The occurrence and spatial distribution of 158 pharmaceuticals and drugs of abuse were studied in seawater of the Eastern Mediterranean Sea (Saronikos Gulf and Elefsis Bay in central Aegean Sea). ...This area is affected by various anthropogenic pressures as it receives the treated wastewater of the greatest Athens area and off-shore input fluxes. This study constitutes the largest one in terms of number of analytes in this environmental compartment. It provides the first evidence on the occurrence of several pharmaceuticals in marine environment including amoxicillin, lidocaine, citalopram or tramadol, among others.
22 samples were collected at three different depths in 9 sampling stations in order to assess the presence and the spatial distribution of the target compounds. A multi-residue method based on solid phase extraction and liquid chromatography coupled to tandem mass spectrometry was developed for the determination of the 158 target substances and validated for seawater sample analysis. 38 out of the 158 target compounds were detected, 15 of them with frequencies of detection equal to or higher than 50%. The highest detected values corresponded to amoxicillin, caffeine and salicylic acid, with concentrations in the range of <5.0–127.8ngL−1; 5.2–78.2ngL−1 and <0.4–53.3ngL−1, respectively. Inputs from the wastewater treatment plant (WWTP) of Athens revealed to be the main source of pollution in the Inner Saronikos Gulf, whereas, other anthropogenic pressures such as contamination from shipping activity, industrial effluents, dredging and/or inputs from land proved to be also relevant. Τhe concentrations of some compounds varied significantly with depth suggesting that currents play an important role in the dilution of the target compounds.
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•This is the largest study of emerging contaminants (158) in seawater.•Thirty eight compounds have been detected.•Amoxicillin, salicylic acid and caffeine showed the highest concentration levels.•Wastewater release proved to be the major source of contamination.
Essential to the functionality of qubit-based sensors are control protocols, which shape their response in frequency space. However, in common control routines out-of-band spectral leakage ...complicates interpretation of the sensor's signal. In this work, we leverage discrete prolate spheroidal sequences (a.k.a. Slepian sequences) to synthesize provably optimal narrowband controls ideally suited to spectral estimation of a qubit's noisy environment. Experiments with trapped ions demonstrate how spectral leakage may be reduced by orders of magnitude over conventional controls when a near resonant driving field is modulated by Slepians, and how the desired narrowband sensitivity may be tuned using concepts from RF engineering. We demonstrate that classical multitaper techniques for spectral analysis can be ported to the quantum domain and combined with Bayesian estimation tools to experimentally reconstruct complex noise spectra. We then deploy these techniques to identify previously immeasurable frequency-resolved amplitude noise in our qubit's microwave synthesis chain.
Psychotherapy is successful for the majority of patients, but not for every patient. Hence, further knowledge is needed on how treatments should be adapted for those who do not profit or deteriorate. ...In the last years prediction tools as well as feedback interventions were part of a trend to more personalized approaches in psychotherapy. Research on psychometric prediction and feedback into ongoing treatment has the potential to enhance treatment outcomes, especially for patients with an increased risk of treatment failure or drop-out.
The research project investigates in a randomized controlled trial the effectiveness as well as moderating and mediating factors of psychometric feedback to therapists. In the intended study a total of 423 patients, who applied for a cognitive-behavioral therapy at the psychotherapy clinic of the University Trier and suffer from a depressive and/or an anxiety disorder (SCID interviews), will be included. The patients will be randomly assigned either to one therapist as well as to one of two intervention groups (CG, IG2). An additional intervention group (IG1) will be generated from an existing archival data set via propensity score matching. Patients of the control group (CG; n = 85) will be monitored concerning psychological impairment but therapists will not be provided with any feedback about the patients assessments. In both intervention groups (IG1: n = 169; IG2: n = 169) the therapists are provided with feedback about the patients self-evaluation in a computerized feedback portal. Therapists of the IG2 will additionally be provided with clinical support tools, which will be developed in this project, on the basis of existing systems. Therapists will also be provided with a personalized treatment recommendation based on similar patients (Nearest Neighbors) at the beginning of treatment. Besides the general effectiveness of feedback and the clinical support tools for negatively developing patients, further mediating and moderating variables on this feedback effect should be examined: treatment length, frequency of feedback use, therapist effects, therapist's experience, attitude towards feedback as well as congruence of therapist's and patient's evaluation concerning the progress. Additional procedures will be implemented to assess treatment adherence as well as the reliability of diagnosis and to include it into the analyses.
