Search

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience. The authors pooled resources to identify best practices and develop a new standardized protocol for estimating functional connectivity in rats with magnetic resonance imaging.

Weitere Nicht-UDE Autoren sind nicht mit aufgeführt. in press

Appendix D. Additional thin section microphotographs of HD1 sample showing repeated cycles of syntaxial grain growth.

Appendix A: 3D Virtual Outcrop Models and analytical methodologies; Appendix B: Regional stratigraphy; Appendix C: Detrital heavy mineral data.

OBJECTIVE: To determine the incremental yield of exome sequencing (ES) over chromosomal microarray analysis (CMA) or karyotyping in prenatally diagnosed non-immune hydrops fetalis (NIHF). METHODS: A prospective cohort study (comprising an extended group of the Prenatal Assessment of Genomes and Exomes (PAGE) study) was performed which included 28 cases of prenatally diagnosed NIHF undergoing trio ES following negative CMA or karyotyping. These cases were combined with data from a systematic review of the literature. MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov databases were searched electronically (January 2000 to October 2020) for studies reporting on the incremental yield of ES over CMA or karyotyping in fetuses with prenatally detected NIHF. Inclusion criteria for the systematic review were: (i) at least two cases of NIHF undergoing sequencing; (ii) testing initiated based on prenatal ultrasound-based phenotype; and (iii) negative CMA or karyotyping result. The incremental diagnostic yield of ES was assessed in: (i) all cases of NIHF; (ii) isolated NIHF; (iii) NIHF associated with an additional fetal structural anomaly; and (iv) NIHF according to severity (i.e. two vs three or more cavities affected). RESULTS: In the extended PAGE study cohort, the additional diagnostic yield of ES over CMA or karyotyping was 25.0% (7/28) in all NIHF cases, 21.4% (3/14) in those with isolated NIHF and 28.6% (4/14) in those with non-isolated NIHF. In the meta-analysis, the pooled incremental yield based on 21 studies (306 cases) was 29% (95% CI, 24-34%; P < 0.00001; I2 = 0%) in all NIHF, 21% (95% CI, 13-30%; P < 0.00001; I2 = 0%) in isolated NIHF and 39% (95% CI, 30-49%; P < 0.00001; I2 = 1%) in NIHF associated with an additional fetal structural anomaly. In the latter group, congenital limb contractures were the most prevalent additional structural anomaly associated with a causative pathogenic variant, occurring in 17.3% (19/110) of cases. The incremental yield did not differ significantly according to hydrops severity. The most common genetic disorders identified were RASopathies, occurring in 30.3% (27/89) of cases with a causative pathogenic variant, most frequently due to a PTPN11 variant (44.4%; 12/27). The predominant inheritance pattern in causative pathogenic variants was autosomal dominant in monoallelic disease genes (57.3%; 51/89), with most being de novo (86.3%; 44/51). CONCLUSIONS: Use of prenatal next-generation sequencing in both isolated and non-isolated NIHF should be considered in the development of clinical pathways. Given the wide range of potential syndromic diagnoses and heterogeneity in the prenatal phenotype of NIHF, exome or whole-genome sequencing may prove to be a more appropriate testing approach than a targeted gene panel testing strategy. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

We perform phantom and numerical studies of the changes in molecular oxygen and water vapor spectroscopic signals, showing the potential of measuring pulmonary volume changes with GASMAS technique in neonates.

Background Data monitoring of clinical trials is a tool aimed at reducing the risks of random errors (e.g. clerical errors) and systematic errors, which include misinterpretation, misunderstandings, and fabrication. Traditional ‘good clinical practice data monitoring’ with on-site monitors increases trial costs and is time consuming for the local investigators. This paper aims to outline our approach of time-effective central data monitoring for the SafeBoosC-III multicentre randomised clinical trial and present the results from the first three central data monitoring meetings. Methods The present approach to central data monitoring was implemented for the SafeBoosC-III trial, a large, pragmatic, multicentre, randomised clinical trial evaluating the benefits and harms of treatment based on cerebral oxygenation monitoring in preterm infants during the first days of life versus monitoring and treatment as usual. We aimed to optimise completeness and quality and to minimise deviations, thereby limiting random and systematic errors. We designed an automated report which was blinded to group allocation, to ease the work of data monitoring. The central data monitoring group first reviewed the data using summary plots only, and thereafter included the results of the multivariate Mahalanobis distance of each centre from the common mean. The decisions of the group were manually added to the reports for dissemination, information, correcting errors, preventing furture errors and documentation. Results The first three central monitoring meetings identified 156 entries of interest, decided upon contacting the local investigators for 146 of these, which resulted in correction of 53 entries. Multiple systematic errors and protocol violations were identified, one of these included 103/818 randomised participants. Accordingly, the electronic participant record form (ePRF) was improved to reduce ambiguity. Discussion We present a methodology for central data monitoring to optimise quality control and quality development. The initial results included identification of random errors in data entries leading to correction of the ePRF, systematic protocol violations, and potential protocol adherence issues. Central data monitoring may optimise concurrent data completeness and may help timely detection of data deviations due to misunderstandings or fabricated data.

