High-performance, non-target, high-resolution organic structural spectroscopy was applied to solid phase extracted marine dissolved organic matter (SPE-DOM) isolated from four different depths in the ...open South Atlantic Ocean off the Angola coast (3° E, 18° S; Angola Basin) and provided molecular level information with extraordinary coverage and resolution. Sampling was performed at depths of 5 m (Angola Current; near-surface photic zone), 48 m (Angola Current; fluorescence maximum), 200 m (still above Antarctic Intermediate Water, AAIW; upper mesopelagic zone) and 5446 m (North Atlantic Deep Water, NADW; abyssopelagic, ~30 m above seafloor) and produced SPE-DOM with near 40% carbon yield and beneficial nuclear magnetic resonance (NMR) relaxation properties, a crucial prerequisite for the acquisition of NMR spectra with excellent resolution. 1H and 13C NMR spectra of all four marine SPE-DOM showed smooth bulk envelopes, reflecting intrinsic averaging from massive signal overlap, with a few percent of visibly resolved signatures and variable abundances for all major chemical environments. The abundance of singly oxygenated aliphatics and acetate derivatives in 1H NMR spectra declined from surface to deep marine SPE-DOM, whereas C-based aliphatics and carboxyl-rich alicyclic molecules (CRAM) increased in abundance. Surface SPE-DOM contained fewer methyl esters than all other samples, likely a consequence of direct exposure to sunlight. Integration of 13C NMR spectra revealed continual increase of carboxylic acids and ketones from surface to depth, reflecting a progressive oxygenation, with concomitant decline of carbohydrate-related substructures. Aliphatic branching increased with depth, whereas the fraction of oxygenated aliphatics declined for methine, methylene and methyl carbon. Lipids in the oldest SPE-DOM at 5446 m showed a larger share of ethyl groups and methylene carbon than observed in the other samples. Two-dimensional NMR spectra showed exceptional resolution and depicted resolved molecular signatures in excess of a certain minimum abundance. Classical methyl groups terminating aliphatic chains represented ~15% of total methyl in all samples investigated. A noticeable fraction of methyl (~2%) was bound to olefinic carbon. Methyl ethers were abundant in surface marine SPE-DOM, and the chemical diversity of carbohydrates was larger than that of freshwater and soil DOM. In all samples, we identified sp2-hybridized carbon chemical environments with discrimination of isolated and conjugated olefins and α,β-unsaturated double bonds. Olefinic proton and carbon atoms were more abundant than aromatic ones; olefinic unsaturation in marine SPE-DOM will be more directly traceable to ultimate biogenic precursors than aromatic unsaturation. The abundance of furan, pyrrol and thiophene derivatives was marginal, whereas benzene derivatives, phenols and six-membered nitrogen heterocycles were prominent; a yet unassigned set of six-membered N-heterocycles with likely more than one single nitrogen occurred in all samples. Various key polycyclic aromatic hydrocarbon substructures suggested the presence of thermogenic organic matter at all water depths. Progressive NMR cross-peak attenuation from surface to deep marine SPE-DOM was particularly strong in COSY NMR spectra and indicated a continual disappearance of biosignatures as well as entropy gain from an ever increased molecular diversity. Nevertheless, a specific near-seafloor SPE-DOM signature of unsaturated molecules recognized in both NMR and Fourier transform ion cyclotron mass spectrometry (FTICR/MS) possibly originated from sediment leaching. The conformity of key NMR and FTICR/MS signatures suggested the presence of a large set of identical molecules throughout the entire ocean column even though the investigated water masses belonged to different oceanic regimes and currents. FTICR/MS showed abundant CHO, CHNO, CHOS and CHNOS molecular series with slightly increasing numbers of mass peaks and average mass from surface to bottom SPE-DOM. The proportion of CHO and CHNO negative ions increased from surface to depth, whereas CHOS and especially CHNOS molecular series markedly declined. While certain rather aliphatic CHOS and CHNOS ions were observed solely in the surface, deep marine SPE-DOM was enriched in unique unsaturated and rather oxygenated CHO and CHNO molecular series. With the exception of abyssopelagic SPE-DOM at 5446 m, which showed a peculiar CHOS chemistry of unsaturated carbon and reduced sulphur (black sulphur), CHO and CHNO molecular series contributed ~87% to total positive electrospray ionization FTICR mass peak integral, with a near constant ratio of CHNO / CHO molecular compositions near 1.13 ± 0.05. In case of all four marine SPE-DOM, remarkably disparate average elemental compositions as determined from either MS and NMR spectra were observed, caused by a pronounced ionization selectivity in electrospray ionization FTICR/MS. The study demonstrates that the exhaustive characterization of complex unknowns in marine DOM will enable a meaningful classification of individual marine biogeosignatures. Future in-depth functional biodiversity studies with a clear understanding of DOM structure and function might eventually lead to a novel, unified perception of biodiversity and biogeochemistry.
