Dynamics of the Lyman alpha and C IV emitting gas in 3C 273

In this paper we study the variability properties of the Lyman alpha and C IV emission lines in 3C273 using archival IUE observations. Our data show for the first time the existence of variability on time scales of several years. We study the spatial distribution and the velocity field of the emitting gas by performing detailed analyses on the line variability using correlations, 1D and 2D response functions, and principal component analysis. In both lines we find evidence for two components, one which has the dynamic properties of gas in Keplerian motion around a black hole with a mass of the order of 10^9 Mo, and one which is characterized by high, blue-shifted velocities at large lag. There is no indication of the presence of optically thick emission medium neither in the Lya, nor in the Civ response functions. The component characterized by blue-shifted velocities, which is comparatively much stronger in Civ than in Lya, is more or less compatible with being the result of gas falling towards the central black hole with free-fall acceleration. We propose however that the line emission at high, blue-shifted velocities is better explained in terms of entrainment of gas clouds by the jet. This gas is therefore probably collisionally excited as a result of heating due to the intense infrared radiation from the jet, which would explain the strength of this component in Civ relative to Lya. This phenomenon might be a signature of disk-jet interaction.Comment: 16 pages, 10 figures. Accepted for publication in ApJ. Uses aaste

The Age-Related Association of Movement in Irish Adolescent Youth

(1) Background: Research has shown that post-primary Irish youth are insufficiently active and fail to reach a level of proficiency across basic movement skills. The purpose of the current research was to gather cross-sectional baseline data on Irish adolescent youth, specifically the prevalence of movement skills and patterns, in order to generate an overall perspective of movement within the first three years (Junior Certificate level) of post-primary education. (2) Methods: Data were collected on adolescents (N = 181; mean age: 14.42 ± 0.98 years), attending two, mixed-gender schools. Data collection included 10 fundamental movement skills (FMS) and the seven tests within the Functional Movement Screen (FMS™). The data set was analysed using the Statistical Package for Social Sciences (SPSS) version 20.0 for Windows. (3) Results: Overall, levels of actual mastery within fundamental and functional movement were low. There were statistically significant age-related differences observed, with a progressive decline as age increased in both the object control (p = 0.002) FMS sub-domain, and the in-line lunge (p = 0.048) test of the FMS™. (4) Conclusion: In summary, we found emerging evidence that school year group is significantly associated with mastery of movement skills and patterns. Results from the current study suggest that developing a specifically tailored movement-oriented intervention would be a strategic step towards improving the low levels of adolescent fundamental and functional movement proficiency

Do Irish adolescents have adequate functional movement skill and confidence?

Recent research has shown that post-primary Irish youth are insufficiently active and fail to reach a level of proficiency across basic fundamental movement skills. The purpose of the current research was to gather cross-sectional data on adolescent youth, differentiated by gender, specifically to inform the development of a targeted movement-oriented intervention. Data were collected on adolescents (N=219; mean age: 14.45 ± 0.96 years), within two, mixed gender schools. Data collection included actual and perceived movement measurements; comprising of fundamental movement skills, the functional movement screen, perceived movement confidence and perceived functional confidence. Overall, levels of actual mastery within fundamental and functional movement were low, with significant gender differences observed. Adolescent males scored higher in the overall fundamental movement skill domain (male mean score = 70.87 ± 7.05; female mean score = 65.53 ± 7.13), yet lower within the functional movement screen (male mean score = 13.58 ± 2.59), in comparison to their female counterparts (female mean score = 14.70 ± 2.16). There were high levels of perceived confidence reported within fundamental and functional movement scales. Future intervention strategies should combat the low levels of actual movement skill proficiency, whilst identifying the reasons for higher perceived movement confidence within adolescents

Implantable cardioverter defibrillators for the treatment of arrhythmias and cardiac resynchronisation therapy for the treatment of heart failure: systematic review and economic evaluation

