Black Carbon Contribution to the Aerosol Phase and its Scavenged Fraction in Mixed Phase Clouds at the High Alpine Site Jungfraujoch (3580m asl)

The mass fraction of black carbon (BC) in the atmospheric aerosol and its mixing state are important for the direct aerosol climate effect. These properties also determine if BC is incorporated into cloud hydrometeors (i.e. droplets and ice crystals) and are important because the microphysical and optical properties of the cloud are altered (indirect aerosol effect). Measurements were performed during several Cloud and Aerosol Characterization Experiments, in winter 2004 (CLACE3), summer 2004 (CLACE3.5), winter 2005 (CLACE4) and summer 2005 (CLACE4.5) at the high Alpine research station Jungfraujoch (3580 m asl)

Identification of a selective G1-phase benzimidazolone inhibitor by a senescence-targeted virtual screen using artificial neural networks

Cellular senescence is a barrier to tumorigenesis in normal cells and tumour cells undergo senescence responses to genotoxic stimuli, which is a potential target phenotype for cancer therapy. However, in this setting, mixed-mode responses are common with apoptosis the dominant effect. Hence, more selective senescence inducers are required. Here we report a machine learning-based in silico screen to identify potential senescence agonists. We built profiles of differentially affected biological process networks from expression data obtained under induced telomere dysfunction conditions in colorectal cancer cells and matched these to a panel of 17 protein targets with confirmatory screening data in PubChem. We trained a neural network using 3517 compounds identified as active or inactive against these targets. The resulting classification model was used to screen a virtual library of ~2M lead-like compounds. 147 virtual hits were acquired for validation in growth inhibition and senescence-associated β-galactosidase (SA-β-gal) assays. Among the found hits a benzimidazolone compound, CB-20903630, had low micromolar IC50 for growth inhibition of HCT116 cells and selectively induced SA-β-gal activity in the entire treated cell population without cytotoxicity or apoptosis induction. Growth suppression was mediated by G1 blockade involving increased p21 expression and suppressed cyclin B1, CDK1 and CDC25C. Additionally, the compound inhibited growth of multicellular spheroids and caused severe retardation of population kinetics in long term treatments. Preliminary structure-activity and structure clustering analyses are reported and expression analysis of CB-20903630 against other cell cycle suppressor compounds suggested a PI3K/AKT-inhibitor-like profile in normal cells, with different pathways affected in cancer cells

Vegetation and environmental patterns on soils derived from Hawkesbury Sandstone and Narrabeen substrata in Ku-ring-gai Chase National Park, New South Wales

[Abstract]: The vegetation patterns in the Central Coast region of New South Wales have been extensively studied with respect to single environmental variables, particularly soil nutrients. However, few data are available on the effects of multiple environmental variables. This study examines the relationships between vegetation and multiple environmental variables in natural vegetation on two underlying rock types, Hawkesbury sandstone and Narrabeen group shales and sandstones, in Ku-ring-gai Chase National Park, Sydney. Floristic composition and 17 environmental factors were characterized using duplicate 500 m2 quadrats from fifty sites representing a wide range of vegetation types. The patterns in vegetation and environmental factors were examined through multivariate analyses: indicator species analysis was used to provide an objective classification of plant community types, and the relationships between vegetation and environmental factors within the two soil types were examined through indirect and direct gradient analyses. Eleven plant communities were identified, which showed strong agreement with previous studies. The measured environmental factors showed strong correlations with vegetation patterns: within both soil types, the measured environmental variables explained approximately 32 - 35% of the variation in vegetation. No single measured environmental variable adequately described the observed gradients in vegetation; rather, vegetation gradients showed strong correlations with complex environmental gradients. These complex environmental gradients included nutrient, moisture and soil physical and site variables. These results suggest a simple 'nutrient' hypothesis regarding vegetation patterns in the Central Coast region is inadequate to explain variation in vegetation within soil types

Airborne Bacterial and Eukaryotic Community Structure across the United Kingdom Revealed by High-Throughput Sequencing