Critically ill patients undergo extensive physiological alterations that will have impact on antibiotic pharmacokinetics. Up to 60% of intensive care unit (ICU) patients meet the pharmacodynamic ...targets of beta-lactam antibiotics, with only 30% in fluoroquinolones. Not reaching these targets might increase the chance of therapeutic failure, resulting in increased mortality and morbidity, and antibiotic resistance. The DOLPHIN trial was designed to demonstrate the added value of therapeutic drug monitoring (TDM) of beta-lactam and fluoroquinolones in critically ill patients in the ICU.
A multi-centre, randomised controlled trial (RCT) was designed to assess the efficacy and cost-effectiveness of model-based TDM of beta-lactam and fluoroquinolones. Four hundred fifty patients will be included within 24 months after start of inclusion. Eligible patients will be randomly allocated to either study group: the intervention group (active TDM) or the control group (non-TDM). In the intervention group dose adjustment of the study antibiotics (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, amoxicillin, amoxicillin with clavulanic acid, flucloxacillin, piperacillin with tazobactam, meropenem, and ciprofloxacin) on day 1, 3, and 5 is performed based upon TDM with a Bayesian model. The primary outcome will be ICU length of stay. Other outcomes amongst all survival, disease severity, safety, quality of life after ICU discharge, and cost effectiveness will be included.
No trial has investigated the effect of early TDM of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients. The findings from the DOLPHIN trial will possibly lead to new insights in clinical management of critically ill patients receiving antibiotics. In short, to TDM or not to TDM?
EudraCT number: 2017-004677-14. Sponsor protocol name: DOLPHIN. Registered 6 March 2018 . Protocol Version 6, Protocol date: 27 November 2019.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention, hyperactivity, and impulsivity. It is the most common ...neurodevelopmental disorder presenting to pediatric services, and pediatricians are often involved in the early assessment, diagnosis, and treatment of children with ADHD. The treatment of ADHD typically involves a multimodal approach that encompasses a combination of psychoeducation, parent/teacher training, psychosocial/psychotherapeutic interventions, and pharmacotherapy. Concerning pharmacotherapy, guidelines vary in drug choice and sequencing, with psychostimulants, such as methylphenidate and (lis)dexamfetamine, generally being the favored initial treatment. Alternatives include atomoxetine and guanfacine. Pharmacotherapy has been proven effective, but close follow-up focusing on physical growth, cardiovascular monitoring, and the surveillance of potential side effects including tics, mood fluctuations, and psychotic symptoms, is essential. This paper presents an overview of current pharmacological treatment options for ADHD and explores disparities in treatment guidelines across different European countries.
Conclusion
: Pharmacological treatment options for ADHD in children and adolescents are effective and generally well-tolerated. Pharmacotherapy for ADHD is always part of a multimodal approach. While there is a considerable consensus among European guidelines on pharmacotherapy for ADHD, notable differences exist, particularly concerning the selection and sequencing of various medications.
What is Known:
• There is a significant base of evidence for pharmacological treatment for ADHD in children and adolescents.
• Pediatricians are often involved in assessment, diagnosis and management of children with ADHD.
