MINI-Plus 2023 In: Spanish journal of psychiatry and mental health. - : Elsevier BV. - 2950-2853. ; 16:1, s. 11-15 Journal article (peer-reviewed)
21.	Skutle, A, et al. (author) Early developmental, temperamental and educational problems in 'substance use disorder' patients with and without ADHD. Does ADHD make a difference? 2015 In: Addictive behaviors reports. - : Elsevier BV. - 2352-8532. ; 2, s. 13-18 Journal article (peer-reviewed)
22.	van de Glind, G, et al. (author) Validity of the Adult ADHD Self-Report Scale (ASRS) as a screener for adult ADHD in treatment seeking substance use disorder patients 2013 In: Drug and alcohol dependence. - : Elsevier BV. - 1879-0046 .- 0376-8716. ; 132:3, s. 587-596 Journal article (peer-reviewed)
23.	van de Glind, G, et al. (author) Variability in the prevalence of adult ADHD in treatment seeking substance use disorder patients: results from an international multi-center study exploring DSM-IV and DSM-5 criteria 2014 In: Drug and alcohol dependence. - : Elsevier BV. - 1879-0046 .- 0376-8716. ; 134, s. 158-166 Journal article (peer-reviewed)
24.	van Emmerik-van Oortmerssen, K, et al. (author) Psychiatric comorbidity in treatment-seeking substance use disorder patients with and without attention deficit hyperactivity disorder: results of the IASP study 2014 In: Addiction (Abingdon, England). - : Wiley. - 1360-0443 .- 0965-2140. ; 109:2, s. 262-272 Journal article (peer-reviewed)
25.	Van Eunen, K., et al. (author) Measuring enzyme activities under standardized in-vivo like conditions for systems biology 2010 In: FEBS Journal. - : Wiley. - 1742-4658 .- 1742-464X. ; 277:3, s. 749-760 Journal article (peer-reviewed)abstract Realistic quantitative models require data from many laboratories. Therefore, standardization of experimental systems and assay conditions is crucial. Moreover, standards should be representative of the in vivo conditions. However, most often, enzyme-kinetic parameters are measured under assay conditions that yield the maximum activity of each enzyme. In practice, this means that the kinetic parameters of different enzymes are measured in different buffers, at different pH values, with different ionic strengths, etc. In a joint effort of the Dutch Vertical Genomics Consortium, the European Yeast Systems Biology Network and the Standards for Reporting Enzymology Data Commission, we have developed a single assay medium for determining enzyme-kinetic parameters in yeast. The medium is as close as possible to the in vivo situation for the yeast Saccharomyces cerevisiae, and at the same time is experimentally feasible. The in vivo conditions were estimated for S. cerevisiae strain CEN. PK113-7D grown in aerobic glucose-limited chemostat cultures at an extracellular pH of 5.0 and a specific growth rate of 0.1 h(-1). The cytosolic pH and concentrations of calcium, sodium, potassium, phosphorus, sulfur and magnesium were determined. On the basis of these data and literature data, we propose a defined in vivo-like medium containing 300 mm potassium, 50 mm phosphate, 245 mm glutamate, 20 mm sodium, 2 mm free magnesium and 0.5 mm calcium, at a pH of 6.8. The V(max) values of the glycolytic and fermentative enzymes of S. cerevisiae were measured in the new medium. For some enzymes, the results deviated conspicuously from those of assays done under enzyme-specific, optimal conditions
26.	van Oosten, H. Herman, et al. (author) Hatching failure and accumulation of organic pollutants through the terrestrial food web of a declining songbird in Western Europe 2019 In: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 650:1, s. 1547-1553 Journal article (peer-reviewed)abstract Population growth in passerine birds is largely driven by fecundity. If fecundity is affected, for instance by hatching failure, populations may decline. We noted high hatching failure of up to 27% per year in relict populations of the Northern wheatear (Oenanthe oenanthe) in The Netherlands, a strongly declining, migratory passerine in Europe. This hatching failure itself can cause population decline, irrespective of other adverse factors. Additionally, we investigated the cause of hatching failure. Unhatched eggs showed egg yolk infections or embryonic malformations, part of which is associated with the actions of dioxin-like compounds (DLCs). Indeed, DLCs appear to bioaccumulate in the local foodweb, where the soil contained only background concentrations, similar to those found at many other locations. DLC concentrations in Dutch eggs were six-fold higher than those in a reference population in Sweden, where egg failure was only 6%. However, Northern wheatears appear to be only moderately sensitive to the actions of DLCs, because of their specific Ah-receptor type which may moderate the receptor mediated effects of DLCs. This indicates that the concentrations of DLCs, although elevated, may not have caused the embryo malformations or the low hatching rates. We discuss whether other toxins may be important or imbalances in the nutrition and if inbreeding may play a larger role than expected.
