Seismic anisotropy as a constraint on composition in the lower crust

Our current interpretation of the composition of the middle and lower crust comes mainly from seismic observations, yet it remains a challenge to link seismic observations directly to composition. This is because isotropic seismic properties are similar across a range of compositions. Taking anisotropy into account allows for further refinement of our interpretation of composition provided that anisotropy is characterized for candidate rock types. This study uses electron backscatter diffraction (EBSD) measurements of crystallographic preferred orientation of minerals to calculate seismic anisotropy in samples of the Pelona-Orocopia-Rand (POR) schist from the Mojave region of southern California. The goals of this work are to characterize the seismic anisotropy of the POR schist and its relationship to observed lower crustal anisotropy in the region, and to refine predictions of lower crustal composition based on seismic anisotropy

Simplified model of local transit services

This paper discusses the development of a simplified model to efficiently represent local public transportation services in a large-scale travel demand model. The California Statewide Travel Demand Model (CSTDM) is a comprehensive model system designed and developed for use in transportation policy analysis and travel demand forecasting, including representation of both long and short distance transportation covering the entire state of California. A novel hybrid system is used to represent the full range of rail and bus transit services that are available. Rail services – including all long-distance rail, commuter rail and light rail services – are represented in the standard manner, using explicit node and link networks; the relevant in-vehicle and out-ofvehicle service characteristics for journeys are determined as standard skims of these networks. On-street bus services are not represented using explicit networks; rather, the relevant in-vehicle and out-of-vehicle service characteristics are determined using functions of other transportation network variables, land use descriptors and relevant policy indicators. These functions are simplified econometric models estimated using observations of transit service obtained from Google Transit Data Feeds. The network and simplified components are integrated in order to allow transit paths with both rail and on-street bus components to be considered by the various travel choice models included in the modelling framework. This hybrid system provides a suitable representation of transit for an area of such size. This facilitates consideration of transit service policies, while obviating the need for extensive transit coding, a daunting task for a large area

Mixing in the Solar Nebula: Implications for Isotopic Heterogeneity and Large-Scale Transport of Refractory Grains

The discovery of refractory grains amongst the particles collected from Comet 81P/Wild 2 by the Stardust spacecraft (Brownlee et al. 2006) provides the ground truth for large-scale transport of materials formed in high temperature regions close to the protosun outward to the comet-forming regions of the solar nebula. While accretion disk models driven by a generic turbulent viscosity have been invoked as a means to explain such large-scale transport, the detailed physics behind such an ``alpha'' viscosity remains unclear. We present here an alternative physical mechanism for large-scale transport in the solar nebula: gravitational torques associated with the transient spiral arms in a marginally gravitationally unstable disk, of the type that appears to be necessary to form gas giant planets. Three dimensional models are presented of the time evolution of self-gravitating disks, including radiative transfer and detailed equations of state, showing that small dust grains will be transported upstream and downstream (with respect to the mean inward flow of gas and dust being accreted by the central protostar) inside the disk on time scales of less than 1000 yr inside 10 AU. These models furthermore show that any initial spatial heterogeneities present (e.g., in short-lived isotopes such as 26Al) will be homogenized by disk mixing down to a level of ~10%, preserving the use of short-lived isotopes as accurate nebular chronometers, while simultaneously allowing for the spread of stable oxygen isotope ratios. This finite level of nebular spatial heterogeneity appears to be related to the coarse mixing achieved by spiral arms, with radial widths of order 1 AU, over time scales of ~1000 yrs.Comment: 22 pages, 10 figures. Earth & Planetary Science Letters, accepte

Cosmochemical Consequences of Particle Trajectories During FU Orionis Outbursts by the Early Sun

The solar nebula is thought to have undergone a number of episodes of FU Orionis outbursts during its early evolution. We present here the first calculations of the trajectories of particles in a marginally gravitationally unstable solar nebula during an FU Orionis outburst, which show that 0.1 to 10 cm-sized particles traverse radial distances of 10 AU or more, inward and outward, in less than 200 yrs, exposing the particles to temperatures from $\sim$ 60 K to $\sim$ 1500 K. Such trajectories can thus account for the discovery of refractory particles in comets. Refractory particles should acquire Wark-Lovering-like rims as they leave the highest temperature regions of the disk, and these rims should have significant variations in their stable oxygen isotope ratios. Particles are likely to be heavily modified or destroyed if they pass within 1 AU of the Sun, and so are only likely to survive if they formed in the final few FU Orionis outbursts, or were transported to the outer reaches of the solar system. Calcium, aluminum-rich inclusions (CAIs) from primitive meteorites are the oldest known solar system objects and have a very narrow age range. Most CAIs may have formed at the end of the FU Orionis outbursts phase, with an age range reflecting the period between the last few outbursts.Comment: 32 pages, 4 figures, in press, EPS

