Design and Fabrication of the All-Reflecting H-Lyman alpha Coronagraph/Polarimeter

We have designed, analyzed, and are now fabricating an All-Reflecting H-Lyman alpha Coronagraph/Polarimeter for solar research. This new instrument operates in a narrow bandpass centered at lambda 1215.7 A-the neutral hydrogen Lyman alpha (Ly-alpha) line. It is shorter and faster than the telescope which produced solar Ly-alpha images as a part of the MSSTA payload that was launched on May 13, 1991. The Ly-alpha line is produced and linearly polarized in the solar corona by resonance scattering, and the presence of a magnetic field modifies this polarization according to the Hanle effect. The Lyman alpha Coronagraph/Polarimeter instrument has been designed to measure coronal magnetic fields by interpreting, via the Hanle effect, the measured linear polarization of the coronal Ly-alpha line. Ultrasmooth mirrors, polarizers, and filters are being flow-polished for this instrument from CVD silicon carbide substrates. These optical components will be coated using advanced induced transmission and absorption thin film multilayer coatings, to optimize the reflectivity and polarization properties at 1215.7 A. We describe some of the solar imaging results obtained with the MSSTA Lyman alpha coronagraph. We also discuss the optical design parameters and fabrication plans for the All-Reflecting H-Lyman alpha Coronagraph/Polarimeter

Expanded national database collection and data coverage in the FINDbase worldwide database for clinically relevant genomic variation allele frequencies

FINDbase (http://www.findbase.org) is a comprehensive data repository that records the prevalence of clinically relevant genomic variants in various populations worldwide, such as pathogenic variants leading mostly to monogenic disorders and pharmacogenomics biomarkers. The database also records the incidence of rare genetic diseases in various populations, all in well-distinct data modules. Here, we report extensive data content updates in all data modules, with direct implications to clinical pharmacogenomics. Also, we report significant new developments in FINDbase, namely (i) the release of a new version of the ETHNOS software that catalyzes development curation of national/ethnic genetic databases, (ii) the migration of all FINDbase data content into 90 distinct national/ethnic mutation databases, all built around Microsoft’s PivotViewer (http://www.getpivot.com) software (iii) new data visualization tools and (iv) the interrelation of FINDbase with DruGeVar database with direct implications in clinical pharmacogenomics. The above mentioned updates further enhance the impact of FINDbase, as a key resource for Genomic Medicine applications

Behavioral and Neuroimaging Research on Developmental Coordination Disorder (DCD): A Combined Systematic Review and Meta-Analysis of Recent Findings

Data Availability Statement: The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s. Supplementary Material: The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpsyg.2022.809455/full#supplementary-materialAim: The neurocognitive basis of Developmental Coordination Disorder (DCD; or motor clumsiness) remains an issue of continued debate. This combined systematic review and meta-analysis provides a synthesis of recent experimental studies on the motor control, cognitive, and neural underpinnings of DCD. Methods: The review included all published work conducted since September 2016 and up to April 2021. One-hundred papers with a DCD-Control comparison were included, with 1,374 effect sizes entered into a multi-level meta-analysis. Results: The most profound deficits were shown in: voluntary gaze control during movement; cognitive-motor integration; practice-/context-dependent motor learning; internal modeling; more variable movement kinematics/kinetics; larger safety margins when locomoting, and atypical neural structure and function across sensori-motor and prefrontal regions. Interpretation: Taken together, these results on DCD suggest fundamental deficits in visual-motor mapping and cognitive-motor integration, and abnormal maturation of motor networks, but also areas of pragmatic compensation for motor control deficits. Implications for current theory, future research, and evidence-based practice are discussed. Systematic Review Registration: PROSPERO, identifier: CRD42020185444.Australian Government Research Training Program Scholarship; Research Centre scheme, Australian Catholic University; Czech Science Foundation (GACR EXPRO scheme: 21-15728X); Knut and Alice Wallenberg Foundation (KAW 2020.0200).https://www.frontiersin.org/articles/10.3389/fpsyg.2022.809455/full#supplementary-materia