27.	Wapp, M, et al. (author) Risk Factors for Borderline Personality Disorder in Treatment Seeking Patients with a Substance Use Disorder: An International Multicenter Study 2015 In: European addiction research. - : S. Karger AG. - 1421-9891 .- 1022-6877. ; 21:4, s. 188-194 Journal article (peer-reviewed)abstract Borderline personality disorder (BPD) and substance use disorders (SUDs) often co-occur, partly because they share risk factors. In this international multicenter study, risk factors for BPD were examined for SUD patients. In total, 1,205 patients were comprehensively examined by standardized interviews and questionnaires on psychiatric diagnosis and risk factors, and it was found that 1,033 (85.7%) had SUDs without BPD (SUD) and 172 (14.3%) had SUD with BPD (SUD + BPD). SUD + BPD patients were significantly younger, more often females and more often diagnosed with comorbid adult attention deficit/hyperactivity disorder. SUD + BPD patients did not differ from SUD patients on most risk factors typical for SUD such as maternal use of drugs during pregnancy or parents having any SUD. However, SUD + BPD patients did have a higher risk of having experienced emotional and physical abuse, neglect, or family violence in childhood compared to SUD patients, suggesting that child abuse and family violence are BPD-specific risk factors in patients with SUDs.
28.	Awes, T., et al. (author) Design and performance of a silicon–tungsten calorimeter prototype module and the associated readout 2021 In: Nuclear Instruments and Methods in Physics Research, Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. - : Elsevier BV. - 0168-9002. ; 988 Journal article (peer-reviewed)abstract We describe the details of a silicon–tungsten prototype electromagnetic calorimeter module and associated readout electronics. Detector performance for this prototype has been measured in test beam experiments at the CERN PS and SPS accelerator facilities in 2015/16. The results are compared to those in Monte Carlo Geant4 simulations. This is the first real-world demonstration of the performance of a custom ASIC designed for fast, lower-power, high-granularity applications.
29.	Dulio, Valeria, et al. (author) The NORMAN Association and the European Partnership for Chemicals Risk Assessment (PARC) : let’s cooperate! 2020 In: Environmental Sciences Europe. - : Springer. - 2190-4707 .- 2190-4715. ; 32:1 Journal article (peer-reviewed)abstract The Partnership for Chemicals Risk Assessment (PARC) is currently under development as a joint research and innovation programme to strengthen the scientific basis for chemical risk assessment in the EU. The plan is to bring chemical risk assessors and managers together with scientists to accelerate method development and the production of necessary data and knowledge, and to facilitate the transition to next-generation evidence-based risk assessment, a non-toxic environment and the European Green Deal. The NORMAN Network is an independent, well-established and competent network of more than 80 organisations in the field of emerging substances and has enormous potential to contribute to the implementation of the PARC partnership. NORMAN stands ready to provide expert advice to PARC, drawing on its long experience in the development, harmonisation and testing of advanced tools in relation to chemicals of emerging concern and in support of a European Early Warning System to unravel the risks of contaminants of emerging concern (CECs) and close the gap between research and innovation and regulatory processes. In this commentary we highlight the tools developed by NORMAN that we consider most relevant to supporting the PARC initiative: (i) joint data space and cutting-edge research tools for risk assessment of contaminants of emerging concern; (ii) collaborative European framework to improve data quality and comparability; (iii) advanced data analysis tools for a European early warning system and (iv) support to national and European chemical risk assessment thanks to harnessing, combining and sharing evidence and expertise on CECs. By combining the extensive knowledge and experience of the NORMAN network with the financial and policy-related strengths of the PARC initiative, a large step towards the goal of a non-toxic environment can be taken.