Increasing dietary oat fibre decreases the permeability of intestinal mucus

This study investigates the influence of the dietary fibre β-glucan on nutrient composition and mucus permeability. Pigs were fed a standard diet or a diet containing twice the β-glucan content for 3 days (n = 5 per group), followed by the collection of small intestinal mucus and tissue samples. Samples of the consumed diets were subjected to in vitro digestion to determine β-glucan release, nutrient profile and assessment of mucus permeability. In vitro digestion of the diets indicated that 90% of the β-glucan was released in the proximal small intestine. Measurements of intestinal mucus showed a reduction in permeability to 100 nm latex beads and also lipid from the digested enhanced β-glucan diet. The data from this study show for the first time that reducing mass transfer of bile and lipid through the intestinal mucus layer may be one way in which this decrease in bile reabsorption by soluble fibre is enabled

Genetic influences on disease course and severity, 30 years after a clinically isolated syndrome

Multiple sclerosis risk has a well-established polygenic component, yet the genetic contribution to disease course and severity remains unclear and difficult to examine. Accurately measuring disease progression requires long-term study of clinical and radiological outcomes with sufficient follow-up duration to confidently confirm disability accrual and multiple sclerosis phenotypes. In this retrospective study, we explore genetic influences on long-term disease course and severity; in a unique cohort of clinically isolated syndrome patients with homogenous 30-year disease duration, deep clinical phenotyping and advanced MRI metrics. Sixty-one clinically isolated syndrome patients [41 female (67%): 20 male (33%)] underwent clinical and MRI assessment at baseline, 1-, 5-, 10-, 14-, 20- and 30-year follow-up (mean age ± standard deviation: 60.9 ± 6.5 years). After 30 years, 29 patients developed relapsing-remitting multiple sclerosis, 15 developed secondary progressive multiple sclerosis and 17 still had a clinically isolated syndrome. Twenty-seven genes were investigated for associations with clinical outcomes [including disease course and Expanded Disability Status Scale (EDSS)] and brain MRI (including white matter lesions, cortical lesions, and brain tissue volumes) at the 30-year follow-up. Genetic associations with changes in EDSS, relapses, white matter lesions and brain atrophy (third ventricular and medullary measurements) over 30 years were assessed using mixed-effects models. HLA-DRB1*1501-positive (n = 26) patients showed faster white matter lesion accrual [+1.96 lesions/year (0.64-3.29), P = 3.8 × 10-3], greater 30-year white matter lesion volumes [+11.60 ml, (5.49-18.29), P = 1.27 × 10-3] and higher annualized relapse rates [+0.06 relapses/year (0.005-0.11), P = 0.031] compared with HLA-DRB1*1501-negative patients (n = 35). PVRL2-positive patients (n = 41) had more cortical lesions (+0.83 [0.08-1.66], P = 0.042), faster EDSS worsening [+0.06 points/year (0.02-0.11), P = 0.010], greater 30-year EDSS [+1.72 (0.49-2.93), P = 0.013; multiple sclerosis cases: +2.60 (1.30-3.87), P = 2.02 × 10-3], and greater risk of secondary progressive multiple sclerosis [odds ratio (OR) = 12.25 (1.15-23.10), P = 0.031] than PVRL2-negative patients (n = 18). In contrast, IRX1-positive (n = 30) patients had preserved 30-year grey matter fraction [+0.76% (0.28-1.29), P = 8.4 × 10-3], lower risk of cortical lesions [OR = 0.22 (0.05-0.99), P = 0.049] and lower 30-year EDSS [-1.35 (-0.87,-3.44), P = 0.026; multiple sclerosis cases: -2.12 (-0.87, -3.44), P = 5.02 × 10-3] than IRX1-negative patients (n = 30). In multiple sclerosis cases, IRX1-positive patients also had slower EDSS worsening [-0.07 points/year (-0.01,-0.13), P = 0.015] and lower risk of secondary progressive multiple sclerosis [OR = 0.19 (0.04-0.92), P = 0.042]. These exploratory findings support diverse genetic influences on pathological mechanisms associated with multiple sclerosis disease course. HLA-DRB1*1501 influenced white matter inflammation and relapses, while IRX1 (protective) and PVRL2 (adverse) were associated with grey matter pathology (cortical lesions and atrophy), long-term disability worsening and the risk of developing secondary progressive multiple sclerosis

The top 10 research priorities in cystic fibrosis developed by a partnership between people with CF and healthcare providers

There remain many treatment uncertainties in cystic fibrosis (CF). With limited resources, research should focus on questions which are most important to the CF community. We conducted a James Lind Alliance Priority Setting Partnership in CF. Research questions were elicited and then prioritised in successive surveys. A workshop agreed the final top 10. Online methods avoided cross infection and widened participation. The elicitation survey had 482 respondents (1080 questions) and prioritisation survey 677 respondents. Participants were drawn equally from the patient and clinical communities globally. We have achieved a consensus on 10 research priorities which will be attractive to funders

