2,551 research outputs found

    The interstellar medium and feedback in the progenitors of the compact passive galaxies at z~2

    Get PDF
    Quenched galaxies at z>2 are nearly all very compact relative to z~0, suggesting a physical connection between high stellar density and efficient, rapid cessation of star-formation. We present restframe UV spectra of Lyman-break galaxies (LBGs) at z~3 selected to be candidate progenitors of quenched galaxies at z~2 based on their compact restframe optical sizes and high surface density of star-formation. We compare their UV properties to those of more extended LBGs of similar mass and star formation rate (non-candidates). We find that candidate progenitors have faster ISM gas velocities and higher equivalent widths of interstellar absorption lines, implying larger velocity spread among absorbing clouds. Candidates deviate from the relationship between equivalent widths of Lyman-alpha and interstellar absorption lines in that their Lyman-alpha emission remains strong despite high interstellar absorption, possibly indicating that the neutral HI fraction is patchy such that Lyman-alpha photons can escape. We detect stronger CIV P-Cygni features (emission and absorption) and HeII emission in candidates, indicative of larger populations of metal rich Wolf-Rayet stars compared to non-candidates. The faster bulk motions, broader spread of gas velocity, and Lyman-alpha properties of candidates are consistent with their ISM being subject to more energetic feedback than non-candidates. Together with their larger metallicity (implying more evolved star-formation activity) this leads us to propose, if speculatively, that they are likely to quench sooner than non-candidates, supporting the validity of selection criteria used to identify them as progenitors of z~2 passive galaxies. We propose that massive, compact galaxies undergo more rapid growth of stellar mass content, perhaps because the gas accretion mechanisms are different, and quench sooner than normally-sized LBGs at these early epochs.Comment: Accepted for publication in the Astrophysical Journa

    Novel, Anti-hTNF-α Variable New Antigen Receptor Formats with Enhanced Neutralising Potency and Multifunctionality, Generated for Therapeutic Development

    Get PDF
    ACKNOWLEDGMENTS The authors wish to acknowledge the funding support for this work from MSD/Scottish Universities Life Sciences Alliance (SULSA), Scottish Enterprise, the Biotechnology and Biological Sciences Research Council (BBSRC), and the University of Aberdeen. FUNDING Grateful for support from Biotechnology and Biological Sciences Research Council (BB/K010905/1), Scottish Enterprise [VNAR_001 (2012)], Scottish Universities Life Sciences Alliance/ MSD (MSD01_A_Porter-Teismann), and the College of Life Sciences and Medicine, University of Aberdeen (Fee bursary to OU).Peer reviewedPublisher PD

    Acceleration of infectious disease drug discovery and development using a humanized model of drug metabolism

    Get PDF
    A key step in drug discovery, common to many disease areas, is preclinical demonstration of efficacy in a mouse model of disease. However, this demonstration and its translation to the clinic can be impeded by mouse-specific pathways of drug metabolism. Here we show that a mouse line extensively humanized for the cytochrome P450 gene superfamily (“8HUM”) can circumvent these problems. The pharmacokinetics, metabolite profiles and magnitude of drug-drug interactions of a test set of approved medicines were in much closer alignment with clinical observations than in wild-type mice. Infection with Mycobacterium tuberculosis, Leishmania donovani and Trypanosoma cruzi was well tolerated in 8HUM, permitting efficacy assessment. During such assessments, mouse-specific metabolic liabilities were bypassed while the impact of clinically relevant active metabolites and DDI on efficacy were well-captured. Removal of species differences in metabolism by replacement of wild-type mice with 8HUM therefore reduces compound attrition while improving clinical translation, accelerating drug discovery

    Chest drain aerosol generation in COVID-19 and emission reduction using a simple anti-viral filter