30.	Faraone, SV, et al. (author) The World Federation of ADHD International Consensus Statement: 208 Evidence-based conclusions about the disorder 2021 In: Neuroscience and biobehavioral reviews. - : Elsevier BV. - 1873-7528 .- 0149-7634. ; 128, s. 789-818 Journal article (peer-reviewed)
31.	Kopczak, Anna, et al. (author) The EffecTs of Amlodipine and other Blood PREssure Lowering Agents on Microvascular FuncTion in Small Vessel Diseases (TREAT-SVDs) trial : Study protocol for a randomised crossover trial 2023 In: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 8:1, s. 387-397 Journal article (peer-reviewed)abstract Background: Hypertension is the leading modifiable risk factor for cerebral small vessel diseases (SVDs). Yet, it is unknown whether antihypertensive drug classes differentially affect microvascular function in SVDs. Aims: To test whether amlodipine has a beneficial effect on microvascular function when compared to either losartan or atenolol, and whether losartan has a beneficial effect when compared to atenolol in patients with symptomatic SVDs. Design: TREAT-SVDs is an investigator-led, prospective, open-label, randomised crossover trial with blinded endpoint assessment (PROBE design) conducted at five study sites across Europe. Patients aged 18 years or older with symptomatic SVD who have an indication for antihypertensive treatment and are suffering from either sporadic SVD and a history of lacunar stroke or vascular cognitive impairment (group A) or CADASIL (group B) are randomly allocated 1:1:1 to one of three sequences of antihypertensive treatment. Patients stop their regular antihypertensive medication for a 2-week run-in period followed by 4-week periods of monotherapy with amlodipine, losartan and atenolol in random order as open-label medication in standard dose. Outcomes: The primary outcome measure is cerebrovascular reactivity (CVR) as determined by blood oxygen level dependent brain MRI signal response to hypercapnic challenge with change in CVR in normal appearing white matter as primary endpoint. Secondary outcome measures are mean systolic blood pressure (BP) and BP variability (BPv). Discussion: TREAT-SVDs will provide insights into the effects of different antihypertensive drugs on CVR, BP, and BPv in patients with symptomatic sporadic and hereditary SVDs. Funding: European Union’s Horizon 2020 programme. Trial registration: NCT03082014.
32.	Parma, Valentina, et al. (author) More Than Smell—COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis 2020 In: Chemical Senses. - : Oxford University Press (OUP). - 0379-864X .- 1464-3553. ; 45:7, s. 609-622 Journal article (peer-reviewed)abstract Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19–79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (−79.7 ± 28.7, mean ± standard deviation), taste (−69.0 ± 32.6), and chemesthetic (−37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.
33.	Van den Brink, P. J., et al. (author) Toward sustainable environmental quality: Priority research questions for Europe 2018 In: Environmental Toxicology and Chemistry. - : Wiley. - 0730-7268 .- 1552-8618. ; 37:9, s. 2281-2295 Journal article (peer-reviewed)abstract The United Nations' Sustainable Development Goals have been established to end poverty, protect the planet, and ensure prosperity for all. Delivery of the Sustainable Development Goals will require a healthy and productive environment. An understanding of the impacts of chemicals which can negatively impact environmental health is therefore essential to the delivery of the Sustainable Development Goals. However, current research on and regulation of chemicals in the environment tend to take a simplistic view and do not account for the complexity of the real world, which inhibits the way we manage chemicals. There is therefore an urgent need for a step change in the way we study and communicate the impacts and control of chemicals in the natural environment. To do this requires the major research questions to be identified so that resources are focused on questions that really matter. We present the findings of a horizon-scanning exercise to identify research priorities of the European environmental science community around chemicals in the environment. Using the key questions approach, we identified 22 questions of priority. These questions covered overarching questions about which chemicals we should be most concerned about and where, impacts of global megatrends, protection goals, and sustainability of chemicals; the development and parameterization of assessment and management frameworks; and mechanisms to maximize the impact of the research. The research questions identified provide a first-step in the path forward for the research, regulatory, and business communities to better assess and manage chemicals in the natural environment. Environ Toxicol Chem 2018;37:2281-2295. (c) 2018 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC.
34.	Adewumi, Oluseun, et al. (author) Characterization of human embryonic stem cell lines by the International Stem Cell Initiative 2007 In: Nature Biotechnology. - : Springer Science and Business Media LLC. - 1087-0156 .- 1546-1696. ; 25:7, s. 803-816 Journal article (peer-reviewed)abstract The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected.
35.	Androulakakis, Andreas, et al. (author) Determination of 56 per- and polyfluoroalkyl substances in top predators and their prey from Northern Europe by LC-MS/MS 2022 In: Chemosphere. - : Elsevier. - 0045-6535 .- 1879-1298. ; 287, s. 131775-131775 Journal article (peer-reviewed)
36.	Baalousha, M., et al. (author) Modeling nanomaterial fate and uptake in the environment: current knowledge and future trends 2016 In: Environmental Science-Nano. - : Royal Society of Chemistry (RSC). - 2051-8153 .- 2051-8161. ; 3:2, s. 323-345 Journal article (peer-reviewed)abstract Modeling the environmental fate of nanomaterials (NMs) and their uptake by cells and organisms in the environment is essential to underpin experimental research, develop overarching theories, improve our fundamental understanding of NM exposure and hazard, and thus enable risk assessment of NMs. Here, we critically review the state-of-the-art of the available models that can be applied/adapted to quantify/predict NM fate and uptake in aquatic and terrestrial systems and make recommendations regarding future directions for model development. Fate models have evolved from substance flow analysis models that lack nano-specific processes to more advanced mechanistic models that (at least partially) take nano-specific (typically non-equilibrium, dynamic) processes into account, with a focus on key fate processes such as agglomeration, sedimentation and dissolution. Similarly, NM uptake by organisms is driven by dynamic processes rather than by equilibrium partitioning. Hence, biokinetic models are more suited to model NM uptake, compared with the simple bio-accumulation factors used for organic compounds. Additionally, biokinetic models take speciation processes (e.g. particulate versus ionic uptake) into account, although identifying essential environment-specific processes to include in models remains a challenge. The models developed so far require parameterization, calibration and validation with available data, e.g. field data (if available), or experimental data (e.g. aquatic and terrestrial mesocosms), rather than extension to more complex and sophisticated models that include all possible transformation processes. Collaborative efforts between experimentalists and modelers to generate appropriate ground-truth data would advance the field most rapidly.
