Genetic influences on gene expression in the human fetal brain plausibly impact upon a variety of postnatal brain-related traits, including susceptibility to neuropsychiatric disorders. However, to ...date, there have been no studies that have mapped genome-wide expression quantitative trait loci (eQTL) specifically in the human prenatal brain.
We performed deep RNA sequencing and genome-wide genotyping on a unique collection of 120 human brains from the second trimester of gestation to provide the first eQTL dataset derived exclusively from the human fetal brain. We identify high confidence cis-acting eQTL at the individual transcript as well as whole gene level, including many mapping to a common inversion polymorphism on chromosome 17q21. Fetal brain eQTL are enriched among risk variants for postnatal conditions including attention deficit hyperactivity disorder, schizophrenia, and bipolar disorder. We further identify changes in gene expression within the prenatal brain that potentially mediate risk for neuropsychiatric traits, including increased expression of C4A in association with genetic risk for schizophrenia, increased expression of LRRC57 in association with genetic risk for bipolar disorder, and altered expression of multiple genes within the chromosome 17q21 inversion in association with variants influencing the personality trait of neuroticism.
We have mapped eQTL operating in the human fetal brain, providing evidence that these confer risk to certain neuropsychiatric disorders, and identifying gene expression changes that potentially mediate susceptibility to these conditions.
Recombinant adenoviruses are among the most promising tools for vaccine antigen delivery. Recently, the development of new vectors has focused on serotypes to which the human population is less ...exposed in order to circumvent pre-existing anti vector immunity. This study describes the derivation of a new vaccine vector based on a chimpanzee adenovirus, Y25, together with a comparative assessment of its potential to elicit transgene product specific immune responses in mice. The vector was constructed in a bacterial artificial chromosome to facilitate genetic manipulation of genomic clones. In order to conduct a fair head-to-head immunological comparison of multiple adenoviral vectors, we optimised a method for accurate determination of infectious titre, since this parameter exhibits profound natural variability and can confound immunogenicity studies when doses are based on viral particle estimation. Cellular immunogenicity of recombinant E1 E3-deleted vector ChAdY25 was comparable to that of other species E derived chimpanzee adenovirus vectors including ChAd63, the first simian adenovirus vector to enter clinical trials in humans. Furthermore, the prevalence of virus neutralizing antibodies (titre >1:200) against ChAdY25 in serum samples collected from two human populations in the UK and Gambia was particularly low compared to published data for other chimpanzee adenoviruses. These findings support the continued development of new chimpanzee adenovirus vectors, including ChAdY25, for clinical use.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Coronary calcification hinders stent delivery and expansion and is associated with adverse outcomes. Intravascular lithotripsy (IVL) delivers acoustic pressure waves to modify calcium, enhancing ...vessel compliance and optimizing stent deployment.
The purpose of this study was to assess the safety and effectiveness of IVL in severely calcified de novo coronary lesions.
Disrupt CAD III (NCT03595176) was a prospective, single-arm multicenter study designed for regulatory approval of coronary IVL. The primary safety endpoint was freedom from major adverse cardiovascular events (cardiac death, myocardial infarction, or target vessel revascularization) at 30 days. The primary effectiveness endpoint was procedural success. Both endpoints were compared with a pre-specified performance goal (PG). The mechanism of calcium modification was assessed in an optical coherence tomography (OCT) substudy.
Patients (n = 431) were enrolled at 47 sites in 4 countries. The primary safety endpoint of the 30-day freedom from major adverse cardiovascular events was 92.2%; the lower bound of the 95% confidence interval was 89.9%, which exceeded the PG of 84.4% (p < 0.0001). The primary effectiveness endpoint of procedural success was 92.4%; the lower bound of the 95% confidence interval was 90.2%, which exceeded the PG of 83.4% (p < 0.0001). Mean calcified segment length was 47.9 ± 18.8 mm, calcium angle was 292.5 ± 76.5°, and calcium thickness was 0.96 ± 0.25 mm at the site of maximum calcification. OCT demonstrated multiplane and longitudinal calcium fractures after IVL in 67.4% of lesions. Minimum stent area was 6.5 ± 2.1 mm2 and was similar regardless of demonstrable fractures on OCT.
Coronary IVL safely and effectively facilitated stent implantation in severely calcified lesions.
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Optically Pumped Magnetometers (OPMs) have emerged as a viable and wearable alternative to cryogenic, superconducting MEG systems. This new generation of sensors has the advantage of not requiring ...cryogenic cooling and as a result can be flexibly placed on any part of the body. The purpose of this review is to provide a neuroscience audience with the theoretical background needed to understand the physical basis for the signal observed by OPMs. Those already familiar with the physics of MRI and NMR should note that OPMs share much of the same theory as the operation of OPMs rely on magnetic resonance. This review establishes the physical basis for the signal equation for OPMs. We re-derive the equations defining the bounds on OPM performance and highlight the important trade-offs between quantities such as bandwidth, sensor size and sensitivity. These equations lead to a direct upper bound on the gain change due to cross-talk for a multi-channel OPM system.