What is New:
• Our overview of different European guidelines reveals significant agreement in the context of pharmacotherapy for ADHD in children and adolescents.
• Discrepancies exist primarily in terms of selection and sequencing of different medications.
The degradation of marine dissolved organic matter (DOM) is an important control variable in the global carbon cycle. For our understanding of the kinetics of organic matter cycling in the ocean, it ...is crucial to achieve a mechanistic and molecular understanding of its transformation processes. A long-term microbial experiment was performed to follow the production of non-labile DOM by marine bacteria. Two different glucose concentrations and dissolved algal exudates were used as substrates. We monitored the bacterial abundance, concentrations of dissolved and particulate organic carbon (DOC, POC), nutrients, amino acids and transparent exopolymer particles (TEP) for 2 years. The molecular characterization of extracted DOM was performed by ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) after 70 days and after ∼2 years of incubation. Although glucose quickly degraded, a non-labile DOC background (5–9% of the initial DOC) was generated in the glucose incubations. Only 20% of the organic carbon from the algal exudate degraded within the 2 years of incubation. The degradation rates for the non-labile DOC background in the different treatments varied between 1 and 11 μmol DOC L−1 year−1. Transparent exopolymer particles, which are released by microorganisms, were produced during glucose degradation but decreased back to half of the maximum concentration within less than 3 weeks (degradation rate: 25 μg xanthan gum equivalents L−1 d−1) and were below detection in all treatments after 2 years. Additional glucose was added after 2 years to test whether labile substrate can promote the degradation of background DOC (co-metabolism; priming effect). A priming effect was not observed but the glucose addition led to a slight increase of background DOC. The molecular analysis demonstrated that DOM generated during glucose degradation differed appreciably from DOM transformed during the degradation of the algal exudates. Our results led to several conclusions: (i) based on our experimental setup, higher substrate concentration resulted in a higher concentration of non-labile DOC; (ii) TEP, generated by bacteria, degrade rapidly, thus limiting their potential contribution to carbon sequestration; (iii) the molecular signatures of DOM derived from algal exudates and glucose after 70 days of incubation differed strongly from refractory DOM. After 2 years, however, the molecular patterns of DOM in glucose incubations were more similar to deep ocean DOM whereas the degraded exudate was still different.
Estimates of forest biomass are needed for various technical and scientific applications, ranging from carbon and bioenergy policies to sustainable forest management. As local measurements are ...costly, there is a great interest in obtaining reliable estimates over large areas from remote sensing data. Currently, such estimates are obtained with a variety of data sources, statistical methods and prediction standards, and there is no agreement on what are best practices for this task.
To improve our understanding of how these different methods affect prediction quality, we first conducted a systematic review of the available literature to identify the most common sensor types and prediction methods. Based on the review, we identified sample size of the reference points on the ground, prediction method (stepwise linear regression, support vector machines, random forest, Gaussian processes and k-nearest neighbor), and sensor type as the main differences that could potentially affect predictive quality. We then compared those factors in two case study areas in Germany and Chile, for which airborne discrete return Light Detection And Ranging (LiDAR) and airborne hyperspectral as well as airborne discrete return LiDAR and spaceborne hyperspectral data were available. For each factor combination, we calculated Pearson's coefficient of correlation between observations and predictions (r2) and root mean squared error (RMSE) for bootstrapped estimates using k-fold cross-validation with a varying number of folds. Finally, Analysis of Variance (ANOVA) was used to quantify the influence of the factors on the predictive error of the biomass models.
Our results confirm previous findings that predictor data (sensor) type is the most important factor for the accuracy of biomass estimates, with LiDAR being preferable to hyperspectral data. In contrast to some previous studies, complementing LiDAR with hyperspectral data did not improve predictive accuracy. Also the prediction method had a substantial effect on accuracy and was generally more important than the sample size. In most cases, random forest performed best and stepwise linear models worst, judging from r2 and RMSE under cross-validation. Additional results suggested that r2 may deliver unrealistically large values when the hold-out sample during the cross-validation is too small.