37.	Crunelle, CL, et al. (author) International Consensus Statement on Screening, Diagnosis and Treatment of Substance Use Disorder Patients with Comorbid Attention Deficit/Hyperactivity Disorder 2018 In: European addiction research. - : S. Karger AG. - 1421-9891 .- 1022-6877. ; 24:1, s. 43-51 Journal article (peer-reviewed)abstract Adult attention deficit/hyperactivity disorder (ADHD) often co-occurs with substance use disorders (SUD) and is associated with early onset and more severe development of SUD and with reduced treatment effectiveness. Screening tools allow for a good recognition of possible ADHD in adults with SUD and should be used routinely, followed by an ADHD diagnostic process initiated as soon as possible. Simultaneous and integrated treatment of ADHD and SUD, using a combination of pharmaco- and psychotherapy, is recommended. Long-acting methylphenidate, extended-release amphetamines, and atomoxetine with up-titration to higher dosages may be considered in patients unresponsive to standard doses. This paper includes evidence- and consensus-based recommendations developed to provide guidance in the screening, diagnosis and treatment of patients with ADHD-SUD comorbidity.
38.	Gómez-Ramírez, P, et al. (author) An overview of existing raptor contaminant monitoring activities in Europe 2014 In: Environment International. - : Elsevier. - 0160-4120. ; 67, s. 12-21 Journal article (peer-reviewed)abstract Biomonitoring using raptors as sentinels can provide early warning of the potential impacts of contaminants on humans and the environment and also a means of tracking the success of associated mitigation measures. Examples include detection of heavy metal-induced immune system impairment, PCB-induced altered reproductive impacts, and toxicity associated with lead in shot game. Authorisation of such releases and implementation of mitigation is now increasingly delivered through EU-wide directives but there is little established pan-European monitoring to quantify outcomes. We investigated the potential for EU-wide coordinated contaminant monitoring using raptors as sentinels. We did this using a questionnaire to ascertain the current scale of national activity across 44 European countries. According to this survey, there have been 52 different contaminant monitoring schemes with raptors over the last 50 years. There were active schemes in 15 (predominantly western European) countries and 23 schemes have been running for >20 years; most monitoring was conducted for >5 years. Legacy persistent organic compounds (specifically organochlorine insecticides and PCBs), and metals/metalloids were monitored in most of the 15 countries. Fungicides, flame retardants and anticoagulant rodenticides were also relatively frequently monitored (each in at least 6 countries). Common buzzard (Buteo buteo), common kestrel (Falco tinnunculus), golden eagle (Aquila chrysaetos), white-tailed sea eagle (Haliaeetus albicilla), peregrine falcon (Falco peregrinus), tawny owl (Strix aluco) and barn owl (Tyto alba) were most commonly monitored (each in 6–10 countries). Feathers and eggs were most widely analysed although many schemes also analysed body tissues. Our study reveals an existing capability across multiple European countries for contaminant monitoring using raptors. However, coordination between existing schemes and expansion of monitoring into Eastern Europe is needed. This would enable assessment of the appropriateness of the EU-regulation of substances that are hazardous to humans and the environment, the effectiveness of EU level mitigation policies, and identify pan-European spatial and temporal trends in current and emerging contaminants of concern.
