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The Very Large Array Sky Survey (VLASS) is a synoptic, all-sky radio sky survey with a unique combination of high angular resolution ( 2 5), sensitivity (a 1 goal of 70 Jy/beam in the coadded data), full linear Stokes polarimetry, time domain coverage, and wide bandwidth (2-4 GHz). The first observations began in 2017 September, and observing for the survey will finish in 2024. VLASS will use approximately 5500 hr of time on the Karl G. Jansky Very Large Array (VLA) to cover the whole sky visible to the VLA (decl. > −40°), a total of 33 885 deg 2 . The data will be taken in three epochs to allow the discovery of variable and transient radio sources. The survey is designed to engage radio astronomy experts, multi-wavelength astronomers, and citizen scientists alike. By utilizing an \"on the fly\" interferometry mode, the observing overheads are much reduced compared to a conventional pointed survey. In this paper, we present the science case and observational strategy for the survey, and also results from early survey observations.

Theoretical models and numerical simulations have established a framework of galaxy evolution in which galaxies merge and create dual supermassive black holes (with separations of one to ten kiloparsecs), which eventually sink into the centre of the merger remnant, emit gravitational waves and coalesce. The merger also triggers star formation and supermassive black hole growth, and gas outflows regulate the stellar content 1 – 3 . Although this theoretical picture is supported by recent observations of starburst-driven and supermassive black hole-driven outflows 4 – 6 , it remains unclear how these outflows interact with the interstellar medium. Furthermore, the relative contributions of star formation and black hole activity to galactic feedback remain unknown 7 – 9 . Here we report observations of dual outflows in the central region of the prototypical merger NGC 6240. We find a black-hole-driven outflow of [O iii ] to the northeast and a starburst-driven outflow of Hα to the northwest. The orientations and positions of the outflows allow us to isolate them spatially and study their properties independently. We estimate mass outflow rates of 10 and 75 solar masses per year for the Hα bubble and the [O iii ] cone, respectively. Their combined mass outflow is comparable to the star formation rate 10 , suggesting that negative feedback on star formation is occurring. Observations of NGC 6240 show two differently driven outflows of different gases with a combined outflow rate comparable to the star formation rate, suggesting possible negative feedback on star formation.

Gas supply to the stars Star formation requires the presence of cold molecular gas, which makes up only a small fraction of the total mass of the Milky Way and nearby galaxies where only a few new stars are formed per year. To establish whether the rapid star formation occurring in distant massive galaxies reflects a greater supply of cold gas or a more efficient process of star formation, gas content was surveyed in massive-star-forming galaxies at two cosmic epochs — at redshifts of approximately 1.2 and 2.3, when the Universe was 40% and 24% of its current age. The results reveal that distant star-forming galaxies were indeed gas rich and that the star-formation efficiency is not strongly dependent on cosmic epoch. The average fraction of cold gas relative to total galaxy mass is three to ten times higher in distant galaxies than in today's massive spiral galaxies. Stars form from cold molecular interstellar gas, which is relatively rare in the local Universe, such that galaxies like the Milky Way form only a few new stars per year. However, typical massive galaxies in the distant Universe formed stars much more rapidly, suggesting that young galaxies were more rich in molecular gas. The results of a survey of molecular gas in samples of typical massive star-forming galaxies when the Universe was 40% and 24% of its current age now reveal that distant star-forming galaxies were indeed gas rich. Stars form from cold molecular interstellar gas. As this is relatively rare in the local Universe, galaxies like the Milky Way form only a few new stars per year. Typical massive galaxies in the distant Universe formed stars an order of magnitude more rapidly 1 , 2 . Unless star formation was significantly more efficient, this difference suggests that young galaxies were much more molecular-gas rich. Molecular gas observations in the distant Universe have so far largely been restricted to very luminous, rare objects, including mergers and quasars 3 , 4 , 5 , and accordingly we do not yet have a clear idea about the gas content of more normal (albeit massive) galaxies. Here we report the results of a survey of molecular gas in samples of typical massive-star-forming galaxies at mean redshifts < z > of about 1.2 and 2.3, when the Universe was respectively 40% and 24% of its current age. Our measurements reveal that distant star forming galaxies were indeed gas rich, and that the star formation efficiency is not strongly dependent on cosmic epoch. The average fraction of cold gas relative to total galaxy baryonic mass at z = 2.3 and z = 1.2 is respectively about 44% and 34%, three to ten times higher than in today’s massive spiral galaxies 6 . The slow decrease between z  ≈ 2 and z  ≈ 1 probably requires a mechanism of semi-continuous replenishment of fresh gas to the young galaxies.