Background This assessment updates and expands on two previous technology assessments that evaluated implantable cardioverter defibrillators (ICDs) for arrhythmias and cardiac resynchronisation therapy (CRT) for heart failure (HF). Objectives To assess the clinical effectiveness and cost-effectiveness of ICDs in addition to optimal pharmacological therapy (OPT) for people at increased risk of sudden cardiac death (SCD) as a result of ventricular arrhythmias despite receiving OPT; to assess CRT with or without a defibrillator (CRT-D or CRT-P) in addition to OPT for people with HF as a result of left ventricular systolic dysfunction (LVSD) and cardiac dyssynchrony despite receiving OPT; and to assess CRT-D in addition to OPT for people with both conditions. Data sources Electronic resources including MEDLINE, EMBASE and The Cochrane Library were searched from inception to November 2012. Additional studies were sought from reference lists, clinical experts and manufacturers’ submissions to the National Institute for Health and Care Excellence. Review methods Inclusion criteria were applied by two reviewers independently. Data extraction and quality assessment were undertaken by one reviewer and checked by a second. Data were synthesised through narrative review and meta-analyses. For the three populations above, randomised controlled trials (RCTs) comparing (1) ICD with standard therapy, (2) CRT-P or CRT-D with each other or with OPT and (3) CRT-D with OPT, CRT-P or ICD were eligible. Outcomes included mortality, adverse events and quality of life. A previously developed Markov model was adapted to estimate the cost-effectiveness of OPT, ICDs, CRT-P and CRT-D in the three populations by simulating disease progression calculated at 4-weekly cycles over a lifetime horizon. Results A total of 4556 references were identified, of which 26 RCTs were included in the review: 13 compared ICD with medical therapy, four compared CRT-P/CRT-D with OPT and nine compared CRT-D with ICD. ICDs reduced all-cause mortality in people at increased risk of SCD, defined in trials as those with previous ventricular arrhythmias/cardiac arrest, myocardial infarction (MI) > 3 weeks previously, non-ischaemic cardiomyopathy (depending on data included) or ischaemic/non-ischaemic HF and left ventricular ejection fraction ≤ 35%. There was no benefit in people scheduled for coronary artery bypass graft. A reduction in SCD but not all-cause mortality was found in people with recent MI. Incremental cost-effectiveness ratios (ICERs) ranged from £14,231 per quality-adjusted life-year (QALY) to £29,756 per QALY for the scenarios modelled. CRT-P and CRT-D reduced mortality and HF hospitalisations, and improved other outcomes, in people with HF as a result of LVSD and cardiac dyssynchrony when compared with OPT. The rate of SCD was lower with CRT-D than with CRT-P but other outcomes were similar. CRT-P and CRT-D compared with OPT produced ICERs of £27,584 per QALY and £27,899 per QALY respectively. The ICER for CRT-D compared with CRT-P was £28,420 per QALY. In people with both conditions, CRT-D reduced the risk of all-cause mortality and HF hospitalisation, and improved other outcomes, compared with ICDs. Complications were more common with CRT-D. Initial management with OPT alone was most cost-effective (ICER £2824 per QALY compared with ICD) when health-related quality of life was kept constant over time. Costs and QALYs for CRT-D and CRT-P were similar. The ICER for CRT-D compared with ICD was £27,195 per QALY and that for CRT-D compared with OPT was £35,193 per QALY. Limitations Limitations of the model include the structural assumptions made about disease progression and treatment provision, the extrapolation of trial survival estimates over time and the assumptions made around parameter values when evidence was not available for specific patient groups. Conclusions In people at risk of SCD as a result of ventricular arrhythmias and in those with HF as a result of LVSD and cardiac dyssynchrony, the interventions modelled produced ICERs of < £30,000 per QALY gained. In people with both conditions, the ICER for CRT-D compared with ICD, but not CRT-D compared with OPT, was < £30,000 per QALY, and the costs and QALYs for CRT-D and CRT-P were similar. A RCT comparing CRT-D and CRT-P in people with HF as a result of LVSD and cardiac dyssynchrony is required, for both those with and those without an ICD indication. A RCT is also needed into the benefits of ICD in non-ischaemic cardiomyopathy in the absence of dyssynchrony. Study registration This study is registered as PROSPERO number CRD42012002062. Funding The National Institute for Health Research Health Technology Assessment programme