39.	Gonzalez, RA, et al. (author) Onset and Severity of Early Disruptive Behavioral Disorders in Treatment-Seeking Substance Use Disorder Patients with and without Attention-Deficit/Hyperactivity Disorder 2020 In: European addiction research. - : S. Karger AG. - 1421-9891 .- 1022-6877. ; 26:4-5, s. 211-222 Journal article (peer-reviewed)abstract <b><i>Aims:</i></b> This study addressed the age of onset of conduct disorder (CD) and oppositional defiant disorder (ODD) in treatment-seeking substance use disorder (SUD) patients with and without adult attention-deficit/hyperactivity disorder (ADHD) and its association with early onset of SUD. <b><i>Methods:</i></b> We examined data from the 2nd <i>International ADHD in Substance Use Disorders Prevalence Study</i>, including 400 adults in SUD treatment from Puerto Rico, Hungary, and Australia. ADHD, SUD, and CD/ODD were assessed with the <i>Conners Adult ADHD Diagnostic Interview for DSM-IV</i>, the <i>MINI International Neuropsychiatric Interview</i>, and the K-SADS, respectively. Cox regression analyses modeled time to emergence of CD/ODD separately for SUD patients with and without adult ADHD. Linear regression models examined associations between age of onset of SUD and presence of ADHD and adjusted for sex, age, and country. To assess the mediating role of CD/ODD on the association of ADHD with onset of SUD, adjusted regression models were estimated. <b><i>Results:</i></b> Treatment-seeking SUD patients with ADHD presented an earlier onset of CD/ODD compared with those without ADHD. CD/ODD symptom loads were higher among the SUD and ADHD group. Age of first substance use and SUD were significantly earlier in SUD patients with ADHD, and these findings remained significant after adjustment for demographics and coexisting CD/ODD. <b><i>Conclusions:</i></b> ADHD is associated with earlier onset of SUD as well as with an earlier onset of more frequent and more severe disruptive behavioral disorders. These findings may inform preventive interventions to mitigate adverse consequences of ADHD.
40.	Guiraud, J., et al. (author) Sodium Oxybate for Alcohol Dependence: A Network Meta-Regression Analysis Considering Population Severity at Baseline and Treatment Duration 2023 In: Alcohol and Alcoholism. - : Oxford University Press (OUP). - 0735-0414 .- 1464-3502. ; 58:2, s. 125-133 Journal article (peer-reviewed)abstract Aims: The estimated effect of sodium oxybate (SMO) in the treatment of alcohol dependence is heterogeneous. Population severity and treatment duration have been identified as potential effect modifiers. Population severity distinguishes heavy drinking patients with <14 days of abstinence before treatment initiation (high-severity population) from other patients (mild-severity population). Treatment duration reflects the planned treatment duration. This study aimed to systematically investigate the effect of these potential effect moderators on SMO efficacy in alcohol-dependent patients. Methods: Network meta-regression allows for testing potential effect modifiers. It was selected to investigate the effect of the above factors on SMO efficacy defined as continuous abstinence (abstinence rate) and the percentage of days abstinent (PDA). Randomized controlled trials for alcohol dependence with at least one SMO group conducted in high-severity and mild-severity populations were assigned to a high-severity and mild-severity group of studies, respectively. Results: Eight studies (1082 patients) were retained: four in the high-severity group and four in the mild-severity group. The high-severity group was associated with larger SMO effect sizes than the mild-severity group: abstinence rate risk ratio (RR) 3.16, P = 0.004; PDA +26.9%, P < 0.001. For PDA, longer treatment duration was associated with larger SMO effect size: +11.3% per extra month, P < 0.001. In the high-severity group, SMO showed benefit: abstinence rate RR 2.91, P = 0.03; PDA +16.9%, P < 0.001. In the mild-severity group, SMO showed benefit only in PDA for longer treatment duration: +23.9%, P < 0.001. Conclusions: In the retained studies with alcohol-dependent patients, high-severity population and longer treatment duration were associated with larger SMO effect sizes.
41.	Guiraud, J., et al. (author) Sodium oxybate for the maintenance of abstinence in alcohol-dependent patients: An international, multicenter, randomized, double-blind, placebo-controlled trial 2022 In: Journal of Psychopharmacology. - : SAGE Publications. - 0269-8811 .- 1461-7285. ; 36:10 Journal article (peer-reviewed)abstract Background: Sodium oxybate (SMO) has been shown to be effective in the maintenance of abstinence (MoA) in alcohol-dependent patients in a series of small randomized controlled trials (RCTs). These results needed to be confirmed by a large trial investigating the treatment effect and its sustainability after medication discontinuation. Aims: To confirm the SMO effect on (sustained) MoA in detoxified alcohol-dependent patients. Methods: Large double-blind, randomized, placebo-controlled trial in detoxified adult alcohol-dependent outpatients (80% men) from 11 sites in four European countries. Patients were randomized to 6 months SMO (3.3-3.9 g/day) or placebo followed by a 6-month medication-free period. Primary outcome was the cumulative abstinence duration (CAD) during the 6-month treatment period defined as the number of days with no alcohol use. Secondary outcomes included CAD during the 12-month study period. Results: Of the 314 alcohol-dependent patients randomized, 154 received SMO and 160 received placebo. Based on the pre-specified fixed-effect two-way analysis of variance including the treatment-by-site interaction, SMO showed efficacy in CAD during the 6-month treatment period: mean difference +43.1 days, 95% confidence interval (17.6-68.5; p = 0.001). Since significant heterogeneity of effect across sites and unequal sample sizes among sites (n = 3-66) were identified, a site-level random meta-analysis was performed with results supporting the pre-specified analysis: mean difference +32.4 days, p = 0.014. The SMO effect was sustained during the medication-free follow-up period. SMO was well-tolerated. Conclusions: Results of this large RCT in alcohol-dependent patients demonstrated a significant and clinically relevant sustained effect of SMO on CAD.