The current trial tests a comprehensive feedback system which combines precision mental health predictions with routine outcome monitoring and feedback tools in routine outpatient psychotherapy. It also adds to previous feedback research a stricter design by investigating another repeated measurement CG as well as a stricter control of treatment integrity. It also includes a structured clinical interview (SCID) and controls for comorbidity (within depression and anxiety). This study also investigates moderators (attitudes towards, use of the feedback system, diagnoses) and mediators (therapists' awareness of negative change and treatment length) in one study.
Current Controlled Trials NCT03107845 . Registered 30 March 2017.
A molecular basis for memory failure in Alzheimer's disease (AD) has been recently hypothesized, in which a significant role is attributed to small, soluble oligomers of amyloid β-peptide (Aβ). Aβ ...oligomeric ligands (also known as ADDLs) are known to be potent inhibitors of hippocampal long-term potentiation, which is a paradigm for synaptic plasticity, and have been linked to synapse loss and reversible memory failure in transgenic mouse AD models. If such oligomers were to build up in human brain, their neurological impact could provide the missing link that accounts for the poor correlation between AD dementia and amyloid plaques. This article, using antibodies raised against synthetic Aβ oligomers, verifies the predicted accumulation of soluble oligomers in AD frontal cortex. Oligomers in AD reach levels up to 70-fold over control brains. Brain-derived and synthetic oligomers show structural equivalence with respect to mass, isoelectric point, and recognition by conformation-sensitive antibodies. Both oligomers, moreover, exhibit the same striking patterns of attachment to cultured hippocampal neurons, binding on dendrite surfaces in small clusters with ligand-like specificity. Binding assays using solubilized membranes show oligomers to be high-affinity ligands for a small number of nonabundant proteins. Current results confirm the prediction that soluble oligomeric Aβ ligands are intrinsic to AD pathology, and validate their use in new approaches to therapeutic AD drugs and vaccines.
Abnormalities in brain glucose metabolism and accumulation of abnormal protein deposits called plaques and tangles are neuropathological hallmarks of Alzheimer's disease (AD), but their relationship ...to disease pathogenesis and to each other remains unclear. Here we show that succinylation, a metabolism-associated post-translational protein modification (PTM), provides a potential link between abnormal metabolism and AD pathology. We quantified the lysine succinylomes and proteomes from brains of individuals with AD, and healthy controls. In AD, succinylation of multiple mitochondrial proteins declined, and succinylation of small number of cytosolic proteins increased. The largest increases occurred at critical sites of amyloid precursor protein (APP) and microtubule-associated tau. We show that in vitro, succinylation of APP disrupted its normal proteolytic processing thereby promoting Aβ accumulation and plaque formation and that succinylation of tau promoted its aggregation to tangles and impaired microtubule assembly. In transgenic mouse models of AD, elevated succinylation associated with soluble and insoluble APP derivatives and tau. These findings indicate that a metabolism-linked PTM may be associated with AD.
Background
Routine outcome monitoring can support clinicians to detect patients who deteriorate not-on-track (NOT) early in psychotherapy. Implemented Clinical Support Tools can direct clinicians’ ...attention towards potential obstacles to a positive treatment outcome and provide suggestions for suitable interventions. However, few studies have compared NOT patients to patients showing expected progress on-track (OT) regarding such obstacles. This study aimed to identify domains that have predictive value for NOT trajectories and to compare OT and NOT patients regarding these domains and the items of the underlying scales.
Methods
During treatment, 413 outpatients filled in the Hopkins-Symptom-Checklist-11 (depressive and anxious symptom distress) before every therapy session as a routine outcome measure. Further, the Assessment for Signal Clients, Affective Style Questionnaire, and Outcome Questionnaire-30 were applied every fifth session. These questionnaires measure the following domains, which were investigated as potential obstacles to treatment success: risk/suicidality, therapeutic alliance, motivation, social support and life events, as well as emotion regulation. Two groups (OT and NOT patients) were formed by defining a cut-off (failure boundary) as the 90% confidence interval (upper bound) of the respective patients’ expected recovery curves. In order to differentiate group membership based on the respective problem areas, multilevel logistic regression analyses were performed. Further, OT and NOT patients were compared with regard to the domains’ and items’ cut-offs by performing Pearson chi-square tests and independent samples
t
-tests.