•We review the theoretical basis of OPMs.•We re-derive the signal equations for OPMs.•We highlight the important trade-offs in sensor design.•We discuss the practical implementation of this technology.
Optically-pumped magnetometers (OPMs) are an established alternative to superconducting sensors for magnetoencephalography (MEG), offering significant advantages including flexibility to accommodate ...any head size, uniform coverage, free movement during scanning, better data quality and lower cost. However, OPM sensor technology remains under development; there is flexibility regarding OPM design and it is not yet clear which variant will prove most effective for MEG. Most OPM-MEG implementations have either used single-axis (equivalent to conventional MEG) or dual-axis magnetic field measurements. Here we demonstrate use of a triaxial OPM formulation, able to characterise the full 3D neuromagnetic field vector. We show that this novel sensor is able to characterise magnetic fields with high accuracy and sensitivity that matches conventional (dual-axis) OPMs. We show practicality via measurement of biomagnetic fields from both the heart and the brain. Using simulations, we demonstrate how triaxial measurement offers improved cortical coverage, especially in infants. Finally, we introduce a new 3D-printed child-friendly OPM-helmet and demonstrate feasibility of triaxial measurement in a five-year-old. In sum, the data presented demonstrate that triaxial OPMs offer a significant improvement over dual-axis variants and are likely to become the sensor of choice for future MEG systems, particularly for deployment in paediatric populations.
Urbanization is a global process contributing to the loss and fragmentation of natural habitats. Many studies have focused on the biological response of terrestrial taxa and habitats to urbanization. ...However, little is known regarding the consequences of urbanization on freshwater habitats, especially small lentic systems. In this study, we examined aquatic macro‐invertebrate diversity (family and species level) and variation in community composition between 240 urban and 782 nonurban ponds distributed across the United Kingdom. Contrary to predictions, urban ponds supported similar numbers of invertebrate species and families compared to nonurban ponds. Similar gamma diversity was found between the two groups at both family and species taxonomic levels. The biological communities of urban ponds were markedly different to those of nonurban ponds, and the variability in urban pond community composition was greater than that in nonurban ponds, contrary to previous work showing homogenization of communities in urban areas. Positive spatial autocorrelation was recorded for urban and nonurban ponds at 0–50 km (distance between pond study sites) and negative spatial autocorrelation was observed at 100–150 km and was stronger in urban ponds in both cases. Ponds do not follow the same ecological patterns as terrestrial and lotic habitats (reduced taxonomic richness) in urban environments; in contrast, they support high taxonomic richness and contribute significantly to regional faunal diversity. Individual cities are complex structural mosaics which evolve over long periods of time and are managed in diverse ways. This facilitates the development of a wide range of environmental conditions and habitat niches in urban ponds which can promote greater heterogeneity between pond communities at larger scales. Ponds provide an opportunity for managers and environmental regulators to conserve and enhance freshwater biodiversity in urbanized landscapes whilst also facilitating key ecosystem services including storm water storage and water treatment.
Magnetoencephalography (MEG) is a powerful technique for functional neuroimaging, offering a non-invasive window on brain electrophysiology. MEG systems have traditionally been based on cryogenic ...sensors which detect the small extracranial magnetic fields generated by synchronised current in neuronal assemblies, however, such systems have fundamental limitations. In recent years, non-cryogenic quantum-enabled sensors, called optically-pumped magnetometers (OPMs), in combination with novel techniques for accurate background magnetic field control, have promised to lift those restrictions offering an adaptable, motion-robust MEG system, with improved data quality, at reduced cost. However, OPM-MEG remains a nascent technology, and whilst viable systems exist, most employ small numbers of sensors sited above targeted brain regions. Here, building on previous work, we construct a wearable OPM-MEG system with ‘whole-head’ coverage based upon commercially available OPMs, and test its capabilities to measure alpha, beta and gamma oscillations. We design two methods for OPM mounting; a flexible (EEG-like) cap and rigid (additively-manufactured) helmet. Whilst both designs allow for high quality data to be collected, we argue that the rigid helmet offers a more robust option with significant advantages for reconstruction of field data into 3D images of changes in neuronal current. Using repeat measurements in two participants, we show signal detection for our device to be highly robust. Moreover, via application of source-space modelling, we show that, despite having 5 times fewer sensors, our system exhibits comparable performance to an established cryogenic MEG device. While significant challenges still remain, these developments provide further evidence that OPM-MEG is likely to facilitate a step change for functional neuroimaging.
•A 49-channel whole-head OPM-MEG system is constructed.•System evaluated via repeat measurements of alpha, beta and gamma oscillations.•Two OPM-helmet designs are contrasted, a flexible (EEG-like) cap and a rigid helmet.•The rigid helmet offers significant advantages for a viable OPM-MEG device.•49-channel OPM-MEG offers performance comparable to established cryogenic devices.
