The Hot Interstellar Medium in Normal Elliptical Galaxies III: The Thermal Structure of the Gas

This is the third paper in a series analyzing X-ray emission from the hot interstellar medium in a sample of 54 normal elliptical galaxies observed by Chandra, focusing on 36 galaxies with sufficient signal to compute radial temperature profiles. We distinguish four qualitatively different types of profile: positive gradient (outwardly rising), negative gradients (falling), quasi-isothermal (flat) and hybrid (falling at small radii, then rising). We measure the mean logarithmic temperature gradients in two radial regions: from 0--2 $J$-band effective radii $R_J$ (excluding the central point source), and from 2--$4R_J$. We find the outer gradient to be uncorrelated with intrinsic host galaxy properties, but strongly influenced by the environment: galaxies in low-density environments tend to show negative outer gradients, while those in high-density environments show positive outer gradients, suggesting influence of circumgalactic hot gas. The inner temperature gradient is unaffected by the environment but strongly correlated with intrinsic host galaxy characteristics: negative inner gradients are more common for smaller, optically faint, low radio-luminosity galaxies, whereas positive gradients are found in bright galaxies with stronger radio sources. There is no evidence for bimodality in the distribution of inner or outer gradients. We propose three scenarios to explain the inner temperature gradients: (1) Weak AGN heat the ISM locally, higher-luminosity AGN heat the system globally through jets inflating cavities at larger radii; (2) The onset of negative inner gradients indicates a declining importance of AGN heating relative to other sources, such as compressional heating or supernovae; (3) The variety of temperature profiles are snapshots of different stages of a time-dependent flow.Comment: 18 pages, emulateapj, 55 figures (36 online-only figures included in astro-ph version), submitted to Ap

Estimation of treatment policy estimands for continuous outcomes using off treatment sequential multiple imputation

The estimands framework outlined in ICH E9 (R1) describes the components needed to precisely define the effects to be estimated in clinical trials, which includes how post-baseline "intercurrent" events (IEs) are to be handled. In late-stage clinical trials, it is common to handle intercurrent events like "treatment discontinuation" using the treatment policy strategy and target the treatment effect on all outcomes regardless of treatment discontinuation. For continuous repeated measures, this type of effect is often estimated using all observed data before and after discontinuation using either a mixed model for repeated measures (MMRM) or multiple imputation (MI) to handle any missing data. In basic form, both of these estimation methods ignore treatment discontinuation in the analysis and therefore may be biased if there are differences in patient outcomes after treatment discontinuation compared to patients still assigned to treatment, and missing data being more common for patients who have discontinued treatment. We therefore propose and evaluate a set of MI models that can accommodate differences between outcomes before and after treatment discontinuation. The models are evaluated in the context of planning a phase 3 trial for a respiratory disease. We show that analyses ignoring treatment discontinuation can introduce substantial bias and can sometimes underestimate variability. We also show that some of the MI models proposed can successfully correct the bias but inevitably lead to increases in variance. We conclude that some of the proposed MI models are preferable to the traditional analysis ignoring treatment discontinuation, but the precise choice of MI model will likely depend on the trial design, disease of interest and amount of observed and missing data following treatment discontinuation

Understanding differing outcomes from semantic and phonological interventions with children with word-finding difficulties: a group and case series study

Developmental Language Disorder occurs in up to 10% of children and many of these children have difficulty retrieving words in their receptive vocabulary. Such word-finding difficulties (WFD) can impact social development and educational outcomes. This research aims to develop the evidence-base for supporting children with WFD and inform the design and analysis of intervention studies. We included 20 children (age 6 to 8) with WFD each of whom participated in two interventions one targeting semantic attributes and the other phonological attributes of target words. The interventions, employing word-webs, were carefully constructed to facilitate direct comparison of outcome which was analysed at both group and case-series level. The study used a robust crossover design with pre-intervention baseline, between–intervention wash-out and post-intervention follow-up testing. We incorporated: matching of item sets on individual performance at baseline, independent randomisation of order of intervention and items to condition, blinding of assessor, evaluation of fidelity and control items. The interventions were clinically feasible, with weekly sessions over six weeks. Intervention improved children’s word-finding abilities with statistically significant change only during treatment phases of the study and not over baseline, wash-out or follow-up phases. For the group the semantic intervention resulted in a gain of almost twice as many items as the phonological intervention, a significant difference. However, children differed in their response to intervention. Importantly, case-series analysis revealed outcomes predictable on the basis of children’s theoretically driven language profiles. Taking account of individual profiles in determining choice of intervention would enable more children to benefit. The study provides new evidence to inform and refine clinical practice with this population. Future studies should be designed such that results can be analysed at both group and case series levels to extend theoretical understanding and optimise use of appropriate interventions