42.	Kapitány-Fövény, M, et al. (author) [Recommendations for the screening, diagnosis and treatment of patients with comorbid attention deficit hyperactivity- and substance use disorder] 2020 In: Psychiatria Hungarica : A Magyar Pszichiatriai Tarsasag tudomanyos folyoirata. - 0237-7896. ; 35:4, s. 435-447 Journal article (peer-reviewed)
43.	Scherrer, B., et al. (author) Baseline severity and the prediction of placebo response in clinical trials for alcohol dependence: A meta-regression analysis to develop an enrichment strategy 2021 In: Alcoholism-Clinical and Experimental Research. - : Wiley. - 0145-6008 .- 1530-0277. ; 45:9, s. 1722-1734 Journal article (peer-reviewed)abstract Background There is considerable unexplained variability in alcohol abstinence rates (AR) in the placebo groups of randomized controlled trials (RCTs) for alcohol dependence (AD). This is of particular interest because placebo responses correlate negatively with treatment effect size. Recent evidence suggests that the placebo response is lower in very heavy drinkers who show no "spontaneous improvement" prior to treatment initiation (high-severity population) than in a mild-severity population and in studies with longer treatment duration. We systematically investigated the relationship between population severity, treatment duration, and the placebo response in AR to inform a strategy aimed at reducing the placebo response and thereby increasing assay sensitivity in RCTs for AD. Methods We conducted a systematic literature review on placebo-controlled RCTs for AD.We assigned retained RCTs to high- or mild-severity groups of studies based on baseline drinking risk levels and abstinence duration before treatment initiation. We tested the effects of population severity and treatment duration on the placebo response in AR using meta-regression analysis. Results Among the 19 retained RCTs (comprising 1996 placebo-treated patients), 11 trials were high-severity and 8 were mild-severity RCTs. The between-study variability in AR was lower in the high-severity than in the mild-severity studies (interquartile range: 7.4% vs. 20.9%). The AR in placebo groups was dependent on population severity (p = 0.004) and treatment duration (p = 0.017) and was lower in the high-severity studies (16.8% at 3 months) than the mild-severity studies (36.7% at 3 months). Conclusions Pharmacological RCTs for AD should select high-severity patients to decrease the magnitude and variability in the placebo effect and and improve the efficiency of drug development efforts for AD.
44.	Schroeder, J., et al. (author) Fewer invited talks by women in evolutionary biology symposia 2013 In: Journal of evolutionary biology. - : Wiley. - 1420-9101 .- 1010-061X. ; 26:9, s. 2063-2069 Journal article (peer-reviewed)abstract Lower visibility of female scientists, compared to male scientists, is a potential reason for the under-representation of women among senior academic ranks. Visibility in the scientific community stems partly from presenting research as an invited speaker at organized meetings. We analysed the sex ratio of presenters at the European Society for Evolutionary Biology (ESEB) Congress 2011, where all abstract submissions were accepted for presentation. Women were under-represented among invited speakers at symposia (15% women) compared to all presenters (46%), regular oral presenters (41%) and plenary speakers (25%). At the ESEB congresses in 2001-2011, 9-23% of invited speakers were women. This under-representation of women is partly attributable to a larger proportion of women, than men, declining invitations: in 2011, 50% of women declined an invitation to speak compared to 26% of men. We expect invited speakers to be scientists from top ranked institutions or authors of recent papers in high-impact journals. Considering all invited speakers (including declined invitations), 23% were women. This was lower than the baseline sex ratios of early-mid career stage scientists, but was similar to senior scientists and authors that have published in high-impact journals. High-quality science by women therefore has low exposure at international meetings, which will constrain Evolutionary Biology from reaching its full potential. We wish to highlight the wider implications of turning down invitations to speak, and encourage conference organizers to implement steps to increase acceptance rates of invited talks.