We report the deep distributions of noble gases, helium isotopes, and radiocarbon measured during the U.S. GEOTRACES GP16 East Pacific Zonal Transect between 152 and 77°W at 12–15°S in the South Pacific. The dominant feature is an intense tongue of hydrothermal effluent that extends > 4000 km westward from the East Pacific Rise (EPR) at ~ 2500 m depth. The patterns reveal significant “downstream” variations in water mass structure, advection, and mixing that belie the simple perception of a continuous plume extending westward from the EPR. For example, one feature observed at 120°W, 14°S has tracer signatures that are consistent with a water mass originating from an area as much as 2000 km south of this section, suggesting a quasi-permanent northward flow on the western flank of the EPR. Helium isotope variations in the plume show a uniquely high 3 He/ 4 He source in the tongue compared with typical mid-ocean ridge basalts (MORB), consistent with the anomalously high ratios observed in MORB glasses from the EPR segment just south of this transect. The water column data also reveal that the background 3 He/ 4 He east of the EPR is significantly lower than values characteristic of MORB, suggesting an additional, more geographically distributed radiogenic 4 He flux of order 10 7 mol/y into the deep Pacific. In the western end of the section, incoming bottom waters have relatively less hydrothermal hydrothermal helium, more radiocarbon, and more oxygen, as well as negative saturation anomalies for the heavy noble gases (Ar, Kr, and Xe). During the basin-scale upwelling of this water, diapycnal mixing serves to erase these negative anomalies. The relative magnitudes of the increases for the heavy noble gases (Ar, Kr, and Xe) are quantitatively consistent with this process. This leads us to estimate the relatively smaller effects on He and Ne saturations, which range from near zero to 0.2% and 0.3% respectively. With this information, we are able to refine our estimates of the magnitude of 3 He and 4 He excesses and the absolute 3 He/ 4 He ratio of non-atmospheric helium introduced into deep Pacific waters.

Contains fulltext : 196096.pdf (Publisher’s version ) (Open Access) Advances in neonatal cardiac imaging permit a more comprehensive assessment of myocardial performance in neonates that could not be previously obtained with conventional imaging. Myocardial deformation analysis is an emerging quantitative echocardiographic technique to characterize global and regional ventricular function in neonates. Cardiac strain is a measure of tissue deformation and strain rate is the rate at which deformation occurs. These measurements are obtained in neonates using tissue Doppler imaging (TDI) or two-dimensional speckle tracking echocardiography (STE). There is an expanding body of literature describing longitudinal reference ranges and maturational patterns of strain values in term and preterm infants. A thorough understanding of deformation principles, the technical aspects, and clinical applicability is a prerequisite for its routine clinical use in neonates. This review explains the fundamental concepts of deformation imaging in the term and preterm population, describes in a comparative manner the two major deformation imaging methods, provides a practical guide to the acquisition and interpretation of data, and discusses their recognized and developing clinical applications in neonates.

We observed large water column anomalies in helium isotopes and trace metal concentrations above the Loihi Seamount. The 3He/4He of the added helium was 27.3 times the atmospheric ratio, clearly marking its origin to a primitive mantle plume. The dissolved iron to 3He ratio (dFe:3He) exported to surrounding waters was 9.3 ± 0.3 × 10 6 . We observed the Loihi 3He and dFe “signal” at a depth of 1100 m at several stations within ∼100 – 1000 km of Loihi, which exhibited a distal dFe:3He ratio of ∼ 4 × 10 6 , about half the proximal ratio. These ratios were remarkably similar to those observed over and near the Southern East Pacific Rise (SEPR) despite greatly contrasting geochemical and volcanic-tectonic origins. In contrast, the proximal and distal dMn:3He ratios were both ∼ 1 × 10 6 , less than half of that observed at the SEPR. Dissolved methane was minimally enriched in waters above Loihi Seamount and was distally absent. Using an idealized regional-scale model we replicated the historically observed regional 3He distribution, requiring a hydrothermal 3He source from Loihi of 10.4 ± 4.2 mol a−1, ∼2% of the global abyssal hydrothermal 3He flux. From this we compute a corresponding dFe flux of ∼40 Mmol a−1. Global circulation model simulations suggest that the Loihi-influenced waters eventually upwell along the west coast of North America, also extending into the shallow northwest Pacific, making it a possibly important determinant of marine primary production in the subpolar North Pacific.

