The combination of chemo- and photocatalyses with biocatalysis, which couples the flexible reactivity of the photo- and chemocatalysts with the highly selective and environmentally friendly nature of ...enzymes in one-pot linear cascades, represents a powerful tool in organic synthesis. However, the combination of photo-, chemo- and biocatalysts in one-pot is challenging because the optimal operating conditions of the involved catalyst types may be rather different, and the different stabilities of catalysts and their mutual deactivation are additional problems often encountered in one-pot cascade processes. This review explores a large number of transformations and approaches adopted for combining enzymes and chemo- and photocatalytic processes in a successful way to achieve valuable chemicals and valorisation of biomass. Moreover, the strategies for solving incompatibility issues in chemo-enzymatic reactions are analysed, introducing recent examples of the application of non-conventional solvents, enzyme–metal hybrid catalysts, and spatial compartmentalization strategies to implement chemo-enzymatic cascade processes.
Nasal obstruction (NO) is defined as the subjective perception of discomfort or difficulty in the passage of air through the nostrils. It is a common reason for consultation in primary and ...specialized care and may affect up to 30%-40% of the population. It affects quality of life (especially sleep) and lowers work efficiency. The aim of this document is to agree on how to treat NO, establish a methodology for evaluating and diagnosing it, and define an individualized approach to its treatment. NO can be unilateral or bilateral, intermittent or persistent and may be caused by local or systemic factors, which may be anatomical, inflammatory, neurological, hormonal, functional, environmental, or pharmacological in origin. Directed study of the medical history and physical examination are key for diagnosing the specific cause. NO may be evaluated using subjective assessment tools (visual analog scale, symptom score, standardized questionnaires) or by objective estimation (active anterior rhinomanometry, acoustic rhinometry, peak nasal inspiratory flow). Although there is little correlation between the results, they may be considered complementary and not exclusive. Assessing the impact on quality of life through questionnaires standardized according to the underlying disease is also advisable. NO is treated according to its cause. Treatment is fundamentally pharmacological (topical and/or systemic) when the etiology is inflammatory or functional. Surgery may be necessary when medical treatment fails to complement or improve medical treatment or when other therapeutic approaches are not possible. Combinations of surgical techniques and medical treatment may be necessary.
To assess the safety and efficacy of one, two, or three trabecular microbypass stents in eyes with primary open-angle glaucoma (OAG) not controlled on ocular hypotensive medication. A total of 119 ...subjects were followed for 18 months postoperatively.
Subjects with medicated intraocular pressure (IOP) 18-30 mmHg and postmedication-washout baseline IOP 22-38 mmHg were randomized to implantation of one, two, or three stents. Ocular hypotensive medication was to be used if postoperative IOP exceeded 18 mmHg.
A total of 38 subjects were implanted with one stent, 41 subjects with two stents, and 40 subjects with three stents. Both month 12 IOP reduction ≥20% without ocular hypotensive medication vs baseline unmedicated IOP and month 12 unmedicated IOP ≤18 mmHg were achieved by 89.2%, 90.2%, and 92.1% of one-, two-, and three-stent eyes, respectively. Furthermore, 64.9%, 85.4%, and 92.1% of the three respective groups achieved unmedicated IOP ≤15 mmHg. Over the 18-month follow-up period, medication was required in seven one-stent subjects, four two-stent subjects, and three three-stent subjects. At 18 months, mean unmedicated IOP was 15.9±0.9 mmHg in one-stent subjects, 14.1±1.0 mmHg in two-stent subjects, and 12.2±1.1 mmHg in three-stent subjects. Month 18 IOP reduction was significantly greater (P<0.001) with implantation of each additional stent, with mean differences in reduction of 1.84 mmHg (95% confidence interval 0.96-2.73) for three-stent vs two-stent groups and 1.73 mmHg (95% confidence interval 0.83-2.64) for two-stent vs one-stent groups. Adverse events through 18 months were limited to cataract progression with best-corrected visual acuity loss and subsequent cataract surgery.
In this series, implantation of each additional stent resulted in significantly greater IOP reduction with reduced medication use. Titratability of stents as a sole procedure was shown to be effective and safe, with sustained effect through 18 months postoperatively in OAG not controlled with medication.