This study investigated the involvement of inner speech limitations in the executive dysfunction associated with autism spectrum disorders (ASDs). Seventeen children with ASD and 18 controls, statistically-matched in age and IQ, performed a computer-based card sorting test (CST) to assess cognitive flexibility under four conditions: baseline, with articulatory suppression, with a concurrent mouthing task, and while verbalizing their strategies aloud. Articulatory suppression adversely affected CST performance for the control group but not the ASD group. The results additionally showed that overtly verbalizing strategies did not benefit the ASD children as it did the typically developing children. The findings thus provide further evidence that ASD children do not use inner speech to the same extent, or with the same effectiveness, as typically developing children when performing executive tasks.

Understanding how structural and functional alterations of individual tissues impact on whole-joint function is challenging, particularly in humans where direct invasive experimentation is difficult. Finite element (FE) computational models produce quantitative predictions of the mechanical and physiological behaviour of multiple tissues simultaneously, thereby providing a means to study changes that occur through healthy ageing and disease such as osteoarthritis (OA). As a result, significant research investment has been placed in developing such models of the human knee. Previous work has highlighted that model predictions are highly sensitive to the various inputs used to build them, particularly the mathematical definition of material properties of biological tissues. The goal of this systematic review is two-fold. First, we provide a comprehensive summation and evaluation of existing linear elastic material property data for human tibiofemoral joint tissues, tabulating numerical values as a reference resource for future studies. Second, we review efforts to model tibiofemoral joint mechanical behaviour through FE modelling with particular focus on how studies have sourced tissue material properties. The last decade has seen a renaissance in material testing fuelled by development of a variety of new engineering techniques that allow the mechanical behaviour of both soft and hard tissues to be characterised at a spectrum of scales from nano- to bulk tissue level. As a result, there now exists an extremely broad range of published values for human tibiofemoral joint tissues. However, our systematic review highlights gaps and ambiguities that mean quantitative understanding of how tissue material properties alter with age and OA is limited. It is therefore currently challenging to construct FE models of the knee that are truly representative of a specific age or disease-state. Consequently, recent tibiofemoral joint FE models have been highly generic in terms of material properties even relying on non-human data from multiple species. We highlight this by critically evaluating current ability to quantitatively compare and model (1) young and old and (2) healthy and OA human tibiofemoral joints. We suggest that future research into both healthy and diseased knee function will benefit greatly from a subject- or cohort-specific approach in which FE models are constructed using material properties, medical imagery and loading data from cohorts with consistent demographics and/or disease states.

Osteoarthritis is traditionally associated with cartilage degeneration although is now widely accepted as a whole-joint disease affecting the entire osteochondral unit; however site-specific cartilage and bone material properties during healthy ageing and disease are absent limiting our understanding. Cadaveric specimens (n = 12; 31–88 years) with grades 0–4 osteoarthritis, were dissected and spatially correlated cartilage, subchondral and trabecular bone samples (n = 8 per cadaver) were harvested from femoral and tibial localities. Nanoindentation was utilised to obtain cartilage shear modulus ( G ′) and bone elastic modulus ( E ). Cartilage G ′ is strongly correlated to age ( p  = 0.003) and osteoarthritis grade ( p  = 0.007). Subchondral bone E is moderately correlated to age ( p  = 0.072) and strongly correlated to osteoarthritis grade ( p  = 0.013). Trabecular bone E showed no correlation to age ( p  = 0.372) or osteoarthritis grade ( p  = 0.778). Changes to cartilage G ′ was significantly correlated to changes in subchondral bone E ( p  = 0.007). Results showed preferential medial osteoarthritis development and moderate correlations between cartilage G ′ and sample location ( p  = 0.083). Also demonstrated for the first time was significant correlations between site-matched cartilage and subchondral bone material property changes during progressive ageing and osteoarthritis, supporting the role of bone in disease initiation and progression. This clinically relevant data indicates a causative link with osteoarthritis and medial habitual loading.

IntroductionChronic stable angina is common and disabling. Cardiac rehabilitation is routinely offered to people following myocardial infarction or revascularisation procedures and has the potential to help people with chronic stable angina. However, there is insufficient evidence of effectiveness and cost-effectiveness for its routine use in this patient group. The objectives of this study are to compare the effectiveness and cost-effectiveness of the ‘Activate Your Heart’ cardiac rehabilitation programme for people with chronic stable angina compared with usual care.Methods and analysisACTIVATE is a multicentre, parallel-group, two-arm, superiority, pragmatic randomised controlled trial, with recruitment from primary and secondary care centres in England and Wales and a target sample size of 518 (1:1 allocation; allocation sequence by minimisation programme with built-in random element). The study uses secure web-based allocation concealment. The two treatments will be optimal usual care (control) and optimal usual care plus the ‘Activate Your Heart’ web-based cardiac rehabilitation programme (intervention). Outcome assessment and statistical analysis will be performed blinded; participants will be unblinded. Outcomes will be measured at baseline and at 6 and 12 months’ follow-up. Primary outcome will be the UK version of Seattle Angina Questionnaire (SAQ-UK), physical limitations domain at 12 months’ follow-up. Secondary outcomes will be the remaining two domains of SAQ-UK, dyspnoea, anxiety and depression, health utility, self-efficacy, physical activity and the incremental shuttle walk test. All safety events will be recorded, and serious adverse events assessed to determine whether they are related to the intervention and expected. Concurrent economic evaluation will be cost–utility analysis from health service perspective. An embedded process evaluation will determine the mechanisms and processes that explain the implementation and impacts of the cardiac rehabilitation programme.Ethics and disseminationNorth of Scotland National Health Service Research Ethics Committee approval, reference 21/NS/0115. Participants will provide written informed consent. Results will be disseminated by peer-reviewed publication.Trial registration numberISRCTN10054455.

