Adults with attention‐deficit/hyperactivity disorder (ADHD) have been described as having altered resting‐state electroencephalographic (EEG) spectral power and theta/beta ratio (TBR). However, a ...recent review (Pulini et al. 2018) identified methodological errors in neuroimaging, including EEG, ADHD classification studies. Therefore, the specific EEG neuromarkers of adult ADHD remain to be identified, as do the EEG characteristics that mediate between genes and behaviour (mediational endophenotypes). Resting‐state eyes‐open and eyes‐closed EEG was measured from 38 adults with ADHD, 45 first‐degree relatives of people with ADHD and 51 unrelated controls. A machine learning classification analysis using penalized logistic regression (Elastic Net) examined if EEG spectral power (1–45 Hz) and TBR could classify participants into ADHD, first‐degree relatives and/or control groups. Random‐label permutation was used to quantify any bias in the analysis. Eyes‐open absolute and relative EEG power distinguished ADHD from control participants (area under receiver operating characteristic = 0.71–0.77). The best predictors of ADHD status were increased power in delta, theta and low‐alpha over centro‐parietal regions, and in frontal low‐beta and parietal mid‐beta. TBR did not successfully classify ADHD status. Elevated eyes‐open power in delta, theta, low‐alpha and low‐beta distinguished first‐degree relatives from controls (area under receiver operating characteristic = 0.68–0.72), suggesting that these features may be a mediational endophenotype for adult ADHD. Resting‐state EEG spectral power may be a neuromarker and mediational endophenotype of adult ADHD. These results did not support TBR as a diagnostic neuromarker for ADHD. It is possible that TBR is a characteristic of childhood ADHD.
Machine learning classification analysis with penalized logistic regression revealed specific eyes‐open resting‐state EEG spectral power neuromarkers for adults with attention‐deficit/hyperactivity disorder (ADHD). These can be developed and integrated into complementary assessment/prognostic tools for adult ADHD diagnostics. We also found specific EEG characteristics that mediate between genes and behaviour. Our results did not support theta/beta ratio as a diagnostic neuromarker for adult ADHD.
Evolution and applications of the QuEChERS method González-Curbelo, M.Á.; Socas-Rodríguez, B.; Herrera-Herrera, A.V. ...
TrAC, Trends in analytical chemistry (Regular ed.),
09/2015, Letnik:
71
Journal Article
Recenzirano
•QuECHERS (quick, easy, cheap, effective, rugged, and safe) method for analysis.•QuECHERS is the most frequent sample pretreatment in residue laboratories.•QuECHERS applied for the extraction of a ...wide diversity of analytes and matrices.•Modified QuECHERS improved recoveries, and avoided degradation and matrix effects.•QuEChERS has mainly been combined with LC-MS and GC-MS.
It is widely recognized that the QuEChERS (quick, easy, cheap, effective, rugged, and safe) method is relevant in pesticide residue analysis. Many official laboratories around the globe are routinely using it due to the advantages encapsulated in its name. However, the frontiers of the application of QuEChERS are not yet established. The method is effective for the analysis of other groups of compounds, including pharmaceuticals, mycotoxins, and polycyclic aromatic hydrocarbons, in a wide variety of complex matrices. This review article provides a general overview of the most relevant modifications of the QuEChERS method that have been widely accepted and applied (including both extraction and clean-up) and a general view of the different groups of compounds to which it has been fruitfully applied. We do not include those approaches where only half the method has been used.
Severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) has caused substantially more infections, deaths, and economic disruptions than the 2002‐2003 SARS‐CoV. The key to understanding ...SARS‐CoV‐2's higher infectivity lies partly in its host receptor recognition mechanism. Experiments show that the human angiotensin converting enzyme 2 (ACE2) protein, which serves as the primary receptor for both CoVs, binds to the receptor binding domain (RBD) of CoV‐2's spike protein stronger than SARS‐CoV's spike RBD. The molecular basis for this difference in binding affinity, however, remains unexplained from X‐ray structures. To go beyond insights gained from X‐ray structures and investigate the role of thermal fluctuations in structure, we employ all‐atom molecular dynamics simulations. Microseconds‐long simulations reveal that while CoV and CoV‐2 spike‐ACE2 interfaces have similar conformational binding modes, CoV‐2 spike interacts with ACE2 via a larger combinatorics of polar contacts, and on average, makes 45% more polar contacts. Correlation analysis and thermodynamic calculations indicate that these differences in the density and dynamics of polar contacts arise from differences in spatial arrangements of interfacial residues, and dynamical coupling between interfacial and non‐interfacial residues. These results recommend that ongoing efforts to design spike‐ACE2 peptide blockers will benefit from incorporating dynamical information as well as allosteric coupling effects.