A far ultraviolet imager for the International Solar-Terrestrial Physics Mission

The aurorae are the result of collisions with the atmosphere of energetic particles that have their origin in the solar wind, and reach the atmosphere after having undergone varying degrees of acceleration and redistribution within the Earth's magnetosphere. The global scale phenomenon represented by the aurorae therefore contains considerable information concerning the solar-terrestrial connection. For example, by correctly measuring specific auroral emissions, and with the aid of comprehensive models of the region, we can infer the total energy flux entering the atmosphere and the average energy of the particles causing these emissions. Furthermore, from these auroral emissions we can determine the ionospheric conductances that are part of the closing of the magnetospheric currents through the ionosphere, and from these we can in turn obtain the electric potentials and convective patterns that are an essential element to our understanding of the global magnetosphere-ionosphere-thermosphere-mesosphere. Simultaneously acquired images of the auroral oval and polar cap not only yield the temporal and spatial morphology from which we can infer activity indices, but in conjunction with simultaneous measurements made on spacecraft at other locations within the magnetosphere, allow us to map the various parts of the oval back to their source regions in the magnetosphere. This paper describes the Ultraviolet Imager for the Global Geospace Sciences portion of the International Solar-Terrestrial Physics program. The instrument operates in the far ultraviolet (FUV) and is capable of imaging the auroral oval regardless of whether it is sunlit or in darkness. The instrument has an 8° circular field of view and is located on a despun platform which permits simultaneous imaging of the entire oval for at least 9 hours of every 18 hour orbit. The three mirror, unobscured aperture, optical system ( f /2.9) provides excellent imaging over this full field of view, yielding a per pixel angular resolution of 0.6 milliradians. Its FUV filters have been designed to allow accurate spectral separation of the features of interest, thus allowing quantitative interpretation of the images to provide the parameters mentioned above. The system has been designed to provide ten orders of magnitude blocking against longer wavelength (primarily visible) scattered sunlight, thus allowing the first imaging of key, spectrally resolved, FUV diagnostic features in the fully sunlit midday aurorae. The intensified-CCD detector has a nominal frame rate of 37 s, and the fast optical system has a noise equivalent signal within one frame of ∼ 10 R . The instantaneous dynamic range is >1000 and can be positioned within an overall gain range of 10 4 , allowing measurement of both the very weak polar cap emissions and the very bright aurora. The optical surfaces have been designed to be sufficiently smooth to permit this dynamic range to be utilized without the scattering of light from bright features into the weaker features. Finally, the data product can only be as good as the degree to which the instrument performance is characterized and calibrated. In the VUV, calibration of an an imager intended for quantitative studies is a task requiring some pioneering methods, but it is now possible to calibrate such an instrument over its focal plane to an accuracy of ±10%. In summary, very recent advances in optical, filter and detector technology have been exploited to produce an auroral imager to meet the ISTP objectives.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43777/1/11214_2004_Article_BF00751335.pd

A European spectrum of pharmacogenomic biomarkers: Implications for clinical pharmacogenomics

Pharmacogenomics aims to correlate inter-individual differences of drug efficacy and/or toxicity with the underlying genetic composition, particularly in genes encoding for protein factors and enzymes involved in drug metabolism and transport. In several European populations, particularly in countries with lower income, information related to the prevalence of pharmacogenomic biomarkers is incomplete or lacking. Here, we have implemented the microattribution approach to assess the pharmacogenomic biomarkers allelic spectrum in 18 European populations, mostly from developing European countries, by analyzing 1,931 pharmacogenomics biomarkers in 231 genes. Our data show significant interpopulation pharmacogenomic biomarker allele frequency differences, particularly in 7 clinically actionable pharmacogenomic biomarkers in 7 European populations, affecting drug efficacy and/or toxicity of 51 medication treatment modalities. These data also reflect on the differences observed in the prevalence of high-risk genotypes in these populations, as far as common markers in the CYP2C9, CYP2C19, CYP3A5, VKORC1, SLCO1B1 and TPMT pharmacogenes are concerned. Also, our data demonstrate notable differences in predicted genotype-based warfarin dosing among these populations. Our findings can be exploited not only to develop guidelines for medical prioritization, but most importantly to facilitate integration of pharmacogenomics and to support pre-emptive pharmacogenomic testing. This may subsequently contribute towards significant cost-savings in the overall healthcare expenditure in the participating countries, where pharmacogenomics implementation proves to be cost-effective