Intervening to alleviate word-finding difficulties in children: case series data and a computational modelling foundation

We evaluated a simple computational model of productive vocabulary acquisition, applied to simulating two case studies of 7-year-old children with developmental word-finding difficulties across four core behavioural tasks. Developmental models were created, which captured the deficits of each child. In order to predict the effects of intervention, we exposed the computational models to simulated behavioural interventions of two types, targeting the improvement of either phonological or semantic knowledge. The model was then evaluated by testing the predictions from the simulations against the actual results from an intervention study carried out with the two children. For one child it was predicted that the phonological intervention would be effective, and the semantic intervention would not. This was borne out in the behavioural study. For the second child, the predictions were less clear and depended on the nature of simulated damage to the model. The behavioural study found an effect of semantic but not phonological intervention. Through an explicit computational simulation, we therefore employed intervention data to evaluate our theoretical understanding of the processes underlying acquisition of lexical items for production and how they may vary in children with developmental language difficulties

The role of exercise training on lipoprotein profiles in adolescent males

BACKGROUND: Major cardiovascular disorders are being recognized earlier in life. In this study we examined the effects of swimming and soccer training on male adolescent lipid-lipoprotein profiles relative to a maturity matched control group to determine the effects of these exercises on specific cardiovascular risk and anti-risk factors. METHODS: Forty five adolescent males (11.81 ± 1.38 yr) including swimmers (SW), soccer players (SO), and non-athlete, physically active individuals as controls (C), participated in this study. Training groups completed 12-wk exercise programs on three non-consecutive days per week. Plasma low-density lipoprotein (LDL), very low density lipoprotein (VLDL), high density lipoprotein (HDL), apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), total cholesterol (TC), and triglyceride (TG) levels were measured in control, pre-training, during-training, and post-training. RESULTS: In response to the 12-wk training period, the SO group demonstrated a decrease in the mean LDL level compared to the SW and C (SW: 0.15%; SO: −9.51%; C: 19.59%; p < 0.001) groups. There was an increase in both the SW and SO groups vs. the control in mean HDL (SW: 5.66%; SO: 3.07%; C: −7.21%; p < 0.05) and apoA-I (SW: 3.86%; SO: 5.48%; C: −1.01%; p < 0.05). ApoB was considerably lower in the training groups vs. control (SW: −9.52%; SO: −13.87%; C: 21.09%; p < 0.05). ApoA-I/apoB ratio was significantly higher in training groups vs. control (SW: 16.74%; SO: 23.71%; C: −17.35%; p < 0.001). There were no significant differences between groups for other factors. CONCLUSIONS: The favorable alterations in LDL, HDL, apoA-I, and apoB observed in the training groups suggest that both regular swimming or soccer exercise can potentially mitigate cardiovascular risk in adolescent males

A Search for Variability in Exoplanet Analogues and Low-Gravity Brown Dwarfs

We report the results of a $J$-band survey for photometric variability in a sample of young, low-gravity objects using the New Technology Telescope (NTT) and the United Kingdom InfraRed Telescope (UKIRT). Surface gravity is a key parameter in the atmospheric properties of brown dwarfs and this is the first large survey that aims to test the gravity dependence of variability properties. We do a full analysis of the spectral signatures of youth and assess the group membership probability of each target using membership tools from the literature. This results in a 30 object sample of young low-gravity brown dwarfs. Since we are lacking in objects with spectral types later than L9, we focus our statistical analysis on the L0-L8.5 objects. We find that the variability occurrence rate of L0-L8.5 low-gravity brown dwarfs in this survey is $30^{+16}_{-8}\%$. We reanalyse the results of Radigan 2014 and find that the field dwarfs with spectral types L0-L8.5 have a variability occurrence rate of $11^{+13}_{-4}\%$. We determine a probability of $98\%$ that the samples are drawn from different distributions. This is the first quantitative indication that the low-gravity objects are more likely to be variable than the field dwarf population. Furthermore, we present follow-up $J_S$ and $K_S$ observations of the young, planetary-mass variable object PSO 318.5-22 over three consecutive nights. We find no evidence of phase shifts between the $J_S$ and $K_S$ bands and find higher $J_S$ amplitudes. We use the $J_S$ lightcurves to measure a rotational period of $8.45\pm0.05~$hr for PSO 318.5-22.Comment: accepted for publication in MNRA