Strengthening and stretching for rheumatoid arthritis of the hand (SARAH). A randomised controlled trial and economic evaluation

Study registration: Current Controlled Trials ISRCTN 89936343.Background - The effectiveness of exercise for improving hand and wrist function in people with rheumatoid arthritis (RA) is uncertain. Objectives - The study aims were (1) to estimate the clinical effectiveness and cost-effectiveness of adding an optimised exercise programme for hands and upper limbs to standard care for patients with RA; and (2) to qualitatively describe the experience of participants in the trial with a particular emphasis on acceptability of the intervention, exercise behaviours and reasons for adherence/non-adherence.This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 19. See the NIHR Journals Library website for further project information. This report has been developed in association with the NIHR Collaboration for Leadership in Applied Health Research and Care Oxford and the NIHR Biomedical Research Unit Funding Scheme. This project benefited from facilities funded through Birmingham Science City Translational Medicine Clinical Research and Infrastructure Trials Platform, with support from Advantage West Midlands

The paternal transition entails neuroanatomic adaptations that are associated with the father's brain response to his infant cues

The transition into fatherhood is a life-changing event that requires substantial psychological adaptations. In families that include a father figure, sensitive paternal behavior has been shown to positively impact the infant's development. Yet, studies exploring the neuroanatomic adaptations of men in their transition into fatherhood are scarce. The present study used surface-based methods to reanalyze a previously published prospective magnetic resonance imaging dataset comprised of 20 first-time fathers (preconception-to-postpartum) and 17 childless men. We tested if the transition into fatherhood entailed changes in cortical volume, thickness, and area and whether these changes were related to 2 indicators of paternal experience. Specifically, we tested if such changes were associated with (1) the baby's age and/or (2) the fathers' brain activity in response to pictures of their babies compared with an unknown baby. Results indicated that first-time fathers exhibited a significant reduction in cortical volume and thickness of the precuneus. Moreover, higher volume reduction and cortical thinning were associated with stronger brain responses to pictures of their own baby in parental brain regions. This is the first study showing preconception-to-postpartum neuroanatomical adaptations in first-time fathers associated with the father's brain response to cues of his infant.Ministerio de Ciencia, Innovación y Universidades project (RTI2018-093952-B-100); Instituto de Salud Carlos III projects (CP16/00096 and PI17/00064); cofunded by European Regional Development Fund, "A way of making Europe" and by "La Caixa" Foundation under the project code LCF/PR/HR19/52160001, and by the European Research Council under the project code 883069. The project ASPIDE has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement number 801091. M.M.G. and S.S.C. were funded by Ministerio de Ciencia, Innovación y Universidades, Instituto de Salud Carlos III (PFIS contract FI18/00255 and Miguel Servet Type I research contract CP16/00096, respectively), and cofunded by European Social Fund "Investing in your future". The Centro Nacional de Investigaciones Cardiovasculares is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Quantitative trait loci conferring grain mineral nutrient concentrations in durum wheat 3 wild emmer wheat RIL population

Mineral nutrient malnutrition, and particularly deficiency in zinc and iron, afflicts over 3 billion people worldwide. Wild emmer wheat, Triticum turgidum ssp. dicoccoides, genepool harbors a rich allelic repertoire for mineral nutrients in the grain. The genetic and physiological basis of grain protein, micronutrients (zinc, iron, copper and manganese) and macronutrients (calcium, magnesium, potassium, phosphorus and sulfur) concentration was studied in tetraploid wheat population of 152 recombinant inbred lines (RILs), derived from a cross between durum wheat (cv. Langdon) and wild emmer (accession G18-16). Wide genetic variation was found among the RILs for all grain minerals, with considerable transgressive effect. A total of 82 QTLs were mapped for 10 minerals with LOD score range of 3.2–16.7. Most QTLs were in favor of the wild allele (50 QTLs). Fourteen pairs of QTLs for the same trait were mapped to seemingly homoeologous positions, reflecting synteny between the A and B genomes. Significant positive correlation was found between grain protein concentration (GPC), Zn, Fe and Cu, which was supported by significant overlap between the respective QTLs, suggesting common physiological and/or genetic factors controlling the concentrations of these mineral nutrients. Few genomic regions (chromosomes 2A, 5A, 6B and 7A) were found to harbor clusters of QTLs for GPC and other nutrients. These identified QTLs may facilitate the use of wild alleles for improving grain nutritional quality of elite wheat cultivars, especially in terms of protein, Zn and Fe

