Statistics of Solar Wind Electron Breakpoint Energies Using Machine Learning Techniques

Solar wind electron velocity distributions at 1 au consist of a thermal "core" population and two suprathermal populations: "halo" and "strahl". The core and halo are quasi-isotropic, whereas the strahl typically travels radially outwards along the parallel and/or anti-parallel direction with respect to the interplanetary magnetic field. With Cluster-PEACE data, we analyse energy and pitch angle distributions and use machine learning techniques to provide robust classifications of these solar wind populations. Initially, we use unsupervised algorithms to classify halo and strahl differential energy flux distributions to allow us to calculate relative number densities, which are of the same order as previous results. Subsequently, we apply unsupervised algorithms to phase space density distributions over ten years to study the variation of halo and strahl breakpoint energies with solar wind parameters. In our statistical study, we find both halo and strahl suprathermal breakpoint energies display a significant increase with core temperature, with the halo exhibiting a more positive correlation than the strahl. We conclude low energy strahl electrons are scattering into the core at perpendicular pitch angles. This increases the number of Coulomb collisions and extends the perpendicular core population to higher energies, resulting in a larger difference between halo and strahl breakpoint energies at higher core temperatures. Statistically, the locations of both suprathermal breakpoint energies decrease with increasing solar wind speed. In the case of halo breakpoint energy, we observe two distinct profiles above and below 500 km/s. We relate this to the difference in origin of fast and slow solar wind.Comment: Published in Astronomy & Astrophysics, 11 pages, 10 figure

High-resolution evidence for dynamic transitional geomagnetic field behaviour from a Miocene reversal, McMurdo Sound, Ross Sea, Antarctica

We report a high-resolution record of a Miocene polarity transition (probably the Chron C6r-C6n transition) from glacimarine sediments in McMurdo Sound, Ross Sea, Antarctica, which is the first transition record reported from high southern latitudes. The transition is recorded in two parallel cores through a 10.7 m stratigraphic thickness. The sediments are interpreted as having been deposited in a marine environment under the influence of floating ice or seaward of a glacier terminus from which a large sediment load was delivered to the drill site. The core was recovered using rotary drilling, which precludes azimuthal orientation of the core and determination of a vector record of the field during the transition. However, constraints on transitional field behaviour are provided by the exceptional resolution of this record. Large-scale paleomagnetic inclination fluctuations in the two cores can be independently correlated with each other using magnetic susceptibility data, which suggests that the sediments are reliable recorders of geomagnetic field variations. Agreement between the two parallel transition records provides evidence for highly dynamic field behaviour, as suggested by numerous large-scale inclination changes (∼90◦) throughout the transition. These large-scale changes occur across stratigraphically narrow intervals, which is consistent with the suggestion of rapid field changes during transitions. In one intact portion of the core, where there is no apparent relative core rotation between samples, declinations and inclinations are consistent with the presence of a stable cluster of virtual geomagnetic poles within the transition (although the possibility that this cluster represents a rapid depositional event cannot be precluded). These observations are consistent with those from other high-resolution records and provide a rare detailed view of transitional field behaviour compared to most sedimentary records, which are not as thick and which appear to have been smoothed by sedimentary remanence acquisition processes

P37 Variable adherence to and effectiveness of a vancomycin continuous infusion protocol within ICUs at a London tertiary-care hospital: a single-centre retrospective service evaluation

BACKGROUND: Appropriate vancomycin dosing and therapeutic monitoring is important to optimize treatment for serious Gram-positive infections. In St George's Hospital ICUs, the treatment protocol is a loading dose (50  mL/min and 21–50  mL/min became supratherapeutic by their second day serum concentration. Obese and normal weight patients with CL(CR) >50  mL/min were consistently subtherapeutic. The mean time taken for non-therapeutic patients who continued treatment (n = 7) to become therapeutic after dose adjustments was 4 days. Patients (n = 17) were 82% male and of a mean age of 62 ± 17 years. Mean TBW was 79 ± 23 kg and mean CL(CR) 65 ± 48  mL/min. Sepsis was the most common vancomycin indication (65%). CONCLUSIONS: Multiple drug recording formats, plus adherence to and dosing of different aspects of the vancomycin protocol, requires review. This is to ensure accurate vancomycin administration documentation and that therapeutic concentrations are achieved more rapidly and consistently, whilst minimizing toxicity. A quality improvement project has been instigated to focus on protocol education, accessibility and improving IT infrastructure. Increased patient volume of distribution and renal function variability within the ICU population adds complexity to vancomycin pharmacokinetics. Research into pharmacokinetic models better representing the local ICU population and AUC(24) drug monitoring is being explored based on recent international guidance.(1

Using Dimensionality Reduction and Clustering Techniques to Classify Space Plasma Regimes