Primary biological aerosols often include allergenic and pathogenic microorganisms posing potential risks to human health. Moreover, there are airborne plant and animal pathogens that may have ecological and economic impact. In this study, we used high-throughput sequencing techniques (Illumina, MiSeq) targeting the 16S rRNA genes of bacteria and the 18S rRNA genes of eukaryotes, to characterize airborne primary biological aerosols. We used a filtration system on the UK Facility for Airborne Atmospheric Measurements (FAAM) research aircraft to sample a range of primary biological aerosols across southern England overflying surface measurement sites from Chilbolton to Weybourne. We identified 30 to 60 bacterial operational taxonomic units (OTUs) and 108 to 224 eukaryotic OTUs per sample. Moreover, 16S rRNA gene sequencing identified significant numbers of genera that have not been found in atmospheric samples previously or only been described in limited number of atmospheric field studies, which are rather old or published in local journals. This includes the genera Gordonia, Lautropia, and Psychroglaciecola. Some of the bacterial genera found in this study include potential human pathogens, for example, Gordonia, Sphingomonas, Chryseobacterium, Morganella, Fusobacterium, and Streptococcus. 18S rRNA gene sequencing showed Cladosporium to be the major genus in all of the samples, which is a well-known allergen and often found in the atmosphere. There were also genetic signatures of potentially allergenic taxa; for example, Pleosporales, Phoma, and Brassicales. Although there was no significant clustering of bacterial and eukaryotic communities depending on the sampling location, we found meteorological factors explaining significant variations in the community composition. The findings in this study support the application of DNA-based sequencing technologies for atmospheric science studies in combination with complementary spectroscopic and microscopic techniques for improved identification of primary biological aerosols

Controlled interventions to reduce burnout in physicians a systematic review and meta-analysis

IMPORTANCE Burnout is prevalent in physicians and can have a negative influence on performance, career continuation, and patient care. Existing evidence does not allow clear recommendations for the management of burnout in physicians. OBJECTIVE To evaluate the effectiveness of interventions to reduce burnout in physicians and whether different types of interventions (physician-directed or organization-directed interventions), physician characteristics (length of experience), and health care setting characteristics (primary or secondary care) were associated with improved effects. DATA SOURCES MEDLINE, Embase, PsycINFO, CINAHL, and Cochrane Register of Controlled Trials were searched from inception to May 31, 2016. The reference lists of eligible studies and other relevant systematic reviews were hand searched. STUDY SELECTION Randomized clinical trials and controlled before-after studies of interventions targeting burnout in physicians. DATA EXTRACTION AND SYNTHESIS Two independent reviewers extracted data and assessed the risk of bias. The main meta-analysis was followed by a number of prespecified subgroup and sensitivity analyses. All analyses were performed using random-effects models and heterogeneity was quantified. MAIN OUTCOMES AND MEASURES The core outcomewas burnout scores focused on emotional exhaustion, reported as standardized mean differences and their 95confidence intervals. RESULTS Twenty independent comparisons from 19 studieswere included in the meta-analysis (n = 1550 physicians; mean SD age, 40.3 9.5 years; 49%male). Interventionswere associated with small significant reductions in burnout (standardized mean difference SMD = ?0.29; 95%CI, ?0.42 to ?0.16; equal to a drop of 3 points on the emotional exhaustion domain of the Maslach Burnout Inventory above change in the controls). Subgroup analyses suggested significantly improved effects for organization-directed interventions (SMD = ?0.45; 95%CI, ?0.62 to ?0.28) compared with physician-directed interventions (SMD = ?0.18; 95%CI, ?0.32 to ?0.03). Interventions delivered in experienced physicians and in primary care were associated with higher effects compared with interventions delivered in inexperienced physicians and in secondary care, but these differences were not significant. The results were not influenced by the risk of bias ratings. CONCLUSIONS AND RELEVANCE Evidence from this meta-analysis suggests that recent intervention programs for burnout in physicians were associated with small benefits that may be boosted by adoption of organization-directed approaches. This finding provides support for the view that burnout is a problem of the whole health care organization, rather than individuals