45.	Van de Glind, G, et al. (author) The International Collaboration on ADHD and Substance Abuse (ICASA): Mission, Results, and Future Activities 2020 In: European addiction research. - : S. Karger AG. - 1421-9891 .- 1022-6877. ; 26:4-5, s. 173-178 Journal article (peer-reviewed)abstract <b><i>Background:</i></b> The <i>International Collaboration on ADHD and Substance Abuse</i> (ICASA) is a network of 28 centers from 16 countries initiated to investigate the link between attention deficit-hyperactivity disorder (ADHD) and substance use disorder (SUD). In this article, we present the mission, the results of finished studies, and the current and future research projects of ICASA. Methods: During the past 10 years, 3 cross-sectional studies were conducted: two International ADHD in Substance use disorders Prevalence (IASP-1 and IASP-2) studies, directed at the screening, diagnosis, and the prevalence of adult ADHD in treatment-seeking patients with SUD, and the Continuous performance test for ADHD in SUD Patients (CASP) study, testing a novel continuous performance test in SUD patients with and without adult ADHD. Recently, the prospective International Naturalistic Cohort Study of ADHD and Substance Use Disorders (INCAS) was initiated, directed at treatment provision and treatment outcome in SUD patients with adult ADHD. <b><i>Results:</i></b> The IASP studies have shown that approximately 1 in 6 adult treatment-seeking SUD patients also have ADHD. In addition, those SUD patients with adult ADHD compared to SUD patients without ADHD report more childhood trauma exposure, slower infant development, greater problems controlling their temperament, and lower educational attainment. Comorbid patients also reported more risk-taking behavior, and a higher rate of other psychiatric disorders compared to SUD patients without ADHD. Screening, diagnosis, and treatment of this patient group are possible even before abstinence has been achieved. The results of the CASP study are reported separately in this special issue. <b><i>Conclusions:</i></b> The ICASA research to date has demonstrated a high prevalence of comorbid ADHD and SUD, associated with elevated rates of additional comorbidities and risk factors for adverse outcomes. More research is needed to find the best way to treat these patients, which is the main topic of the ongoing INCAS study.
46.	van den Brink, W., et al. (author) Efficacy and safety of sodium oxybate in alcohol-dependent patients with a very high drinking risk level 2018 In: Addiction Biology. - : Wiley. - 1355-6215 .- 1369-1600. ; 23:4, s. 969-986 Journal article (peer-reviewed)abstract Medication development for alcohol relapse prevention or reduction of consumption is highly challenging due to methodological issues of pharmacotherapy trials. Existing approved medications are only modestly effective with many patients failing to benefit from these therapies. Therefore, there is a pressing need for other effective treatments with a different mechanism of action, especially for patients with very high (VH) drinking risk levels (DRL) because this is the most severely affected population of alcohol use disorder patients. Life expectancy of alcohol-dependent patients with a VH DRL is reduced by 22 years compared with the general population and approximately 90000 alcohol-dependent subjects with a VH DRL die prematurely each year in the EU (Rehm et al. 2018). A promising new medication for this population is sodium oxybate, a compound that acts on GABA(B) receptors and extrasynaptic GABA(A) receptors resulting in alcohol-mimetic effects. In this article, a European expert group of alcohol researchers and clinicians summarizes data (a) from published trials, (b) from two new-as yet unpublished-large clinical trials (GATE 2 (n = 314) and SMO032 (n = 496), (c) from post hoc subgroup analyses of patients with different WHO-defined DRLs and (d) from multiple meta-analyses. These data provide convergent evidence that sodium oxybate is effective especially in a subgroup of alcohol-dependent patients with VH DRLs. Depending on the study, abstinence rates are increased up to 34 percent compared with placebo with risk ratios up to 6.8 in favor of sodium oxybate treatment. These convergent data are supported by the clinical use of sodium oxybate in Austria and Italy for more than 25years. Sodium oxybate is the sodium salt of gamma-hydroxybutyric acid that is also used as a recreational (street) drug suggestive of abuse potential. However, a pharmacovigilance database of more than 260000 alcohol-dependent patients treated with sodium oxybate reported very few adverse side effects and only few cases of abuse. We therefore conclude that sodium oxybate is an effective, well-tolerated and safe treatment for withdrawal and relapse prevention treatment, especially in alcohol-dependent patients with VH DRL.
47.	Backhaus, Thomas, 1967, et al. (author) Assessing the ecological impact of chemical pollution on aquatic ecosystems requires the systematic exploration and evaluation of four lines of evidence 2019 In: Environmental Sciences Europe. - : Springer Science and Business Media LLC. - 2190-4707 .- 2190-4715. ; 31:1 Journal article (peer-reviewed)abstract The aim of the European Water Framework Directive is to ensure good ecological status for all European surface waters. However, although current monitoring strategies aim to identify the presence and magnitude of ecological impacts, they provide little information on the causes of an ecosystem impairment. In fact, approaches to establish causal links between chemical pollution and impacts on the ecological status of exposed aquatic systems are largely lacking or poorly described and established. This is, however, crucial for developing and implementing appropriately targeted water management strategies. In order to identify the role of chemical pollution on the ecological status of an aquatic ecosystem, we suggest to systematically combine four lines of evidence (LOEs) that provide complementary evidence on the presence and potential ecological impact of complex chemical pollution: (1) component-based methods that allow a predictive mixture risk modeling; (2) effect-based methods; (3) in situ tests; (4) field-derived species inventories. These LOEs differ systematically in their specificity for chemical pollution, data demands, resources required and ecological relevance. They complement each other and, in their combination, allow to assess the contribution of chemical pollution pressure to impacts on ecological structure and function. Data from all LOEs are not always available and the information they provide is not necessarily consistent. We therefore propose a systematic, robust and transparent approach to combine the information available for a given study, in order to ensure that consensual conclusions are drawn from a given dataset. This allows to identify critical data gaps and needs for future testing and/or options for targeted and efficient water management.