Clinical application of thiopurine pharmacogenomics in pediatrics

Background: Thiopurine drugs are used for the treatment of pediatric diseases. Inter-individual differences in the metabolism of these drugs greatly influence the risk of thiopurine induced toxicity and therapy failure. These differences are the consequence of genomic, epigenomic and transcriptomic variability among patients. Phar-macogenomics aims to individualize therapy according to the specific genetic signature of a patient. Treatment pro-tocols based on thiopurine drugs have already been improved by applying pharmacogenomics in pediatric clinical practice. Objective: The aim of this review was to summarize the application of thiopurine pharmacogenomics in pediatric patients suffering from acute leukemias, different types of autoimmune and inflammatory diseases, as well as in post-transplant care. Methods: We searched PubMed/Medline database to identify thiopurine pharmacogenomic markers clinically relevant in pediatric diseases. Results: TPMT and NUDT15 pharmacogenomic testing is done in pediatric care, contributing to the reduction of thiopurine induced toxicity. Data on numerous novel potential pharmacogenomic markers relevant for optimization of thiopurine treatment are still controversial (ITPA, ABCC4, NT5C2, PRPS1, GSTM1, FTO gene variants). Majority of evidences regarding thiopurine pharmacogenomics in pediatrics have been acquired by studying acute lym-phoblastic leukemia and inflammatory bowel disease. For other pediatric diseases, namely acute myeloid leukemia, non-Hodgkin lymphoma, juvenile idiopathic arthritis, atopic dermatitis, juvenile autoimmune hepatitis and renal allograft transplantation, data are still scarce. Conclusion: Thiopurine pharmacogenomics has shown to be one of the best examples of successful application of pharmacogenomics in pediatrics

Epigenetic signature of early trauma: differences in the FKBP5 DNA methylation levels among psychotic patients, their healthy siblings and controls

30th Congress of the European-College-of-Neuropsychopharmacology (ECNP), Sep 02-05, 2017, Paris, Franc

Epigenetic signature of early trauma: differences in the FKBP5 DNA methylation levels among psychotic patients, their healthy siblings and controls

30th Congress of the European-College-of-Neuropsychopharmacology (ECNP), Sep 02-05, 2017, Paris, Franc

Data_Sheet_1_Locomotor-cognitive dual-tasking in children with developmental coordination disorder.docx

IntroductionChildren with Developmental Coordination Disorder (DCD) demonstrate deficits in predictive motor control and aspects of cognitive control compared with their typically developing (TD) peers. Adjustment to dynamic environments depends on both aspects of control and the deficits for children with DCD may constrain their ability to perform daily actions that involve dual-tasking. Under the assumption that motor-cognitive integration is compromised in children with DCD, we examined proportional dual-task costs using a novel locomotor-cognitive dual-task paradigm that enlisted augmented reality. We expect proportional dual-task performance costs to be greater for children with DCD compared to their TD peers.MethodsParticipants were 34 children aged 6–12 years (16 TD, 18 DCD) who walked along a straight 12 m path under single- and dual-task conditions, the cognitive task being visual discrimination under simple or complex stimulus conditions presented via augmented reality. Dual-task performance was measured in two ways: first, proportional dual-task costs (pDTC) were computed for cognitive and gait outcomes and, second, within-trial costs (p-WTC) were measured as the difference on gait outcomes between pre- and post-stimulus presentation.ResultsOn measures of pDTC, TD children increased their double-limb support time when walking in response to a dual-task, while the children with DCD increased their locomotor velocity. On p-WTC, both groups increased their gait variability (step length and step width) when walking in response to a dual-task, of which the TD group had a larger proportional change than the DCD group. Greater pDTCs on motor rather than cognitive outcomes were consistent across groups and method of dual-task performance measurement.DiscussionContrary to predictions, our results failed to support dramatic differences in locomotor-cognitive dual-task performance between children with DCD and TD, with both groups tending to priorities the cognitive over the motor task. Inclusion of a within-trial calculation of dual-task interference revealed an expectancy effect for both groups in relation to an impending visual stimulus. It is recommended that dual-task paradigms in the future continue to use augmented reality to present the cognitive task and consider motor tasks of sufficient complexity to probe the limits of performance in children with DCD.</p