PO2 Cycling Reduces Diaphragm Fatigue by Attenuating ROS Formation

Prolonged muscle exposure to low PO2 conditions may cause oxidative stress resulting in severe muscular injuries. We hypothesize that PO2 cycling preconditioning, which involves brief cycles of diaphragmatic muscle exposure to a low oxygen level (40 Torr) followed by a high oxygen level (550 Torr), can reduce intracellular reactive oxygen species (ROS) as well as attenuate muscle fatigue in mouse diaphragm under low PO2. Accordingly, dihydrofluorescein (a fluorescent probe) was used to monitor muscular ROS production in real time with confocal microscopy during a lower PO2 condition. In the control group with no PO2 cycling, intracellular ROS formation did not appear during the first 15 min of the low PO2 period. However, after 20 min of low PO2, ROS levels increased significantly by ∼30% compared to baseline, and this increase continued until the end of the 30 min low PO2 condition. Conversely, muscles treated with PO2 cycling showed a complete absence of enhanced fluorescence emission throughout the entire low PO2 period. Furthermore, PO2 cycling-treated diaphragm exhibited increased fatigue resistance during prolonged low PO2 period compared to control. Thus, our data suggest that PO2 cycling mitigates diaphragm fatigue during prolonged low PO2. Although the exact mechanism for this protection remains to be elucidated, it is likely that through limiting excessive ROS levels, PO2 cycling initiates ROS-related antioxidant defenses

Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses

The spread of SARS-CoV-2 and ongoing COVID-19 pandemic underscores the need for new treatments. Here we report that cannabidiol (CBD) inhibits infection of SARS-CoV-2 in cells and mice. CBD and its metabolite 7-OH-CBD, but not THC or other congeneric cannabinoids tested, potently block SARS-CoV-2 replication in lung epithelial cells. CBD acts after viral entry, inhibiting viral gene expression and reversing many effects of SARS-CoV-2 on host gene transcription. CBD inhibits SARS-CoV-2 replication in part by up-regulating the host IRE1alpha RNase endoplasmic reticulum (ER) stress response and interferon signaling pathways. In matched groups of human patients from the National COVID Cohort Collaborative, CBD (100 mg/ml oral solution per medical records) had a significant negative association with positive SARS-CoV-2 tests. This study highlights CBD as a potential preventative agent for early-stage SARS-CoV-2 infection and merits future clinical trials. We caution against use of non-medical formulations including edibles, inhalants or topicals as a preventative or treatment therapy at the present time

A near-infrared morphological comparison of high-redshift submm and radio galaxies: massive star-forming discs vs relaxed spheroids

We present deep, high-quality K-band images of complete subsamples of powerful radio and sub-mm galaxies at z=2. The data were obtained in the best available seeing at UKIRT and Gemini North, with integration times scaled to ensure that comparable rest-frame surface brightness levels are reached for all galaxies. We fit two-dimensional axi-symmetric galaxy models to determine galaxy morphologies at rest-frame optical wavelengths > 4000A, varying luminosity, axial ratio, half-light radius, and Sersic index. We find that, while some images show evidence of galaxy interactions, >95% of the rest-frame optical light in all galaxies is well-described by these simple models. We also find a clear difference in morphology between these two classes of galaxy; fits to the individual images and image stacks reveal that the radio galaxies are moderately large (=8.4+-1.1kpc; median r{1/2}=7.8), de Vaucouleurs spheroids ( = 4.07+-0.27; median n=3.87), while the sub-mm galaxies appear to be moderately compact (=3.4+-0.3kpc; median r{1/2}=3.1kpc) exponential discs (=1.44+-0.16; median n=1.08). We show that the z=2 radio galaxies display a well-defined Kormendy relation but that, while larger than other recently-studied high-z massive galaxy populations, they are still ~1.5 times smaller than their local counterparts. The scalelengths of the starlight in the sub-mm galaxies are comparable to those reported for the molecular gas. Their sizes are also similar to those of comparably massive quiescent galaxies at z>1.5. In terms of stellar mass surface density, the majority of the radio galaxies lie within the locus defined by local ellipticals. In contrast, while best modelled as discs, most of the sub-mm galaxies have higher stellar mass densities than local galaxies, and appear destined to evolve into present-day massive ellipticals.Comment: 24 pages, 9 figure

Frequency and Severity Approaches to Indexing Exposure to Trauma: The Critical Incident History Questionnaire for Police Officers

The Critical Incident History Questionnaire indexes cumulative exposure to traumatic incidents in police by examining incident frequency and rated severity. In over 700 officers, event severity was negatively correlated (rs = -61) with frequency of exposure. Cumulative exposure indices that varied emphasis on frequency and severity-using both nomothetic and idiographic methods-all showed satisfactory psychometric properties and similar correlates. All indices were only modestly related to posttraumatic stress disorder (PTSD) symptoms. Ratings of incident severity were not influenced by whether officers had ever experienced the incident. Because no index summarizing cumulative exposure to trauma had superior validity, our findings suggest that precision is not increased if frequency is weighted by severity