In conclusion, our literature review revealed that different methods for biomass estimation are currently used, with no general agreement on best practices. In our case studies, we found substantial accuracy differences between those methods, with LiDAR data, in combination with a random forest algorithm and a large number of reference sample units on the ground yielding the lowest error for biomass predictions. The comparatively high importance of the statistical prediction method seems particularly relevant, as they suggest that choosing the appropriate statistical method may be more effective than obtaining additional field data for obtaining good biomass estimates. Considering the costs of improving accuracy of global and regional biomass estimates by ground measurements, it seems sensible to invest in further comparative studies, preferably with a wider range of sites and including also RADAR sensors, to establish robust best-practice recommendations for obtaining regional and global biomass estimates from remote-sensing data.
•Methods for modeling forest biomass were identified via a systematic review.•We applied hyperspectral and LiDAR to model aboveground forest biomass.•We examined the influence of the statistical model set-up on biomass models.•Sensor type and prediction method had notable influences on model performances.•Random forest in combination with LiDAR data and many samples performed best.
In this work, a novel mechanism for spontaneous symmetry breaking is presented. This mechanism incorporates gravity in the generation of masses for gauge fields, showing that the Higgs mechanism can ...take place even without a quartic self-interaction at the fundamental level. Using the scale-dependent effective action Γk minimally coupled to a gravitational sector, a variational parameter setting is applied. This provides a mass and vacuum expectation value as a function of the constants arising in the low-scale expansion of Newton and cosmological couplings. A comparison with experimental data, such as the Higgs mass, allows putting restrictions on these constants. This generic approach can be compared with explicit candidates for an effective field theory of gravity. As an example, we use the asymptotic safety scenario, where we find restrictions on the matter content of the theory.
Soils, sediments, freshwaters, and marine waters contain natural organic matter (NOM), an exceedingly complex mixture of organic compounds that collectively exhibit a nearly continuous range of ...properties (size-reactivity continuum). NOM is composed mainly of carbon, hydrogen, and oxygen, with minor contributions from heteroatoms such as nitrogen, sulfur, and phosphorus. Suwannee River fulvic acid (SuwFA) is a fraction of NOM that is relatively depleted in heteroatoms. Ultrahigh resolution Fourier transform ion cyclotron (FTICR) mass spectra of SuwFA reveal several thousand molecular formulas, corresponding in turn to several hundred thousand distinct chemical environments of carbon even without accountancy of isomers. The mass difference Δm among adjoining C,H,O-molecules between and within clusters of nominal mass is inversely related to molecular dissimilarity: any decrease of Δm imposes an ever growing mandatory difference in molecular composition. Molecular formulas that are expected for likely biochemical precursor molecules are notably absent from these spectra, indicating that SuwFA is the product of diagenetic reactions that have altered the major components of biomass beyond the point of recognition. The degree of complexity of SuwFA can be brought into sharp focus through comparison with the theoretical limits of chemical complexity, as constrained and quantized by the fundamentals of chemical binding. The theoretical C,H,O-compositional space denotes the isomer-filtered complement of the entire, very vast space of molecular structures composed solely of carbon, hydrogen, and oxygen. The molecular formulas within SuwFA occupy a sizable proportion of the theoretical C,H,O-compositional space. A 100 percent coverage of the theoretically feasible C,H,O-compositional space by SuwFA molecules is attained throughout a sizable range of mass and H/C and O/C elemental ratios. The substantial differences between (and complementarity of) the SuwFA molecular formulas that are observed using six different modes of ionization (APCI, APPI, and ESI in positive and negative modus) imply considerable selectivity of the ionization process and suggest that the observed mass spectra represent simplified projections of still more complex mixtures.
We study the quantum gravity modification of the Kuroda-Papapetrou model induced by the running of the Newton's constant at high energy in quantum Einstein gravity. We argue that although the ...antiscreening character of the gravitational interaction favours the formation of a naked singularity, quantum gravity effects turn the classical singularity into a 'whimper' singularity which remains naked for a finite amount of advanced time.
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