•Optically pumped magnetometers can measure magnetic field vectors.•Triaxial measurements provide extra information for magnetic source imaging.•A theoretical analysis shows how triaxial measurement ...can optimise spatial filtering.•A triaxial array offers dramatic reduction in external interference and motion artefact.•Theoretical results are backed up by an experimental MEG recording.
The optically pumped magnetometer (OPM) is a viable means to detect magnetic fields generated by human brain activity. Compared to conventional detectors (superconducting quantum interference devices) OPMs are small, lightweight, flexible, and operate without cryogenics. This has led to a step change in instrumentation for magnetoencephalography (MEG), enabling a “wearable” scanner platform, adaptable to fit any head size, able to acquire data whilst subjects move, and offering improved data quality. Although many studies have shown the efficacy of ‘OPM-MEG’, one relatively untapped advantage relates to improved array design. Specifically, OPMs enable the simultaneous measurement of magnetic field components along multiple axes (distinct from a single radial orientation, as used in most conventional MEG systems). This enables characterisation of the magnetic field vector at all sensors, affording extra information which has the potential to improve source reconstruction. Here, we conduct a theoretical analysis of the critical parameters that should be optimised for effective source reconstruction. We show that these parameters can be optimised by judicious array design incorporating triaxial MEG measurements. Using simulations, we demonstrate how a triaxial array offers a dramatic improvement on our ability to differentiate real brain activity from sources of magnetic interference (external to the brain). Further, a triaxial system is shown to offer a marked improvement in the elimination of artefact caused by head movement. Theoretical results are supplemented by an experimental recording demonstrating improved interference reduction. These findings offer new insights into how future OPM-MEG arrays can be designed with improved performance.
•OPMs offer a step change for MEG, but rely on controlled magnetic field environments.•Here, optical tracking is combined with magnetometer data to create precision field maps.•Field maps are used to ...inform optimal currents in magnetic field cancellation coils.•The remnant static magnetic field experienced by the OPMs is reduced to 0.29 nT.•Motion artefact in OPM-MEG data is reduced by a factor of 5 via field nulling.
Optically-pumped magnetometers (OPMs) are highly sensitive, compact magnetic field sensors, which offer a viable alternative to cryogenic sensors (superconducting quantum interference devices – SQUIDs) for magnetoencephalography (MEG). With the promise of a wearable system that offers lifespan compliance, enables movement during scanning, and provides higher quality data, OPMs could drive a step change in MEG instrumentation. However, this potential can only be realised if background magnetic fields are appropriately controlled, via a combination of optimised passive magnetic screening (i.e. enclosing the system in layers of high-permeability materials), and electromagnetic coils to further null the remnant magnetic field. In this work, we show that even in an OPM-optimised passive shield with extremely low (<2 nT) remnant magnetic field, head movement generates significant artefacts in MEG data that manifest as low-frequency interference. To counter this effect we introduce a magnetic field mapping technique, in which the participant moves their head to sample the background magnetic field using a wearable sensor array; resulting data are compared to a model to derive coefficients representing three uniform magnetic field components and five magnetic field gradient components inside the passive shield. We show that this technique accurately reconstructs the magnitude of known magnetic fields. Moreover, by feeding the obtained coefficients into a bi-planar electromagnetic coil system, we were able to reduce the uniform magnetic field experienced by the array from a magnitude of 1.3±0.3 nT to 0.29±0.07 nT. Most importantly, we show that this field compensation generates a five-fold reduction in motion artefact at 0‒2 Hz, in a visual steady-state evoked response experiment using 6 Hz stimulation. We suggest that this technique could be used in future OPM-MEG experiments to improve the quality of data, especially in paradigms seeking to measure low-frequency oscillations, or in experiments where head movement is encouraged.
Optically-pumped magnetometers (OPMs) offer the potential for a step change in magnetoencephalography (MEG) enabling wearable systems that provide improved data quality, accommodate any subject ...group, allow data capture during movement and potentially reduce cost. However, OPM-MEG is a nascent technology and, to realise its potential, it must be shown to facilitate key neuroscientific measurements, such as the characterisation of brain networks. Networks, and the connectivities that underlie them, have become a core area of neuroscientific investigation, and their importance is underscored by many demonstrations of their disruption in brain disorders. Consequently, a demonstration of network measurements using OPM-MEG would be a significant step forward. Here, we aimed to show that a wearable 50-channel OPM-MEG system enables characterisation of the electrophysiological connectome. To this end, we measured connectivity in the resting state and during a visuo-motor task, using both OPM-MEG and a state-of-the-art 275-channel cryogenic MEG device. Our results show that resting-state connectome matrices from OPM and cryogenic systems exhibit a high degree of similarity, with correlation values >70%. In addition, in task data, similar differences in connectivity between individuals (scanned multiple times) were observed in cryogenic and OPM-MEG data, again demonstrating the fidelity of the OPM-MEG device. This is the first demonstration of network connectivity measured using OPM-MEG, and results add weight to the argument that OPMs will ultimately supersede cryogenic sensors for MEG measurement.
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