Sodium alginate decreases the permeability of intestinal mucus

In the small intestine the nature of the environment leads to a highly heterogeneous mucus layer primarily composed of the MUC2 mucin. We set out to investigate whether the soluble dietary fibre sodium alginate could alter the permeability of the mucus layer. The alginate was shown to freely diffuse into the mucus and to have minimal effect on the bulk rheology when added at concentrations below 0.1%. Despite this lack of interaction between the mucin and alginate, the addition of alginate had a marked effect on the diffusion of 500 nm probe particles, which decreased as a function of increasing alginate concentration. Finally, we passed a protein stabilised emulsion through a simulation of oral, gastric and small intestinal digestion. We subsequently showed that the addition of 0.1% alginate to porcine intestinal mucus decreased the diffusion of fluorescently labelled lipid present in the emulsion digesta. This reduction may be sufficient to reduce problems associated with high rates of lipid absorption such as hyperlipidaemia

Developmental programming of polycystic ovary syndrome (PCOS): prenatal androgens establish pancreatic islet ?/? cell ratio and subsequent insulin secretion

Exogenous androgenic steroids applied to pregnant sheep programmes a PCOS-like phenotype in female offspring. Via ultrasound guidance we applied steroids directly to ovine fetuses at d62 and d82 of gestation, and examined fetal (day 90 gestation) and postnatal (11 months old) pancreatic structure and function. Of three classes of steroid agonists applied (androgen - Testosterone propionate (TP), estrogen - Diethystilbesterol (DES) and glucocorticoid - Dexamethasone (DEX)), only androgens (TP) caused altered pancreatic development. Beta cell numbers were significantly elevated in prenatally androgenised female fetuses (P=0.03) (to approximately the higher numbers found in male fetuses), whereas alpha cell counts were unaffected, precipitating decreased alpha:beta cell ratios in the developing fetal pancreas (P=0.001), sustained into adolescence (P=0.0004).In adolescence basal insulin secretion was significantly higher in female offspring from androgen-excess pregnancies (P=0.045), and an exaggerated, hyperinsulinaemic response to glucose challenge (P=0.0007) observed, whereas prenatal DES or DEX treatment had no effects upon insulin secretion. Postnatal insulin secretion correlated with beta cell numbers (P=0.03). We conclude that the pancreas is a primary locus of androgenic stimulation during development, giving rise to postnatal offspring whose pancreas secreted excess insulin due to excess beta cells in the presence of a normal number of alpha cells

Deep gray matter volume loss drives disability worsening in multiple sclerosis.

OBJECTIVE: Gray matter (GM) atrophy occurs in all multiple sclerosis (MS) phenotypes. We investigated whether there is a spatiotemporal pattern of GM atrophy that is associated with faster disability accumulation in MS. METHODS: We analyzed 3,604 brain high-resolution T1-weighted magnetic resonance imaging scans from 1,417 participants: 1,214 MS patients (253 clinically isolated syndrome [CIS], 708 relapsing-remitting [RRMS], 128 secondary-progressive [SPMS], and 125 primary-progressive [PPMS]), over an average follow-up of 2.41 years (standard deviation [SD] = 1.97), and 203 healthy controls (HCs; average follow-up = 1.83 year; SD = 1.77), attending seven European centers. Disability was assessed with the Expanded Disability Status Scale (EDSS). We obtained volumes of the deep GM (DGM), temporal, frontal, parietal, occipital and cerebellar GM, brainstem, and cerebral white matter. Hierarchical mixed models assessed annual percentage rate of regional tissue loss and identified regional volumes associated with time-to-EDSS progression. RESULTS: SPMS showed the lowest baseline volumes of cortical GM and DGM. Of all baseline regional volumes, only that of the DGM predicted time-to-EDSS progression (hazard ratio = 0.73; 95% confidence interval, 0.65, 0.82; p < 0.001): for every standard deviation decrease in baseline DGM volume, the risk of presenting a shorter time to EDSS worsening during follow-up increased by 27%. Of all longitudinal measures, DGM showed the fastest annual rate of atrophy, which was faster in SPMS (-1.45%), PPMS (-1.66%), and RRMS (-1.34%) than CIS (-0.88%) and HCs (-0.94%; p < 0.01). The rate of temporal GM atrophy in SPMS (-1.21%) was significantly faster than RRMS (-0.76%), CIS (-0.75%), and HCs (-0.51%). Similarly, the rate of parietal GM atrophy in SPMS (-1.24-%) was faster than CIS (-0.63%) and HCs (-0.23%; all p values <0.05). Only the atrophy rate in DGM in patients was significantly associated with disability accumulation (beta = 0.04; p < 0.001). INTERPRETATION: This large, multicenter and longitudinal study shows that DGM volume loss drives disability accumulation in MS, and that temporal cortical GM shows accelerated atrophy in SPMS than RRMS. The difference in regional GM atrophy development between phenotypes needs to be taken into account when evaluating treatment effect of therapeutic interventions. Ann Neurol 2018;83:210-222