Perylene tetracarboxylic diimide (PTCDI) derivatives stand out as one of the most investigated families of air-stable n-type organic semiconductors for organic thin-film transistors. Here, we use ...density functional theory to illustrate how it is possible to control the charge-transport parameters of PTCDIs as a function of the type, number, and positions of the substituents. Specifically, two strategies of functionalization related to core and end substitutions are investigated. While end-substituted PTCDIs present the same functional molecular backbone, their molecular packing in the crystal significantly varies; as a consequence, this series of derivatives constitutes an ideal test bed to evaluate the models that describe charge-transport in organic semiconductors. Our results indicate that large bandwidths along with small effective masses can be obtained with the insertion of appropriate substituents on the nitrogens, in particular halogenated aromatic groups.
Lafora disease is a fatal neurodegenerative condition characterized by the accumulation of abnormal glycogen inclusions known as Lafora bodies. It is an autosomal recessive disorder caused by ...mutations in either the laforin or malin gene. To study whether glycogen is primarily responsible for the neurodegeneration in Lafora disease, we generated malin knockout mice with impaired (totally or partially) glycogen synthesis. These animals did not show the increase in markers of neurodegeneration, the impairments in electrophysiological properties of hippocampal synapses, nor the susceptibility to kainate-induced epilepsy seen in the malin knockout model. Interestingly, the autophagy impairment that has been described in malin knockout animals was also rescued in this double knockout model. Conversely, two other mouse models in which glycogen is over-accumulated in the brain independently of the lack of malin showed impairment in autophagy. Our findings reveal that glycogen accumulation accounts for the neurodegeneration and functional consequences seen in the malin knockout model, as well as the impaired autophagy. These results identify the regulation of glycogen synthesis as a key target for the treatment of Lafora disease.
To evaluate published evidence of efficacy and safety of pharmacologic treatments for childhood spasticity due to cerebral palsy.
A multidisciplinary panel systematically reviewed relevant literature ...from 1966 to July 2008.
For localized/segmental spasticity, botulinum toxin type A is established as an effective treatment to reduce spasticity in the upper and lower extremities. There is conflicting evidence regarding functional improvement. Botulinum toxin type A was found to be generally safe in children with cerebral palsy; however, the Food and Drug Administration is presently investigating isolated cases of generalized weakness resulting in poor outcomes. No studies that met criteria are available on the use of phenol, alcohol, or botulinum toxin type B injections. For generalized spasticity, diazepam is probably effective in reducing spasticity, but there are insufficient data on its effect on motor function and its side-effect profile. Tizanidine is possibly effective, but there are insufficient data on its effect on function and its side-effect profile. There were insufficient data on the use of dantrolene, oral baclofen, and intrathecal baclofen, and toxicity was frequently reported.
For localized/segmental spasticity that warrants treatment, botulinum toxin type A should be offered as an effective and generally safe treatment (Level A). There are insufficient data to support or refute the use of phenol, alcohol, or botulinum toxin type B (Level U). For generalized spasticity that warrants treatment, diazepam should be considered for short-term treatment, with caution regarding toxicity (Level B), and tizanidine may be considered (Level C). There are insufficient data to support or refute use of dantrolene, oral baclofen, or continuous intrathecal baclofen (Level U).
Star formation driven galactic winds in UGC 10043 López-Cobá, C; Sánchez, S. F; Moiseev, A. V ...