    Get PDF
    Introduction: The COVID-19 pandemic has been characterised by significant in-hospital virus transmission and deaths among healthcare workers. Sources of in-hospital transmission are not fully understood, with special precautions currently reserved for procedures previously shown to generate aerosols (particles <5 μm). Pleural procedures are not currently considered AGPs (Aerosol Generating Procedures), reflecting a lack of data in this area. Methods: An underwater seal chest drain bottle (R54500, Rocket Medical UK) was set up inside a 60-litre plastic box and connected via an airtight conduit to a medical air supply. A multichannel particle counter (TSI Aerotrak 9310 Aerosol Monitor) was placed inside the box, allowing measurement of particle count/cubic foot (pc/ft3) within six channel sizes: 0.3–0.5, 0.5–1, 1–3, 3–5, 5–10 and >10 μm. Stabilised particle counts at 1, 3 and 5 L/min were compared by Wilcoxon signed rank test; p values were Bonferroni-adjusted. Measurements were repeated with a simple anti-viral filter, designed using repurposed materials by the study team, attached to the drain bottle. The pressure within the bottle was measured to assess any effect of the filter on bottle function. Results: Aerosol emissions increased with increasing air flow, with the largest increase observed in smaller particles (0.3–3 μm). Concentration of the smallest particles (0.3–0.5 μm) increased from background levels by 700, 1400 and 2500 pc/ft3 at 1, 3 and 5 L/min, respectively. However, dispersion of particles of all sizes was effectively prevented by use of the viral filter at all flow rates. Use of the filter was associated with a maximum pressure rise of 0.3 cm H2O after 24 hours of flow at 5 L/min, suggesting minimal impact on drain function. Conclusion: A bubbling chest drain is a source of aerosolised particles, but emission can be prevented using a simple anti-viral filter. These data should be considered when designing measures to reduce in-hospital spread of SARS-CoV-2

    JWST MIRI and NIRCam Unveil Previously Unseen Infrared Stellar Populations in NGC 6822

    Full text link
    NGC 6822 is a nearby (\sim490 kpc) non-interacting low-metallicity (0.2 Z_\odot) dwarf galaxy which hosts several prominent Hii regions, including sites of highly embedded active star formation. In this work, we present an imaging survey of NGC 6822 conducted with the NIRCam and MIRI instruments onboard JWST. We provide a description of the data reduction, source extraction, and stellar population identifications from combined near- and mid-infrared (IR) photometry. Our NIRCam observations reach seven magnitudes deeper than previous JHKs surveys of this galaxy, which were sensitive to just below the tip of the red giant branch (TRGB). These JWST observations thus reveal for the first time in the near-IR the red clump stellar population and extend nearly three magnitudes deeper. In the mid-IR, we observe roughly two magnitudes below the TRGB with the MIRI F770W and F1000W filters. With these improvements in sensitivity, we produce a catalogue of \sim900,000 point sources over an area of \sim 6.0 x 4.3 arcmin2. We present several NIRCam and MIRI colour-magnitude diagrams and discuss which colour combinations provide useful separations of various stellar populations to aid in future JWST observation planning. Finally, we find populations of carbon- and oxygen-rich asymptotic giant branch stars which will assist in improving our understanding of dust production in low-metallicity, early Universe analogue galaxies

    Methylphenidate and \u3ci\u3eMemory and Attention Adaptation Training\u3c/i\u3e for persistent cognitive symptoms after traumatic brain injury: a randomized, placebo-controlled trial

    Get PDF
    The purpose of this multicenter, prospective, randomized, placebo-controlled study was to evaluate and compare the efficacy of two cognitive rehabilitation interventions (Memory and Attention Adaptation Training (MAAT) and Attention Builders Training (ABT)), with and without pharmacologic enhancement (i.e., with methylphenidate (MPH) or placebo), for treating persistent cognitive problems after traumatic brain injury (TBI). Adults with a history of TBI at least four months prior to study enrollment with either objective cognitive deficits or subjective cognitive complaints were randomized to receive MPH or placebo and MAAT or ABT, yielding four treatment combinations: MAAT/MPH (N=17), ABT/MPH (N=19), MAAT/placebo (N=17), and ABT/placebo (N=18). Assessments were conducted pre-treatment (baseline) and after six weeks of treatment (post-treatment). Outcome measures included scores on neuropsychological measures and subjective rating scales. Statistical analyses used linear regression models to predict post-treatment scores for each outcome variable by treatment type, adjusting for relevant covariates. Statistically significant (p\u3c0.05) treatment-related improvements in cognitive functioning were found for word list learning (MAAT/placebo\u3eABT/placebo), nonverbal learning (MAAT/MPH\u3eMAAT/placebo and MAAT/MPH\u3eABT/MPH), and auditory working memory and divided attention (MAAT/MPH\u3eABT/MPH). These results suggest that combined treatment with metacognitive rehabilitation (MAAT) and pharmacotherapy (MPH) can improve aspects of attention, episodic and working memory, and executive functioning after TBI

