The meta book and size-dependent properties of written language

Evidence is given for a systematic text-length dependence of the power-law index gamma of a single book. The estimated gamma values are consistent with a monotonic decrease from 2 to 1 with increasing length of a text. A direct connection to an extended Heap's law is explored. The infinite book limit is, as a consequence, proposed to be given by gamma = 1 instead of the value gamma=2 expected if the Zipf's law was ubiquitously applicable. In addition we explore the idea that the systematic text-length dependence can be described by a meta book concept, which is an abstract representation reflecting the word-frequency structure of a text. According to this concept the word-frequency distribution of a text, with a certain length written by a single author, has the same characteristics as a text of the same length pulled out from an imaginary complete infinite corpus written by the same author.Comment: 7 pages, 6 figures, 1 tabl

Thiol-Reactive PODS-Bearing Bifunctional Chelators for the Development of EGFR-Targeting [¹⁸F]AlF-Affibody Conjugates.

Site-selective bioconjugation of cysteine-containing peptides and proteins is currently achieved via a maleimide-thiol reaction (Michael addition). When maleimide-functionalized chelators are used and the resulting bioconjugates are subsequently radiolabeled, instability has been observed both during radiosynthesis and post-injection in vivo, reducing radiochemical yield and negatively impacting performance. Recently, a phenyloxadiazolyl methylsulfone derivative (PODS) was proposed as an alternative to maleimide for the site-selective conjugation and radiolabeling of proteins, demonstrating improved in vitro stability and in vivo performance. Therefore, we have synthesized two novel PODS-bearing bifunctional chelators (NOTA-PODS and NODAGA-PODS) and attached them to the EGFR-targeting affibody molecule ZEGFR:03115. After radiolabeling with the aluminum fluoride complex ([18F]AlF), both conjugates showed good stability in murine serum. When injected in high EGFR-expressing tumor-bearing mice, [18F]AlF-NOTA-PODS-ZEGFR:03115 and [18F]AlF-NODAGA-PODS-ZEGFR:03115 showed similar pharmacokinetics and a specific tumor uptake of 14.1 ± 5.3% and 16.7 ± 4.5% ID/g at 1 h post-injection, respectively. The current results are encouraging for using PODS as an alternative to maleimide-based thiol-selective bioconjugation reactions

M22: A [Fe/H] Abundance Range Revealed

Intermediate resolution spectra at the Ca II triplet have been obtained for 55 candidate red giants in the field of the globular cluster M22 with the VLT/FORS instrument. Spectra were also obtained for a number of red giants in standard globular clusters to provide a calibration of the observed line strengths with overall abundance [Fe/H]. For the 41 M22 member stars that lie within the V-V_HB bounds of the calibration, we find an abundance distribution that is substantially broader than that expected from the observed errors alone. We argue that this broad distribution cannot be the result of differential reddening. Instead we conclude that, as has long been suspected, M22 is similar to omega Cen in having an intrinsic dispersion in heavy element abundance. The observed M22 abundance distribution rises sharply to a peak at [Fe/H] = -1.9 with a broad tail to higher abundances: the highest abundance star in our sample has [Fe/H] = -1.45 dex. If the unusual properties of omega Cen have their origin in a scenario in which the cluster is the remnant nucleus of a disrupted dwarf galaxy, then such a scenario likely applies also to M22.Comment: 29 pages, 9 figures, accepted for publication in the Astrophysical Journa

Risk Adjustment In Neurocritical care (RAIN)--prospective validation of risk prediction models for adult patients with acute traumatic brain injury to use to evaluate the optimum location and comparative costs of neurocritical care: a cohort study.

OBJECTIVES: To validate risk prediction models for acute traumatic brain injury (TBI) and to use the best model to evaluate the optimum location and comparative costs of neurocritical care in the NHS. DESIGN: Cohort study. SETTING: Sixty-seven adult critical care units. PARTICIPANTS: Adult patients admitted to critical care following actual/suspected TBI with a Glasgow Coma Scale (GCS) score of < 15. INTERVENTIONS: Critical care delivered in a dedicated neurocritical care unit, a combined neuro/general critical care unit within a neuroscience centre or a general critical care unit outside a neuroscience centre. MAIN OUTCOME MEASURES: Mortality, Glasgow Outcome Scale - Extended (GOSE) questionnaire and European Quality of Life-5 Dimensions, 3-level version (EQ-5D-3L) questionnaire at 6 months following TBI. RESULTS: The final Risk Adjustment In Neurocritical care (RAIN) study data set contained 3626 admissions. After exclusions, 3210 patients with acute TBI were included. Overall follow-up rate at 6 months was 81%. Of 3210 patients, 101 (3.1%) had no GCS score recorded and 134 (4.2%) had a last pre-sedation GCS score of 15, resulting in 2975 patients for analysis. The most common causes of TBI were road traffic accidents (RTAs) (33%), falls (47%) and assault (12%). Patients were predominantly young (mean age 45 years overall) and male (76% overall). Six-month mortality was 22% for RTAs, 32% for falls and 17% for assault. Of survivors at 6 months with a known GOSE category, 44% had severe disability, 30% moderate disability and 26% made a good recovery. Overall, 61% of patients with known outcome had an unfavourable outcome (death or severe disability) at 6 months. Between 35% and 70% of survivors reported problems across the five domains of the EQ-5D-3L. Of the 10 risk models selected for validation, the best discrimination overall was from the International Mission for Prognosis and Analysis of Clinical Trials in TBI Lab model (IMPACT) (c-index 0.779 for mortality, 0.713 for unfavourable outcome). The model was well calibrated for 6-month mortality but substantially underpredicted the risk of unfavourable outcome at 6 months. Baseline patient characteristics were similar between dedicated neurocritical care units and combined neuro/general critical care units. In lifetime cost-effectiveness analysis, dedicated neurocritical care units had higher mean lifetime quality-adjusted life-years (QALYs) at small additional mean costs with an incremental cost-effectiveness ratio (ICER) of £14,000 per QALY and incremental net monetary benefit (INB) of £17,000. The cost-effectiveness acceptability curve suggested that the probability that dedicated compared with combined neurocritical care units are cost-effective is around 60%. There were substantial differences in case mix between the 'early' (within 18 hours of presentation) and 'no or late' (after 24 hours) transfer groups. After adjustment, the 'early' transfer group reported higher lifetime QALYs at an additional cost with an ICER of £11,000 and INB of £17,000. CONCLUSIONS: The risk models demonstrated sufficient statistical performance to support their use in research but fell below the level required to guide individual patient decision-making. The results suggest that management in a dedicated neurocritical care unit may be cost-effective compared with a combined neuro/general critical care unit (although there is considerable statistical uncertainty) and support current recommendations that all patients with severe TBI would benefit from transfer to a neurosciences centre, regardless of the need for surgery. We recommend further research to improve risk prediction models; consider alternative approaches for handling unobserved confounding; better understand long-term outcomes and alternative pathways of care; and explore equity of access to postcritical care support for patients following acute TBI. FUNDING: The National Institute for Health Research Health Technology Assessment programme