48.	Bouget, D., et al. (author) Preoperative Brain Tumor Imaging: Models and Software for Segmentation and Standardized Reporting 2022 In: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 13 Journal article (peer-reviewed)abstract For patients suffering from brain tumor, prognosis estimation and treatment decisions are made by a multidisciplinary team based on a set of preoperative MR scans. Currently, the lack of standardized and automatic methods for tumor detection and generation of clinical reports, incorporating a wide range of tumor characteristics, represents a major hurdle. In this study, we investigate the most occurring brain tumor types: glioblastomas, lower grade gliomas, meningiomas, and metastases, through four cohorts of up to 4,000 patients. Tumor segmentation models were trained using the AGU-Net architecture with different preprocessing steps and protocols. Segmentation performances were assessed in-depth using a wide-range of voxel and patient-wise metrics covering volume, distance, and probabilistic aspects. Finally, two software solutions have been developed, enabling an easy use of the trained models and standardized generation of clinical reports: Raidionics and Raidionics-Slicer. Segmentation performances were quite homogeneous across the four different brain tumor types, with an average true positive Dice ranging between 80 and 90%, patient-wise recall between 88 and 98%, and patient-wise precision around 95%. In conjunction to Dice, the identified most relevant other metrics were the relative absolute volume difference, the variation of information, and the Hausdorff, Mahalanobis, and object average symmetric surface distances. With our Raidionics software, running on a desktop computer with CPU support, tumor segmentation can be performed in 16-54 s depending on the dimensions of the MRI volume. For the generation of a standardized clinical report, including the tumor segmentation and features computation, 5-15 min are necessary. All trained models have been made open-access together with the source code for both software solutions and validation metrics computation. In the future, a method to convert results from a set of metrics into a final single score would be highly desirable for easier ranking across trained models. In addition, an automatic classification of the brain tumor type would be necessary to replace manual user input. Finally, the inclusion of post-operative segmentation in both software solutions will be key for generating complete post-operative standardized clinical reports.
49.	De Glind, GV, et al. (author) The International ADHD in Substance Use Disorders Prevalence (IASP) study: background, methods and study population 2013 In: International journal of methods in psychiatric research. - : Wiley. - 1557-0657 .- 1049-8931. ; 22:3, s. 232-244 Journal article (peer-reviewed)
50.	Guiraud, J., et al. (author) Treating alcohol dependence with an abuse and misuse deterrent formulation of sodium oxybate: Results of a randomised, double-blind, placebo-controlled study 2021 In: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X. ; 52, s. 18-30 Journal article (peer-reviewed)abstract Sodium oxybate (SMO) has been approved in Italy and Austria for the maintenance of abstinence in alcohol dependent (AD) patients. Although SMO is well tolerated in AD patients, cases of abuse and misuse have been reported outside the therapeutic setting. Here we report on a phase IIb double-blind, randomized, placebo-controlled trial for the maintenance of abstinence in AD patients with a new abuse and misuse deterrent formulation of SMO. A total of 509 AD patients were randomized to 12 weeks of placebo or one of four SMO doses (0.75, 1.25, 1.75 or 2.25 g t.i.d.) followed by a one-week medication-free period. The primary endpoint was the percentage of days abstinent (PDA) at end of treatment. An unexpectedly high placebo response (mean 73%, median 92%) was observed. This probably compromised the demonstration of efficacy in the PDA, but several secondary endpoints showed statistically significant improvements. A post-hoc subgroup analysis based on baseline severity showed no improvements in the mild group, but statistically significant improvements in the severe group: PDA: mean difference +15%, Cohen's d = 0.42; abstinence: risk difference +18%, risk ratio = 2.22. No safety concerns were reported. Although the primary endpoint was not significant in the overall population, several secondary endpoints were significant in the intent-to-treat population and post-hoc results showed that treatment with SMO was associated with a significant improvement in severe AD patients which is consistent with previous findings. New trials are warranted that take baseline severity into consideration. (C) 2021 The Authors. Published by Elsevier B.V.

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