A New Outlook on Ice Cloud through Sub-Millimetre-Wave Scattering

Scattering by atmospheric ice at sub-mm-wave frequencies is a challenge to both the cloud physics and light scattering communities owing to scattering at these frequencies being dependent on assumptions about the particle size distribution, ice crystal shape, orientation and size. Moreover, the scattering also depends on how the particle density is assumed to evolve with size. As there is as yet no prediction of a universal PSD or mass–dimension or density–dimension relationship, the modelling of ice crystals, so as to conserve the observed scattering and ice mass, is potentially problematic. In this presentation, the challenge presented by sub-mm-wave scattering is explored through the study of an ice cloud case using a new sub-mm spectral-like radiometer that was deployed on board an aircraft. Here, we evaluate the predictive quality of applying members from an ensemble model of cirrus ice crystals to modelling observed sub-millimetre brightness temperatures. The airborne straight and level near-nadir observations used here were from a case of ice cloud, which occurred during a winter period. The airborne microwave observations were obtained using the International Submillimetre Airborne Radiometer (ISMAR) [1], as the observations collected were at near-nadir we do not as yet consider polarisation. The ISMAR instrument has five central frequencies located between 118 and 664 GHz, with a number of sub-channels situated around some of the central frequencies to obtain spectral-like observations. The frequency selected for presentation is the 664 GHz “window” channel. This channel selection reduces uncertainties in modelling the gaseous spectroscopy, thereby enabling the scattering properties of members of the ensemble model to be more directly evaluated at this frequency. This is also the frequency that is most sensitive to assumptions about the ice crystal models and microphysics. The methodologies adopted for the calculation of the single-scattering properties of the ensemble model members at this frequency have been previously peer-reviewed and published [2, 3]. As such, this presentation concentrates on the application of these methodologies to the interpretation of the airborne ISMAR observations using a fast, state-of-the-art line-by-line radiative transfer model [4]. Moreover, state-of-the-art airborne observations of particle size distributions (PSDs) were also collected from the ice cloud case. These in-situ PSDs, as well as an often used database of in-situ PSDs collected during the SPARTICUS campaign in 2010, are applied to the two most compact and spatial hexagonal ice aggregate members of the ensemble model. A further ice aggregate model, called the Voronoi model, forming a chain of polyhedral particles, constructed to follow an observed density–dimension relationship, was also applied so as to simulate the observations. From the in-situ PSDs, geometric optics-based power law relationships have been previously obtained between the ice water content and the bulk extinction coefficient [5]. These same geometric optics-based relationships were estimated using the area–dimension power laws predicted by the ensemble model members and the Voronoi model. The best-fit ensemble model members to the observed power laws, and the Voronoi model, were applied in order to simulate the sub-mm-wave observations. Thus, we demonstrate consistency of model application from the limit of geometric optics (i.e. typically at visible wavelengths) to the sub-mm. In this presentation, we demonstrate a general overlap between the uncertainty in the radiative transfer simulations assuming the ensemble model members and the uncertainty in ISMAR brightness temperature observations at 664 GHz. However, portions of the straight and level runs were either simulated well with the compact aggregate model member or a three-component model, consisting of the two members of the ensemble model and the Voronoi particle, but never with one and the same model. Owing to the Voronoi model being the most spatial of all the models, this model simulated, to within the upper end of the experimental uncertainty, the ISMAR observations, but never the coldest observations at the highest sub-mm-wave frequency. However, if a different density–dimension relationship were to be adopted in the modelling of the Voronoi model that predicted higher mass values, then this should result in an improved agreement with the observations. It is as yet unclear as to which density–dimension relation is best to apply in general. These observations indicate changes in microphysics in terms of the mass–dimension profile and/or the size of the ice crystals and, therefore, represent a challenge to the global retrieval of ice cloud properties using the Ice Cloud Imager (ICI), which is due for launch around 2022. A further uncertainty is the assumed parametrised shape of the PSD. We also show in this presentation that the choice of PSD and ice crystal models are of equal importance in interpreting sub-mm-wave observations. [1] Fox, S et al., 2017: ISMAR: an airborne submillimetre radiometer. Atmos. Meas. Tech., doi:10.5194/ amt-10-477-2017. [2] Baran, A. J., et al., 2018: The applicability of physical optics in the millimetre and sub-millimetre spectral region. Part II: Application to a three-component model of ice cloud and its evaluation against the bulk single-scattering properties of various other aggregate models. JQSRT. 206, 68-80. [3] Baran, A. J., Hesse E., and Sourdeval O., 2017: The applicability of physical optics in the millimetre and sub-millimetre spectral region. Part I: The ray tracing with diffraction on facets method. JQSRT. 190, 83-100. [4] Havemann, S et al., The Havemann-Taylor Fast Radiative Transfer Code (HT-FRTC): a multipurpose code based on Principal Components, submitted to JQSRT (February 2018). [5] Fox, S et al., 2017: ISMAR: an airborne submillimetre radiometer. Atmos. Meas. Tech., doi:10.5194/ amt-10-477-2017.Peer reviewe