Monthly notices of the Royal Astronomical Society,
06/2017, Letnik:
467, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Abstract
We study the galactic wind in the edge-on spiral galaxy UGC 10043 with the combination of the CALIFA integral field spectroscopy data, scanning Fabry–Perot interferometry (FPI) and multiband ...photometry. We detect ionized gas in the extraplanar regions reaching a relatively high distance, up to ∼4 kpc above the galactic disc. The ionized gas line ratios (N ii/Hα, S ii/Hα and O i/Hα) present an enhancement along the semiminor axis, in contrast with the values found at the disc, where they are compatible with ionization due to H ii-regions. These differences, together with the biconic symmetry of the extra-planar ionized structure, make UGC 10043 a clear candidate for a galaxy with gas outflows ionizated by shocks. From the comparison of shock models with the observed line ratios, and the kinematics observed from the FPI data, we constrain the physical properties of the observed outflow. The data are compatible with a velocity increase of the gas along the extraplanar distances up to <400 km s−1 and the pre-shock density decreasing in the same direction. We also observe a discrepancy in the SFR estimated based on Hα (0.36 M⊙ yr−1) and that estimated with the cigale code, the latter being five times larger. Nevertheless, this SFR is still not enough to drive the observed galactic wind if we do not take into account the filling factor. We stress that the combination of the three techniques of observation with the models is a powerful tool to explore galactic winds in the Local Universe.
Fracton models provide examples of novel gapped quantum phases of matter that host intrinsically immobile excitations and therefore lie beyond the conventional notion of topological order. Here, we ...calculate optimal error thresholds for quantum error correcting codes based on fracton models. By mapping the error-correction process for bit-flip and phase-flip noises into novel statistical models with Ising variables and random multibody couplings, we obtain models that exhibit an unconventional subsystem symmetry instead of a more usual global symmetry. We perform large-scale parallel tempering Monte Carlo simulations to obtain disorder-temperature phase diagrams, which are then used to predict optimal error thresholds for the corresponding fracton code. Remarkably, we found that the X-cube fracton code displays a minimum error threshold (7.5%) that is much higher than 3D topological codes such as the toric code (3.3%), or the color code (1.9%). This result, together with the predicted absence of glass order at the Nishimori line, shows great potential for fracton phases to be used as quantum memory platforms.
•Prediction of nutrient fertility indices in three districts of Maharashtra (India).•Soil nutrients include organic carbon, phosphorus, iron, manganese and zinc.•We apply 76 regression methods of 20 ...regressor families.•The extremely randomized trees achieve the best results, except for organic carbon.•Correlations between 0.75 and 0.83, depending on the nutrient, are achieved.
In low quality soils, as in the Indian state of Maharashtra, a sustainable land management practice is very important to enhance the soil quality and to maintain proper values for several nutrients that are relevant for an optimal crop yield. The evaluation of a soil fertility index for these nutrients and for each geographical place allows to create maps of village-wise fertility indices which are very useful for fertility management. An automatic prediction of such fertility indices would be very important to reduce the amount of chemical measurements of nutrients to be performed in different cultivation lands. The current study develops the prediction of fertility indices for soil organic carbon and four important soil nutrients (phosphorus pentoxide, iron, manganese and zinc) using almost all the available regression methods, specifically a collection of 76 regressors which belong to 20 families, including neural networks, deep learning, support vector regression, random forests, bagging and boosting, lasso and ridge regression, Bayesian models and more. The best results are achieved by the extremely randomized regression trees (extraTrees), with which achieve an acceptable prediction accuracy (average squared correlations between 0.57 and 0.70), being also relatively fast. Other regressors with high performance are random forests and regularized random forest, generalized boosting regression model and epsilon-support vector regression.
Biosimilar medicines expand the biotherapeutic market and improve patient access. This work looked into the landscape of the European and US biosimilar products, their regulatory authorization, ...market availability, and clinical evaluation undergone prior to the regulatory approval. European Medicines Agency (EMEA, currently EMA) and Food and Drug Administration (FDA) repositories were searched to identify all biosimilar medicines approved before December 2019. Adalimumab biosimilars, and particularly their clinical evaluations, were used as a case study. In the past 13 years, the EMA has received 65 marketing authorization applications for biosimilar medicines with 55 approved biosimilars available in the EU market. Since the first biosimilar approval in 2015, the FDA has granted 26 approvals for biosimilars with only 11 being currently on the US market. Five adalimumab biosimilars have been approved in the EU and commercialized as eight different medicines through duplicate marketing authorizations. Whilst three of these are FDA-approved, the first adalimumab biosimilar will not be marketed in the US until 2023 due to Humira's exclusivity period. The EU biosimilar market has developed faster than its US counterpart, as the latter is probably challenged by a series of patents and exclusivity periods protecting the bio-originator medicines, an issue addressed by the US's latest 'Biosimilar Action Plan'.
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