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Since 2018, the Aeolus satellite of the European Space Agency (ESA) has acquired wind HLOS (horizontal line-of-sight) profiles throughout the troposphere and up to the lower stratosphere, filling a critical gap in the Global Observing System (GOS). Aeolus, carrying ALADIN (Atmospheric LAser Doppler INstrument), the first UV HSRL (High Spectral Resolution Lidar) Doppler lidar ever placed in space, provides also vertically resolved optical properties of particulates (aerosols and clouds). The present study focuses on the assessment of Aeolus L2A particulate backscatter coefficient (baseline 2A11), retrieved by the Standard Correct Algorithm (SCA), in the eastern Mediterranean, a region hosting a variety of aerosol species. Ground-based retrievals acquired by lidar instruments operating in Athens (central Greece), Thessaloniki (northern Greece) and Antikythera (southwestern Greece) serve as reference. All lidar stations provide routine measurements to the PANACEA (PANhellenic infrastructure for Atmospheric Composition and climatE chAnge) network. A set of ancillary data, including sun-photometric observations (AERONET), reanalysis products (CAMS and MERRA-2), satellite observations (MSG-SEVIRI and MODIS Aqua) and backward-trajectories modelling (FLEXPART), is utilized towards an optimum characterization of the probed atmospheric conditions under the absence of a classification scheme in Aeolus SCA profiles. First, emphasis is given on the assessment of Aeolus SCA backscatter coefficient under specific aerosol scenarios over Antikythera island. Due to the misdetection of the cross-polar component of the backscattered lidar signal, Aeolus underestimates the aerosol backscatter coefficient by up to 33 % when non-spherical mineral particles are recorded (10 July 2019). A good performance is revealed on 3 July 2019, when horizontally homogeneous loads of fine spherical particles are confined below 4 km. For other two cases (8 July 2020 and 5 August 2020), due to noise issues, the SCA performance degrades in terms of depicting the stratification of aerosol layers composed of particles of different origin. According to the statistical assessment analysis of 43 identified cases, a poor-to-moderate performance is revealed for the unfiltered (aerosols plus clouds) SCA profiles, which improves substantially when cloud-contaminated profiles are excluded from the collocated sample. This improvement is evident at both Aeolus vertical scales (regular scales have 24 bins and mid-bin scales have 23 bins), and it is justified by the drastic reduction in the bias (from 0.45 to 0.27 Mm−1 sr−1 for SCA and from 0.69 to 0.37 Mm−1 sr−1 for SCA mid-bin) and root mean square error (from 2.00 to 1.65 Mm−1 sr−1 for SCA and from 1.88 to 1.00 Mm−1 sr−1 for SCA mid-bin) scores. In the vertical, the SCA performance degrades at the lowermost bins due to either the contamination from surface signals or the increased noise levels for the aerosol retrievals. Among the three PANACEA stations, the best agreement is found at the remote site of Antikythera with respect to the urban sites of Athens and Thessaloniki. Finally, all key Cal/Val (calibration and validation) aspects necessary for future relevant studies, the recommendations for a possible Aeolus follow-on mission and an overview of the ongoing related activities are thoroughly discussed.

The eVe dual-laser/dual-telescope lidar system is introduced here, focusing on the optical and mechanical parts of the system's emission and receiver units. The compact design of the linear–circular emission unit along with the linear–circular analyser in the receiver unit allows eVe to simultaneously reproduce the operation of the ALADIN lidar on board Aeolus as well as to operate it as a traditional ground-based polarisation lidar system with linear emission. As such, the eVe lidar aims to provide (a) ground reference measurements for the validation of the Aeolus L2A aerosol products and (b) the conditions for which linear polarisation lidar systems can be considered for Aeolus L2A validation, by identifying any possible biases arising from the different polarisation state in the emission between ALADIN and these systems, and the detection of only the co-polar component of the returned signal from ALADIN for the L2A products' retrieval. In addition, a brief description is given concerning the polarisation calibration techniques that are applied in the system, as well as the developed software for the analysis of the collected signals and the retrieval of the optical products. More specifically, the system's dual configuration enables the retrieval of the optical properties of particle backscatter and extinction coefficients originating from the two different polarisation states of the emission and the linear and circular depolarisation ratios, as well as the direct calculation of the Aeolus-like backscatter coefficient, i.e. the backscatter coefficient that Aeolus would measure from the ground. Two cases, one with slightly depolarising particles and one with moderately depolarising particles, were selected from the first conducted measurements of eVe in Athens in September 2020, in order to demonstrate the system's capabilities. In the slightly depolarising scene, the Aeolus-like backscatter coefficient agrees well with the actual backscatter coefficient, which is also true when non-depolarising particles are present. The agreement however fades out for strongly depolarising scenes, where an underestimation of ∼18 % of the Aeolus like backscatter coefficient is observed when moderately depolarising particles are probed.