Gamma Ray Bursts Flares detected and observed by the Swift Satellite

The detection of flares with the Swift satellite triggered a lot of bservational and theoretical interest in these phenomena. As a consequence a large analysis effort started within the community to characterize the phenomenon and at the same time a variety of theoretical speculations have been proposed to explain it. In this presentation we discuss part of the results we obtained analyzing a first statistical sample of GRBs observed with Swift. The first goal of this research is very simple: derive those observational properties that could distinguish between internal and external shock and between an ever active central engine and delayed shocks (refreshing) related to a very small initial Lorentz bulk factor. We discuss first the method of analysis and the morphology evidencing the similarities such flares have with the prompt emission pulses. We conclude that GRB flares are due to internal shocks and leave still open the question of whether or not the central engine is active for a time of the order of 105 seconds after the prompt emission.Comment: Proceedings of the Beijing COSPAR Assembly 2006; submitted Nov 2, 200

A metabolomics cell-based approach for anticipating and investigating drug-induced liver injury

In preclinical stages of drug development, anticipating potential adverse drug effects such as toxicity is an important issue for both saving resources and preventing public health risks. Current in vitro cytotoxicity tests are restricted by their predictive potential and their ability to provide mechanistic information. This study aimed to develop a metabolomic mass spectrometry-based approach for the detection and classification of drug-induced hepatotoxicity. To this end, the metabolite profiles of human derived hepatic cells (i.e., HepG2) exposed to different well-known hepatotoxic compounds acting through different mechanisms (i.e., oxidative stress, steatosis, phospholipidosis, and controls) were compared by multivariate data analysis, thus allowing us to decipher both common and mechanism-specific altered biochemical pathways. Briefly, oxidative stress damage markers were found in the three mechanisms, mainly showing altered levels of metabolites associated with glutathione and γ-glutamyl cycle. Phospholipidosis was characterized by a decreased lysophospholipids to phospholipids ratio, suggestive of phospholipid degradation inhibition. Whereas, steatosis led to impaired fatty acids β-oxidation and a subsequent increase in triacylglycerides synthesis. The characteristic metabolomic profiles were used to develop a predictive model aimed not only to discriminate between non-toxic and hepatotoxic drugs, but also to propose potential drug toxicity mechanism(s)

Visual hallucinations in the psychosis spectrum and comparative information from neurodegenerative disorders and eye disease

Much of the research on visual hallucinations (VHs) has been conducted in the context of eye disease and neurodegenerative conditions, but little is known about these phenomena in psychiatric and nonclinical populations. The purpose of this article is to bring together current knowledge regarding VHs in the psychosis phenotype and contrast this data with the literature drawn from neurodegenerative disorders and eye disease. The evidence challenges the traditional views that VHs are atypical or uncommon in psychosis. The weighted mean for VHs is 27% in schizophrenia, 15% in affective psychosis, and 7.3% in the general community. VHs are linked to a more severe psychopathological profile and less favorable outcome in psychosis and neurodegenerative conditions. VHs typically co-occur with auditory hallucinations, suggesting a common etiological cause. VHs in psychosis are also remarkably complex, negative in content, and are interpreted to have personal relevance. The cognitive mechanisms of VHs in psychosis have rarely been investigated, but existing studies point to source-monitoring deficits and distortions in top-down mechanisms, although evidence for visual processing deficits, which feature strongly in the organic literature, is lacking. Brain imaging studies point to the activation of visual cortex during hallucinations on a background of structural and connectivity changes within wider brain networks. The relationship between VHs in psychosis, eye disease, and neurodegeneration remains unclear, although the pattern of similarities and differences described in this review suggests that comparative studies may have potentially important clinical and theoretical implications. © 2014 The Author