Significant rates of primary production occur in the oligotrophic ocean, without any measurable nutrients present in the mixed layer, fueling a scientific paradox that has lasted for decades. Here, we provide a new determination of the annual mean physical supply of nitrate to the euphotic zone in the western subtropical North Atlantic. We combine a 3-year time series of measurements of tritiugenic 3He from 2003 to 2006 in the surface ocean at the Bermuda Atlantic Time-series Study (BATS) site with a sophisticated noble gas calibrated air–sea gas exchange model to constrain the 3He flux across the sea–air interface, which must closely mirror the upward 3He flux into the euphotic zone. The product of the 3He flux and the observed subsurface nitrate–3He relationship provides an estimate of the minimum rate of new production in the BATS region. We also apply the gas model to an earlier time series of 3He measurements at BATS in order to recalculate new production fluxes for the 1985 to 1988 time period. The observations, despite an almost 3-fold difference in the nitrate–3He relationship, yield a roughly consistent estimate of nitrate flux. In particular, the nitrate flux from 2003 to 2006 is estimated to be 0.65 ± 0.14 mol m−2 yr−1, which is ~40 % smaller than the calculated flux for the period from 1985 to 1988. The difference in nitrate flux between the time periods may be signifying a real difference in new production resulting from changes in subtropical mode water formation. Overall, the nitrate flux is larger than most estimates of export fluxes or net community production fluxes made locally for the BATS site, which is likely a reflection of the larger spatial scale covered by the 3He technique and potentially also by the decoupling of 3He and nitrate during the obduction of water masses from the main thermocline into the upper ocean. The upward nitrate flux is certainly large enough to support observed rates of primary production at BATS and more generally in the oligotrophic subtropical ocean.

We present the distributions of helium isotopes (in the form of helium isotope ratio anomaly relative to the atmospheric ratio) and tritium along two sections occupied in the subtropical North Atlantic as part of the first U.S. GEOTRACES survey (GEOTRACES GA03). The general distributions of these isotopes are consistent with the continuing penetration and evolution of bomb-produced tritium and its daughter isotope 3He in the main thermocline and along the western boundary current system. We combine these two distributions to compute a tritium–3He age, which is related to the elapsed time since the water was at the ocean surface. Although it is an indicator biased by the effects of mixing and influenced by the time history and spatial distribution of bomb tritium delivery to the ocean surface, it still remains a useful measure of ventilation time-scales. Aside from the continued propagation of the tritium–3He transient into the ocean interior, there are three notable features of interest in these distributions. The first is the clear signature of upwelling in the water column near the coast of Mauritania, characterized by the upward bowing of isochrones in the thermocline and discernable 3He excess at the ocean surface. A simple 3He mass balance calculation suggests an upwelling flux of order 1.8×106 m3 s−1 (1.8 Sv) along the Mauritanian coast. The second is a mid-depth (~1500–2000 m) core of ventilated waters centered over the Mid-Atlantic Ridge, an anticyclonic circulation of waters likely originating in the Labrador Sea. The third notable feature is a volcanic 3He plume at about 3500 m depth emanating from the TAG Hydrothermal Area that is detectable as much as 500 km away on each side of the Mid-Atlantic Ridge. We estimate a 3He:heat ratio of ~7×10–18 mol J−1 and a 3He flux from the TAG site of ~15 mmol y−1. Since 3He is a conserved tracer in the absence of measureable tritium, the correlation of volcanic 3He with other hydrothermally influenced TEIs (e.g., Fe) can be used as a dilution tracer as probe of non-conservative behavior in the water column. Also, since the regional and global fluxes of volcanic 3He are known, the correlations can be used as a regional/global flux gauge for hydrothermal input of those TEIs.