Dust orientation has been an ongoing investigation in recent years. Its potential proof will be a paradigm shift for dust remote sensing, invalidating the currently used simplifications of randomly oriented particles. Vertically resolved measurements of dust orientation can be acquired with a polarization lidar designed to target the off-diagonal elements of the backscatter matrix which are nonzero only when the particles are oriented. Building on previous studies, we constructed a lidar system emitting linearly and elliptically polarized light at 1064 nm and detecting the linear and circular polarization of the backscattered light. Its measurements provide direct flags of dust orientation, as well as more detailed information of the particle microphysics. The system also has the capability to acquire measurements at varying viewing angles. Moreover, in order to achieve good signal-to-noise ratio in short measurement times, the system is equipped with two laser sources emitting in an interleaved fashion and two telescopes for detecting the backscattered light from both lasers. Herein we provide a description of the optical and mechanical parts of this new lidar system, the scientific and technical objectives of its design, and the calibration methodologies tailored for the measurements of oriented dust particles. We also provide the first, preliminary measurements of the system during a dust-free day. The work presented does not include the detection of oriented dust (or other oriented particles), and therefore the instrument has not been tested fully in this objective.

Myasthenia gravis (MG) is a rare autoantibody-mediated disease affecting the neuromuscular junction. We performed a genome-wide association study of 5708 MG cases and 432,028 controls of European ancestry and a replication study in 3989 cases and 226,643 controls provided by 23andMe Inc. We identified 12 independent genome-wide significant hits (P

Tourette syndrome (TS) is a neuropsychiatric disorder of complex genetic architecture involving multiple interacting genes. Here, we sought to elucidate the pathways that underlie the neurobiology of the disorder through genome-wide analysis. We analyzed genome-wide genotypic data of 3581 individuals with TS and 7682 ancestry-matched controls and investigated associations of TS with sets of genes that are expressed in particular cell types and operate in specific neuronal and glial functions. We employed a self-contained, set-based association method (SBA) as well as a competitive gene set method (MAGMA) using individual-level genotype data to perform a comprehensive investigation of the biological background of TS. Our SBA analysis identified three significant gene sets after Bonferroni correction, implicating ligand-gated ion channel signaling, lymphocytic, and cell adhesion and transsynaptic signaling processes. MAGMA analysis further supported the involvement of the cell adhesion and trans-synaptic signaling gene set. The lymphocytic gene set was driven by variants in FLT3, raising an intriguing hypothesis for the involvement of a neuroinflammatory element in TS pathogenesis. The indications of involvement of ligand-gated ion channel signaling reinforce the role of GABA in TS, while the association of cell adhesion and trans-synaptic signaling gene set provides additional support for the role of adhesion molecules in neuropsychiatric disorders. This study reinforces previous findings but also provides new insights into the neurobiology of TS.