One of the most captivating problems being faced nowadays in Physics are ultra-high energy cosmic rays. They are high-energy radiations coming mainly from outside the Solar System, and when they ...enter Earth’s atmosphere, they produce a cascade of particles. This cascade of particles, named as extensive air shower, can be recorded by means of photomultiplier tubes in surface detectors, obtaining different recordings of the energy signal (since the air shower can hit one or more detectors). Based on these signals, different features can be obtained that might give an insight into which particle has caused the extensive air shower, which is of utmost importance for physicists. Therefore, this work presents a supervised learning algorithm to determine that the particle is a photon or a hadron. Convolutional neural networks and feed forward neural networks are compared in order to analyze the importance of spatial information for the classification. Then, a comparison between using the information of each surface detector separately and integrating the information from them for the classification is studied, showing that the integration improves the results compared to using each surface detector’s trace independently. Furthermore, a comparison between manually extracted features from the signal and the automatically extracted features by the convolutional neural network is done, showing the classification potential of the latter. Finally, the addition of particle shower features which are external to the surface detector measurements is assessed, showing that the combination of automatically extracted features and external variables is able to predict the particle that has produced the air shower with an accuracy of 98.87%.
We discuss the spectrum of the different components in the astrophysical neutrino flux reaching the Earth, and the possible contribution of each component to the high-energy IceCube data. We show ...that the diffuse flux from cosmic ray (CR) interactions with gas in our galaxy implies just two events among the 54-event sample. We argue that the neutrino flux from CR interactions in the intergalactic (intracluster) space depends critically on the transport parameter δ describing the energy dependence in the diffusion coefficient of galactic CRs. Our analysis motivates a neutrino spectrum with a drop at PeV energies that fits the data well, including the non-observation of the Glashow resonance at 6.3 PeV. We also show that a CR flux described by an unbroken power law may produce a neutrino flux with interesting spectral features (bumps and breaks) related to changes in the CR composition.
We present the first measurement of the fluctuations in the number of muons in extensive air showers produced by ultrahigh energy cosmic rays. We find that the measured fluctuations are in good ...agreement with predictions from air shower simulations. This observation provides new insights into the origin of the previously reported deficit of muons in air shower simulations and constrains models of hadronic interactions at ultrahigh energies. Our measurement is compatible with the muon deficit originating from small deviations in the predictions from hadronic interaction models of particle production that accumulate as the showers develop.
Major Depressive Disorder (MDD) entails cognitive dysfunction in many cognitive domains, but it is still uncertain whether such deficits are present in the early stages. The purpose of the study is ...to determine the cognitive performance in first episode depression (FED) exploring the presence of different cognitive profiles, and the role of cognition in FED at baseline and long-term. Ninety subjects (18–50 years) were included, 50 patients with a FED and 40 healthy controls. Participants were assessed with a neuropsychological battery, covering language, attention, verbal memory, processing speed and executive domains. Neuropsychological group comparisons were performed with MANOVAs. A hierarchical cluster analysis was run to identify clusters of patients with similar neuropsychological performance. Two generalized linear models were built to predict baseline HDRS-17 and changes at 12 months. Patients performed significantly worse than healthy controls in language, attention/working memory, verbal memory, processing speed and executive functioning, with moderate to large effect sizes (0.5 - 1). Two clusters were found: cognitively preserved patients (n=37) and cognitively impaired patients (n=13). Large effect sizes of cognitive impairment in FED were observed between the two cognitive clusters (preserved and impaired). Depressive symptoms at baseline were predicted by verbal memory (p=0.003), while 12-month changes were predicted by executive function (p=0.041) and language (p=0.037). Cognitive performance predicted depressive symptoms at baseline and at follow-up, pointing to the usefulness of cognitive assessment even at the commencement of the illness.
•White matter alterations may be underneath the pathophysiology of depression at early-stages.•Longitudinal studies of first-episode patients address long-term course of illness.•Importance of ...exploring simultaneously grey and white matter in major depressive disorders is determined.
Major depressive disorder (MDD) is accompanied by atypical brain structure affecting grey and white matter from the early stages. Neuroimaging studies of first-episode depression (FED) have provided evidence on this regard, but most of the studies are cross-sectional. The aim of this longitudinal study was to test potential changes in grey matter (GM) and white matter (WM) volumes in FED.