Child height, health and human capital: evidence using genetic markers

Working Pape

Investigating white matter fibre density and morphology using fixel-based analysis

Voxel-based analysis of diffusion MRI data is increasingly popular. However, most white matter voxels contain contributions from multiple fibre populations (often referred to as crossing fibres), and therefore voxel-averaged quantitative measures (e.g. fractional anisotropy) are not fibre-specific and have poor interpretability. Using higher-order diffusion models, parameters related to fibre density can be extracted for individual fibre populations within each voxel (‘fixels’), and recent advances in statistics enable the multi-subject analysis of such data. However, investigating within-voxel microscopic fibre density alone does not account for macroscopic differences in the white matter morphology (e.g. the calibre of a fibre bundle). In this work, we introduce a novel method to investigate the latter, which we call fixel-based morphometry (FBM). To obtain a more complete measure related to the total number of white matter axons, information from both within-voxel microscopic fibre density and macroscopic morphology must be combined. We therefore present the FBM method as an integral piece within a comprehensive fixel-based analysis framework to investigate measures of fibre density, fibre-bundle morphology (cross-section), and a combined measure of fibre density and cross-section. We performed simulations to demonstrate the proposed measures using various transformations of a numerical fibre bundle phantom. Finally, we provide an example of such an analysis by comparing a clinical patient group to a healthy control group, which demonstrates that all three measures provide distinct and complementary information. By capturing information from both sources, the combined fibre density and cross-section measure is likely to be more sensitive to certain pathologies and more directly interpretable

Ca II Triplet Spectroscopy of Giants in SMC Star Clusters: Abundances, Velocities and the Age-Metallicity Relation

We have obtained spectra at the Ca II triplet of individual red giants in seven SMC star clusters whose ages range from ~4 to 12 Gyr. The spectra have been used to determine mean abundances for six of the star clusters to a typical precision of 0.12 dex. When combined with existing data for other objects, the resulting SMC age-metallicity relation is generally consistent with that for a simple model of chemical evolution, scaled to the present-day SMC mean abundance and gas mass fraction. Two of the clusters (Lindsay 113 and NGC 339), however, have abundances that ~0.5 dex lower than that expected from the mean age-metallicity relation. It is suggested that the formation of these clusters, which have ages of ~5 Gyr, may have involved the infall of uneriched gas, perhaps from the Magellanic Stream. The spectra also yield radial velocities for the seven clusters. The resulting velocity dispersion is 16 +/- 4 km/sec, consistent with those of the SMC planetary nebula and carbon star populations.Comment: 28 pages including 4 figure

Redshift-Distance Survey of Early-type Galaxies. I. Sample Selection, Properties and Completeness

This is the first in a series of papers describing the recently completed all-sky redshift-distance survey of nearby early-type galaxies (ENEAR) carried out for peculiar velocity analysis. The sample is divided into two parts and consists of 1607 elliptical and lenticular galaxies with cz < 7000 km/s and with blue magnitudes brighter than m_B=14.5 (ENEARm), and of galaxies in clusters (ENEARc). Galaxy distances based on the Dn-sigma and Fundamental Plane (FP) relations are now available for 1359 and 1107 ENEARm galaxies, respectively, with roughly 80% based on new data gathered by our group. The Dn-sigma and FP template distance relations are derived by combining 569 and 431 galaxies in 28 clusters, respectively, of which about 60% are based on our new measurements. The ENEARm redshift-distance survey extends the earlier work of the 7S and the recent Tully-Fisher surveys sampling a comparable volume. In subsequent papers of this series we intend to use the ENEAR sample by itself or in combination with the SFI Tully-Fisher survey to analyze the properties of the local peculiar velocity field and to test how sensitive the results are to different sampling and to the distance indicators. We also anticipate that the homogeneous database assembled will be used for a variety of other applications and serve as a benchmark for similar studies at high-redshift.Comment: 43 pages, 15 figures, submitted to the Astronomical Journa