    Methylphenidate and Memory and Attention Adaptation Training for persistent cognitive symptoms after traumatic brain injury: a randomized, placebo-controlled trial

    Get PDF
    The purpose of this multicenter, prospective, randomized, placebo-controlled study was to evaluate and compare the efficacy of two cognitive rehabilitation interventions (Memory and Attention Adaptation Training (MAAT) and Attention Builders Training (ABT)), with and without pharmacological enhancement (ie, with methylphenidate (MPH) or placebo), for treating persistent cognitive problems after traumatic brain injury (TBI). Adults with a history of TBI at least 4 months before study enrollment with either objective cognitive deficits or subjective cognitive complaints were randomized to receive MPH or placebo and MAAT or ABT, yielding four treatment combinations: MAAT/MPH (N=17), ABT/MPH (N=19), MAAT/placebo (N=17), and ABT/placebo (N=18). Assessments were conducted pre-treatment (baseline) and after 6 weeks of treatment (post treatment). Outcome measures included scores on neuropsychological measures and subjective rating scales. Statistical analyses used linear regression models to predict post-treatment scores for each outcome variable by treatment type, adjusting for relevant covariates. Statistically significant (PABT/placebo), nonverbal learning (MAAT/MPH>MAAT/placebo and MAAT/MPH>ABT/MPH), and auditory working memory and divided attention (MAAT/MPH>ABT/MPH). These results suggest that combined treatment with metacognitive rehabilitation (MAAT) and pharmacotherapy (MPH) can improve aspects of attention, episodic and working memory, and executive functioning after TBI

    Methylphenidate and \u3ci\u3eMemory and Attention Adaptation Training\u3c/i\u3e for persistent cognitive symptoms after traumatic brain injury: a randomized, placebo-controlled trial

    Get PDF
    The purpose of this multicenter, prospective, randomized, placebo-controlled study was to evaluate and compare the efficacy of two cognitive rehabilitation interventions (Memory and Attention Adaptation Training (MAAT) and Attention Builders Training (ABT)), with and without pharmacologic enhancement (i.e., with methylphenidate (MPH) or placebo), for treating persistent cognitive problems after traumatic brain injury (TBI). Adults with a history of TBI at least four months prior to study enrollment with either objective cognitive deficits or subjective cognitive complaints were randomized to receive MPH or placebo and MAAT or ABT, yielding four treatment combinations: MAAT/MPH (N=17), ABT/MPH (N=19), MAAT/placebo (N=17), and ABT/placebo (N=18). Assessments were conducted pre-treatment (baseline) and after six weeks of treatment (post-treatment). Outcome measures included scores on neuropsychological measures and subjective rating scales. Statistical analyses used linear regression models to predict post-treatment scores for each outcome variable by treatment type, adjusting for relevant covariates. Statistically significant (p\u3c0.05) treatment-related improvements in cognitive functioning were found for word list learning (MAAT/placebo\u3eABT/placebo), nonverbal learning (MAAT/MPH\u3eMAAT/placebo and MAAT/MPH\u3eABT/MPH), and auditory working memory and divided attention (MAAT/MPH\u3eABT/MPH). These results suggest that combined treatment with metacognitive rehabilitation (MAAT) and pharmacotherapy (MPH) can improve aspects of attention, episodic and working memory, and executive functioning after TBI
    corecore