Management of multimorbidity using a patient-centred care model:a pragmatic cluster-randomised trial of the 3D approach

Background: The management of people with multiple chronic conditions challenges health-care systems designed around single conditions. There is international consensus that care for multimorbidity should be patient-centred, focus on quality of life, and promote self-management towards agreed goals. However, there is little evidence about the effectiveness of this approach. Our hypothesis was that the patient-centred, so-called 3D approach (based on dimensions of health, depression, and drugs) for patients with multimorbidity would improve their health-related quality of life, which is the ultimate aim of the 3D intervention. Methods: We did this pragmatic cluster-randomised trial in general practices in England and Scotland. Practices were randomly allocated to continue usual care (17 practices) or to provide 6-monthly comprehensive 3D reviews, incorporating patient-centred strategies that reflected international consensus on best care (16 practices). Randomisation was computer-generated, stratified by area, and minimised by practice deprivation and list size. Adults with three or more chronic conditions were recruited. The primary outcome was quality of life (assessed with EQ-5D-5L) after 15 months' follow-up. Participants were not masked to group assignment, but analysis of outcomes was blinded. We analysed the primary outcome in the intention-to-treat population, with missing data being multiply imputed. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN06180958. Findings: Between May 20, 2015, and Dec 31, 2015, we recruited 1546 patients from 33 practices and randomly assigned them to receive the intervention (n=797) or usual care (n=749). In our intention-to-treat analysis, there was no difference between trial groups in the primary outcome of quality of life (adjusted difference in mean EQ-5D-5L 0·00, 95% CI −0·02 to 0·02; p=0·93). 78 patients died, and the deaths were not considered as related to the intervention. Interpretation: To our knowledge, this trial is the largest investigation of the international consensus about optimal management of multimorbidity. The 3D intervention did not improve patients' quality of life. Funding: National Institute for Health Research

The Commensal Real-time ASKAP Fast Transients (CRAFT) survey

We are developing a purely commensal survey experiment for fast (<5s) transient radio sources. Short-timescale transients are associated with the most energetic and brightest single events in the Universe. Our objective is to cover the enormous volume of transients parameter space made available by ASKAP, with an unprecedented combination of sensitivity and field of view. Fast timescale transients open new vistas on the physics of high brightness temperature emission, extreme states of matter and the physics of strong gravitational fields. In addition, the detection of extragalactic objects affords us an entirely new and extremely sensitive probe on the huge reservoir of baryons present in the IGM. We outline here our approach to the considerable challenge involved in detecting fast transients, particularly the development of hardware fast enough to dedisperse and search the ASKAP data stream at or near real-time rates. Through CRAFT, ASKAP will provide the testbed of many of the key technologies and survey modes proposed for high time resolution science with the SKA.Comment: accepted for publication in PAS