Thirty-three untreated FED patients (DSM-IV criteria) and 33 healthy controls (HC) underwent a 3T structural magnetic resonance imaging (sMRI) at baseline and after 2 years. Depressive symptoms were assessed at baseline and throughout the study with the 17-item Hamilton Depressive Rating Scale (HDRS-17). Recurrences of FED patients were also collected along the follow-up. To analyze GM and WM differences, whole-brain voxel-based morphometry (VBM, SPM12) was employed (FWE corrected).
FED patients showed significant reductions compared to HC in WM volumes of prefrontal cortex (left anterior corona radiata). No differences were found in GM volumes. Full factorial longitudinal analysis of the whole sample revealed no significant effect in GM nor in WM, while the full factorial longitudinal analysis comparing recurrent and non-recurrent patients showed increments in WM volumes of left posterior corona radiata and right posterior thalamic radiation in the recurrent group.
Limited sample size, especially in the follow-up.
The present findings provided some new evidence of the role of white matter alterations in the early stages of MDD and in the progression of the illness.
Abstract The habenula (Hb) can play an important role in major depressive disorder (MDD) as it is a key node between fronto-limbic areas and midbrain monoaminergic structures. In vivo neuroimaging ...studies have shown reductions in Hb volume in a post-mortem sample of patients with affective disorders but findings in unipolar MDD are not consistent. The current study aimed to investigate whether the Hb volume differed between patients with different stages of unipolar MDD and healthy subjects. We also explored differences in grey (GM) and white matter (WM) volumes and potential age and gender effects. High-resolution images were acquired using a 3T-scanner from 95 participants (21 with first-episode MDD; 20 with remitted-recurrent MDD; 20 with treatment-resistant/chronic MDD; and 34 healthy controls).Two researchers blinded to clinical data manually delineated habenular nuclei, with excellent inter-rater agreement. Multivariate analysis of covariance revealed a significant group-by-gender interaction ( F9,258 =2.22; p =0.02). Univariate effects emerged for Hb-WM volumes ( F3,86 =3.12; p =0.03) but not for total Hb volumes ( F3,86 =0.59; p =0.62) or Hb-GM volumes ( F3,86 =2.01; p =0.12). Women with a first-episode MDD had greater Hb-WM volumes than healthy controls and patients with treatment-resistant/chronic MDD ( p <0.01). These findings remained unaltered when controlled for total intracranial volume or medication load. Our results do not support decreased total Hb volumes in unipolar MDD, in patients with first-episode or in patients with long-lasting recurrent or chronic depression. However, the increased Hb-WM volume we observed in women with a first-episode suggests involvement of Hb and its projections in early stages of the recovery process and in the course of MDD.
Tropospheric ozone (O3) is an environmental pollutant of growing concern, especially in suburban and rural areas where the density of air quality monitoring stations is not high. In this type of ...areas citizen science strategies can be useful tools for awareness raising, but sensor technologies must be validated before sensor data are communicated to the public. In this work, the performance under field conditions of two custom-made types of ozone sensing devices, based on metal-oxide and electrochemical sensors, was tested. A large array of 132 metal-oxide (Sensortech MICS 2614) and 11 electrochemical (Alphasense) ozone sensors, built into 44 sensing devices, was co-located at reference stations in Italy (4 stations) and Spain (5). Mean R2 between sensor and reference data was 0.88 (0.78–0.96) and 0.89 (0.73–0.96) for Captor (metal-oxide) and Raptor (electrochemical) nodes. The metal-oxide sensors showed an upper limit (approximately 170 μg/m3) implying that these sensors may be useful to communicate mean ozone concentrations but not peak episodes. The uncertainty of the nodes was 10% between 100 and 150 μg/m3 and 20% between 150 and 200 μg/m3, for Captors, and 10% for >100 μg/m3 for Raptors. Operating both types of nodes up to 5 months did not evidence any clear influence of drifts. The use of these sensors in citizen science can be a useful tool for awareness raising. However, significant data processing efforts are required to ensure high data quality, and thus machine learning strategies are advisable. Relative uncertainties should always be reported when communicating ozone concentration data from sensing nodes.
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•Citizen science is useful for awareness raising, if sensors are validated.•Performance of 143 ozone electrochemical and metal-oxide sensors was tested.•R2 between sensor and reference data was 0.88 (0.78–0.96) and 0.89 (0.73–0.96).•Sensors tested are useful to communicate daily means but not peak episodes.•Uncertainties must always be communicated to the public.
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