Results
The life events and motivation scale as well as the risk/suicidality scale proved to be significant predictors of being not-on-track. NOT patients also crossed the cut-off significantly more often on the domains risk/suicidality, social support, and life events. For both OT and NOT patients, the emotion regulation domain’s cut-off was most commonly exceeded.
Conclusion
Life events, motivation, and risk/suicidality seem to be directly linked to treatment failure and should be further investigated for the use in clinical support tools.
TEOSINTE BRANCHED1, CYCLOIDEA, PROLIFERATING CELL FACTOR 1 and 2 (TCP) proteins constitute a plant-specific transcription factors family exerting effects on multiple aspects of plant development, ...such as germination, embryogenesis, leaf and flower morphogenesis, and pollen development, through the recruitment of other factors and the modulation of different hormonal pathways. They are divided into two main classes, I and II. This review focuses on the function and regulation of class I TCP proteins (TCPs). We describe the role of class I TCPs in cell growth and proliferation and summarize recent progresses in understanding the function of class I TCPs in diverse developmental processes, defense, and abiotic stress responses. In addition, their function in redox signaling and the interplay between class I TCPs and proteins involved in immunity and transcriptional and posttranslational regulation is discussed.
We characterize the dynamical behavior of continuous-time, Markovian quantum systems with respect to a subsystem of interest. Markovian dynamics describes a wide class of open quantum systems of ...relevance to quantum information processing, subsystem encodings offering a general pathway to faithfully represent quantum information. We provide explicit linear-algebraic characterizations of the notion of invariant and noiseless subsystem for Markovian master equations, under different robustness assumptions for model-parameter and initial-state variations. The stronger concept of an attractive quantum subsystem is introduced, and sufficient existence conditions are identified based on Lyapunov's stability techniques. As a main control application, we address the potential of output-feedback Markovian control strategies for quantum pure state-stabilization and noiseless-subspace generation. In particular, explicit results for the synthesis of stabilizing semigroups and noiseless subspaces in finite-dimensional Markovian systems are obtained.
The high Nb containing TiAl based alloy, Ti–46Al–9Nb (at.%), was produced using accumulative roll bonding (ARB) followed by two-stage reaction annealing from Ti, Al, and Nb elemental foils. ...Well-bonded sheet materials were successfully obtained with an initial rolling reduction of 50%. Two-stage annealing of 600 and 1400
°C was employed to promote the formation of intermetallic compounds. The cooling rate was controlled to produce the lamellar structure. The scanning electron microscopy and X-ray diffraction indicated that there were no room temperature solid-state reactions between the Ti/Al/Nb foils, even at 10 cycles. Besides the annealing time and temperature, rolling strain also has a significant effect on the production of the intermetallic compound. Differential thermal analysis was used to characterize the effect of rolling strain on the solid-state reaction and phase formation in the composites during annealing. It is clear that the first annealing stage produced a complete reaction of the Al layers forming the intermetallic compounds TiAl
3 and NbAl
3. The desired composition and structure of the intermetallic compounds were achieved after the second stage annealing.
•The risk due to 207 ECs contained in wastewater was evaluated in country level.•RQ>1 were calculated for 30 compounds in secondary treated wastewater.•The mixture of ECs possessed serious ...environmental risk to all studied rivers.•Among different groups, endocrine disrupters seem to pose the highest risk.•Measures related to the updating of legislation and STPs upgrading should be taken.
The ecological threat associated with emerging pollutants detected in wastewater was estimated in country level. Treated wastewater was analyzed for pharmaceuticals and illicit drugs; whereas the concentrations of all emerging contaminants determined in Greek Sewage Treatment Plants were recorded through literature review. Toxicity data was collected after literature review or using ECOSAR and risk quotients (RQs) were calculated for treated wastewater and 25 Greek rivers, for 3 different aquatic organisms (fish, daphnia magna, algae). According to the results, monitoring data was available for 207 micropollutants belonging to 8 different classes. RQ>1 was calculated for 30 compounds in secondary treated wastewater. Triclosan presented RQ>1 (in algae) for all studied rivers; decamethylcyclopentasilane (in daphnia magna), caffeine (in algae) and nonylphenol (in fish) presented RQ>1 in rivers with dilution factors (DF) equal or lower to 1910, 913 and 824, respectively. The class of emerging contaminants that present the greatest threat due to single or mixture toxicity was endocrine disrupters. The mixture of microcontaminants seems to pose significant ecological risk, even in rivers with DF equal to 2388. Future national monitoring programs should include specific microcontaminants that seem to possess environment risk to surface water.
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