Lorcaserin is a serotonin 2c receptor agonist that promotes weight loss while contributing to the prevention and improvement of type 2 diabetes and improvement of atherogenic lipid profiles, without higher rates of major cardiovascular events. The full spectrum of possible lorcaserin-induced improvements in cardiometabolic health remains to be clarified. Thus, we investigated the way in which lorcaserin treatment may alter cardiovascular disease risk, either independently or through changes in body weight. We measured, for the first time, lipid particle quantification, lipid peroxidation, appetite-regulating hormones and mRNA expression of the 5-hydroxytryptamine 2c receptor (5-HT2c receptor). A total of 48 obese participants were enrolled in this six-month, randomized (1:1), placebo-controlled, double-blinded clinical trial. Lorcaserin treatment reduced fat mass (P

ObjectiveTourette's syndrome is polygenic and highly heritable. Genome-wide association study (GWAS) approaches are useful for interrogating the genetic architecture and determinants of Tourette's syndrome and other tic disorders. The authors conducted a GWAS meta-analysis and probed aggregated Tourette's syndrome polygenic risk to test whether Tourette's and related tic disorders have an underlying shared genetic etiology and whether Tourette's polygenic risk scores correlate with worst-ever tic severity and may represent a potential predictor of disease severity.MethodsGWAS meta-analysis, gene-based association, and genetic enrichment analyses were conducted in 4,819 Tourette's syndrome case subjects and 9,488 control subjects. Replication of top loci was conducted in an independent population-based sample (706 case subjects, 6,068 control subjects). Relationships between Tourette's polygenic risk scores (PRSs), other tic disorders, ascertainment, and tic severity were examined.ResultsGWAS and gene-based analyses identified one genome-wide significant locus within FLT3 on chromosome 13, rs2504235, although this association was not replicated in the population-based sample. Genetic variants spanning evolutionarily conserved regions significantly explained 92.4% of Tourette's syndrome heritability. Tourette's-associated genes were significantly preferentially expressed in dorsolateral prefrontal cortex. Tourette's PRS significantly predicted both Tourette's syndrome and tic spectrum disorders status in the population-based sample. Tourette's PRS also significantly correlated with worst-ever tic severity and was higher in case subjects with a family history of tics than in simplex case subjects.ConclusionsModulation of gene expression through noncoding variants, particularly within cortico-striatal circuits, is implicated as a fundamental mechanism in Tourette's syndrome pathogenesis. At a genetic level, tic disorders represent a continuous spectrum of disease, supporting the unification of Tourette's syndrome and other tic disorders in future diagnostic schemata. Tourette's PRSs derived from sufficiently large samples may be useful in the future for predicting conversion of transient tics to chronic tic disorders, as well as tic persistence and lifetime tic severity.

There have been considerable recent advances in understanding the genetic architecture of Tourette syndrome (TS) as well as its underlying neurocircuitry. However, the mechanisms by which genetic variation that increases risk for TS-and its main symptom dimensions-influence relevant brain regions are poorly understood. Here we undertook a genome-wide investigation of the overlap between TS genetic risk and genetic influences on the volume of specific subcortical brain structures that have been implicated in TS. We obtained summary statistics for the most recent TS genome-wide association study (GWAS) from the TS Psychiatric Genomics Consortium Working Group (4644 cases and 8695 controls) and GWAS of subcortical volumes from the ENIGMA consortium (30,717 individuals). We also undertook analyses using GWAS summary statistics of key symptom factors in TS, namely social disinhibition and symmetry behaviour. SNP effect concordance analysis (SECA) was used to examine genetic pleiotropy-the same SNP affecting two traits-and concordance-the agreement in single nucelotide polymorphism (SNP) effect directions across these two traits. In addition, a conditional false discovery rate (FDR) analysis was performed, conditioning the TS risk variants on each of the seven subcortical and the intracranial brain volume GWAS. Linkage disequilibrium score regression (LDSR) was used as validation of the SECA method. SECA revealed significant pleiotropy between TS and putamen (p = 2 × 10-4) and caudate (p = 4 × 10-4) volumes, independent of direction of effect, and significant concordance between TS and lower thalamic volume (p = 1 × 10-3). LDSR lent additional support for the association between TS and thalamus volume (p = 5.85 × 10-2). Furthermore, SECA revealed significant evidence of concordance between the social disinhibition symptom dimension and lower thalamus volume (p = 1 × 10-3), as well as concordance between symmetry behaviour and greater putamen volume (p = 7 × 10-4). Conditional FDR analysis further revealed novel variants significantly associated with TS (p