Collisionless space plasma environments are typically characterized by distinct particle populations. Although moments of their velocity distribution functions help in distinguishing different plasma regimes, the distribution functions themselves provide more comprehensive information about the plasma state, especially at times when the distribution function includes non-thermal effects. Unlike moments, however, distribution functions are not easily characterized by a small number of parameters, making their classification more difficult to achieve. In order to perform this classification, we propose to distinguish between the different plasma regions by applying dimensionality reduction and clustering methods to electron distributions in pitch angle and energy space. We utilize four separate algorithms to achieve our plasma classifications: autoencoders, principal component analysis, mean shift, and agglomerative clustering. We test our classification algorithms by applying our scheme to data from the Cluster-Plasma Electron and Current Experiment instrument measured in the Earth’s magnetotail. Traditionally, it is thought that the Earth’s magnetotail is split into three different regions (the plasma sheet, the plasma sheet boundary layer, and the lobes), that are primarily defined by their plasma characteristics. Starting with the ECLAT database with associated classifications based on the plasma parameters, we identify eight distinct groups of distributions, that are dependent upon significantly more complex plasma and field dynamics. By comparing the average distributions as well as the plasma and magnetic field parameters for each region, we relate several of the groups to different plasma sheet populations, and the rest we attribute to the plasma sheet boundary layer and the lobes. We find clear distinctions between each of our classified regions and the ECLAT results. The automated classification of different regions in space plasma environments provides a useful tool to identify the physical processes governing particle populations in near-Earth space. These tools are model independent, providing reproducible results without requiring the placement of arbitrary thresholds, limits or expert judgment. Similar methods could be used onboard spacecraft to reduce the dimensionality of distributions in order to optimize data collection and downlink resources in future missions

Constraining suprathermal electron evolution in a Parker spiral field with Cassini observations

Suprathermal electrons in the solar wind consist of the ‘halo’, present at all pitch angles, and the ‘strahl’ which is a field‐aligned, beam‐like population. Examining the heliospheric evolution of strahl beams is key to understanding the in‐transit processing of solar wind suprathermal electrons, in particular, to identify electron scattering mechanisms and to establish the origin of the halo population. Not only does this have significant implications with regard to the kinetic processes occurring within the solar wind but also its thermodynamic evolution, as the the suprathermal electrons carry the majority of the solar wind heat flux. In this investigation, an established model for suprathermal electron evolution in a Parker spiral interplanetary magnetic field (IMF) is adapted from its original use. The model is constrained using solar wind strahl observed by the Cassini mission on its interplanetary journey to Saturn. The effects of large scale IMF geometry due to different solar wind velocities and application of different electron scattering factors are examined. It is found that that slow solar wind speeds provide the closest match to the strahl width observations, both in terms of radial distance and electron energy trends, and that predominantly slower solar wind speeds were therefore likely observed by the Cassini mission en‐route to Saturn. It is necessary to include a strahl scattering factor which increases with electron energy in order to match observations, indicating that the strahl scattering mechanism must have an inherent energy dependence

Genome-wide association study of primary tooth eruption identifies pleiotropic loci associated with height and craniofacial distances

Twin and family studies indicate that the timing of primary tooth eruption is highly heritable, with estimates typically exceeding 80%. To identify variants involved in primary tooth eruption we performed a population based genome-wide association study of ‘age at first tooth’ and ‘number of teeth’ using 5998 and 6609 individuals respectively from the Avon Longitudinal Study of Parents and Children (ALSPAC) and 5403 individuals from the 1966 Northern Finland Birth Cohort (NFBC1966). We tested 2,446,724 SNPs imputed in both studies. Analyses were controlled for the effect of gestational age, sex and age of measurement. Results from the two studies were combined using fixed effects inverse variance meta-analysis. We identified a total of fifteen independent loci, with ten loci reaching genome-wide significance (p<5x10−8) for ‘age at first tooth’ and eleven loci for ‘number of teeth’. Together these associations explain 6.06% of the variation in ‘age of first tooth’ and 4.76% of the variation in ‘number of teeth’. The identified loci included eight previously unidentified loci, some containing genes known to play a role in tooth and other developmental pathways, including a SNP in the protein-coding region of BMP4 (rs17563, P= 9.080x10−17). Three of these loci, containing the genes HMGA2, AJUBA and ADK, also showed evidence of association with craniofacial distances, particularly those indexing facial width. Our results suggest that the genome-wide association approach is a powerful strategy for detecting variants involved in tooth eruption, and potentially craniofacial growth and more generally organ development

Targeted 'Next-Generation' sequencing in anophthalmia and microphthalmia patients confirms SOX2, OTX2 and FOXE3 mutations