Dupuytren's disease is a common fibroproliferative disease of the palmar fascia of the hand, with advanced cases treated surgically. Anti-TNF injection has undergone phase 2 trials and may be effective in slowing early-stage disease progression. Here we sought to determine how new synthesis of type I collagen in Dupuytren's differs from normal palmar fascia samples and to analyze the role of TNF in aberrant collagen synthesis. Model nonfibrotic but fibrous connective tissues were used to analyze active type I collagen protein synthesis in development, aging, and degenerative disease, where it was restricted to early development and ruptured tissue. Dupuytren's tissue was shown to actively synthesize type I collagen, including abnormal type I collagen homotrimer. TNF-α reduced COL1A2 gene expression only in the presence of serum in 2D cell culture and had opposing effects on collagen protein production in the presence or absence of serum. TNF-α had only limited effects in 3D tendon-like constructs. Anti-TNF did not reduce type I collagen synthesis in 3D tendon-like constructs or prevent type I collagen homotrimer synthesis in Dupuytren's tissue. Hence, modulation of the TNF-α pathway in Dupuytren's disease is unlikely to prevent the pathological collagen accumulation that is characteristic of fibrosis.

Graham Greene’s novella Loser Takes All has been unfairly ignored in the critical literature. Rather than the mere frivolity it is taken to be, it is a humorous examination of some serious theological issues. By means of an inversion of Pascal’s Great Wager, Greene makes the case that attempts to rationalize the mystery that is the object of our faith will cheapen and diminish that faith. In the course of so doing, he alludes to and has fun with his earlier works, particularly Brighton Rock , and critiques the inversion of the Wager by Albert Camus. He shows the influence of Miguel de Unamuno, who years later would influence Greene’s Monsignor Quixote . Greene also invokes a poem by Charles Baudelaire, which Greene has quoted in many works, that the possibility of damnation adds meaning to life, though it may drift into what von Balthasar called Greene’s indulgence of the mystique of sin.

Cruciate ligaments (CL) of the knee joint are injured following trauma or aging. MicroRNAs (miRs) are potential therapeutic targets in musculoskeletal disorders, but there is little known about the role of miRs and their expression ligaments during aging. This study aimed to (1) identify if mice with normal physical activity, wild‐stock house mice are an appropriate model to study age‐related changes in the knee joint and (2) investigate the expression of miRs in aging murine cruciate ligaments. Knee joints were collected from 6 and 24 months old C57BL/6 and wild‐stock house mice (Mus musculus domesticus) for ligament and cartilage (OARSI) histological analysis. Expression of miR targets in CLs was determined in 6‐, 12‐, 24‐, and 30‐month‐old wild‐stock house mice, followed by the analysis of predicted mRNA target genes and Ingenuity Pathway Analysis. Higher CL and knee OARSI histological scores were found in 24‐month‐old wild‐stock house mice compared with 6‐ and 24‐month‐old C57BL/6 and 6‐month‐old wild‐stock house mice (p < 0.05). miR‐29a and miR‐34a were upregulated in 30‐month‐old wild‐stock house mice in comparison with 6‐, 12‐, and 24‐month‐old wild‐stock house mice (p < 0.05). Ingenuity Pathway Analysis on miR‐29a and 34a targets was associated with inflammation through interleukins, TGFβ and Notch genes, and p53 signaling. Collagen type I alpha 1 chain (COL1A1) correlated negatively with both miR‐29a (r = −0.35) and miR‐34a (r = −0.33). The findings of this study support wild‐stock house mice as an appropriate aging model for the murine knee joint. This study also indicated that miR‐29a and miR‐34a may be potential regulators of COL1A1 gene expression in murine CLs. This study aimed to investigate age‐related changes in microRNAs expression in mouse cruciate ligaments. Our findings demonstrate that the miRNAs were differentially expressed in cruciate ligaments from aging mice and are suggestive of important regulators of the extracellular matrix of murine cruciate ligaments during aging.