<p>Abstract</p> <p>Background</p> <p>Anophthalmia/microphthalmia (A/M) is caused by mutations in several different transcription factors, but mutations in each causative gene are relatively rare, emphasizing the need for a testing approach that screens multiple genes simultaneously. We used next-generation sequencing to screen 15 A/M patients for mutations in 9 pathogenic genes to evaluate this technology for screening in A/M.</p> <p>Methods</p> <p>We used a pooled sequencing design, together with custom single nucleotide polymorphism (SNP) calling software. We verified predicted sequence alterations using Sanger sequencing.</p> <p>Results</p> <p>We verified three mutations - c.542delC in S<it>OX2</it>, resulting in p.Pro181Argfs*22, p.Glu105X in <it>OTX2 </it>and p.Cys240X in <it>FOXE3</it>. We found several novel sequence alterations and SNPs that were likely to be non-pathogenic - p.Glu42Lys in <it>CRYBA4</it>, p.Val201Met in <it>FOXE3 </it>and p.Asp291Asn in <it>VSX2</it>. Our analysis methodology gave one false positive result comprising a mutation in <it>PAX6 </it>(c.1268A > T, predicting p.X423LeuextX*15) that was not verified by Sanger sequencing. We also failed to detect one 20 base pair (bp) deletion and one 3 bp duplication in <it>SOX2</it>.</p> <p>Conclusions</p> <p>Our results demonstrated the power of next-generation sequencing with pooled sample groups for the rapid screening of candidate genes for A/M as we were correctly able to identify disease-causing mutations. However, next-generation sequencing was less useful for small, intragenic deletions and duplications. We did not find mutations in 10/15 patients and conclude that there is a need for further gene discovery in A/M.</p

Association of a de novo 16q copy number variant with a phenotype that overlaps with Lenz microphthalmia and Townes-Brocks syndromes

<p>Abstract</p> <p>Background</p> <p>Anophthalmia and microphthalmia are etiologically and clinically heterogeneous. Lenz microphthalmia is a syndromic form that is typically inherited in an X-linked pattern, though the causative gene mutation is unknown. Townes-Brocks syndrome manifests thumb anomalies, imperforate anus, and ear anomalies. We present a 13-year-old boy with a syndromic microphthalmia phenotype and a clinical diagnosis of Lenz microphthalmia syndrome.</p> <p>Case Presentation</p> <p>The patient was subjected to clinical and molecular evaluation, including array CGH analysis. The clinical features included left clinical anophthalmia, right microphthalmia, anteriorly placed anus with fistula, chordee, ventriculoseptal defect, patent ductus arteriosus, posteriorly rotated ears, hypotonia, growth retardation with delayed bone age, and mental retardation. The patient was found to have an approximately 5.6 Mb deletion of 16q11.2q12.1 by microarray based-comparative genomic hybridization, which includes the <it>SALL1 </it>gene, which causes Townes-Brocks syndrome.</p> <p>Conclusions</p> <p>Deletions of 16q11.2q12.2 have been reported in several individuals, although those prior reports did not note microphthalmia or anophthalmia. This region includes <it>SALL1</it>, which causes Townes-Brocks syndrome. In retrospect, this child has a number of features that can be explained by the <it>SALL1 </it>deletion, although it is not clear if the microphthalmia is a rare feature of Townes-Brocks syndrome or caused by other mechanisms. These data suggest that rare copy number changes may be a cause of syndromic microphthalmia allowing a personalized genomic medicine approach to the care of patients with these aberrations.</p

Effect of novel technology-enabled multidimensional physical activity feedback in primary care patients at risk of chronic disease – the MIPACT study: A randomised controlled trial

© 2020 The Author(s). Background: Technological progress has enabled the provision of personalised feedback across multiple dimensions of physical activity that are important for health. Whether this multidimensional approach supports physical activity behaviour change has not yet been examined. Our objective was to examine the effectiveness of a novel digital system and app that provided multidimensional physical activity feedback combined with health trainer support in primary care patients identified as at risk of chronic disease. Methods: MIPACT was a parallel-group, randomised controlled trial that recruited patients at medium (≥10 and minimum clinically important difference, MCID). However, there was profound physical activity multidimensionality, and only a small proportion (5%) of patients had consistently low physical activity across all dimensions. Conclusion: In patients at risk of cardiovascular disease and/or type II diabetes, MIPACT did not increase mean physical activity. Using a sophisticated multidimensional digital approach revealed enormous heterogeneity in baseline physical activity in primary care patients, and practitioners may need to screen for low physical activity across dimensions rather than rely on disease-risk algorithms that are heavily influenced by age. Trial registration: This trial is registered with the ISRCTN registry (ISRCTN18008011; registration date 31 July 2013)

Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice

Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site- and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc1tm1a) that reduces mRNA to ∼10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1tm1a/tm1a). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1tm1a/tm1a embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice