Biocatalytic Removal of Organic Sulfur from Coal

The objective is to characterize more completely the biochemical ability of the bacterium, Rhodococcus rhodochrous IGTS8, to cleave carbon-sulfur bonds with emphasis on data that will allow the development of a practical coal biodesulfurization process. Another approach for increasing the desulfurization activity of the IGTS8 cultures is to produce strains genetically that have higher activity. The goal of this part of research is to achieve strain improvement by introducing a stronger promoter using genetic engineering techniques. The promoter regulates the transcription of the genes for the desulfurization enzymes, and a stronger promoter, would up-regulate the expression of these genes, resulting in cells with higher desulfurization activity. Promoter probe vectors are used to identify and isolate promoters from a DNA library of the experimental organism. The major accomplishments have been to obtain high biodesulfurization activity in nonaqueous, media, especially using freeze-dried cells, and to have isolated strong promoters from R. rhodochrous IGTS8 which will be used to engineer the organism to produce strains with higher biocatalytic activity

Predicting optical coherence tomography-derived diabetic macular edema grades from fundus photographs using deep learning

Diabetic eye disease is one of the fastest growing causes of preventable blindness. With the advent of anti-VEGF (vascular endothelial growth factor) therapies, it has become increasingly important to detect center-involved diabetic macular edema (ci-DME). However, center-involved diabetic macular edema is diagnosed using optical coherence tomography (OCT), which is not generally available at screening sites because of cost and workflow constraints. Instead, screening programs rely on the detection of hard exudates in color fundus photographs as a proxy for DME, often resulting in high false positive or false negative calls. To improve the accuracy of DME screening, we trained a deep learning model to use color fundus photographs to predict ci-DME. Our model had an ROC-AUC of 0.89 (95% CI: 0.87-0.91), which corresponds to a sensitivity of 85% at a specificity of 80%. In comparison, three retinal specialists had similar sensitivities (82-85%), but only half the specificity (45-50%, p<0.001 for each comparison with model). The positive predictive value (PPV) of the model was 61% (95% CI: 56-66%), approximately double the 36-38% by the retinal specialists. In addition to predicting ci-DME, our model was able to detect the presence of intraretinal fluid with an AUC of 0.81 (95% CI: 0.81-0.86) and subretinal fluid with an AUC of 0.88 (95% CI: 0.85-0.91). The ability of deep learning algorithms to make clinically relevant predictions that generally require sophisticated 3D-imaging equipment from simple 2D images has broad relevance to many other applications in medical imaging

Mid-infrared selection of AGN

Since a large fraction of active galactic nuclei (AGN) is missed in common UV-excess surveys and is even hard to find in radio, near-IR and X-ray surveys, we have used a new AGN selection technique which is expected to be not affected by extinction. Within the scientific verification of the ISOCAM Parallel Survey at 6.7 micron we have discovered objects with exceptional mid-infrared (MIR) emission. They are essentially not detected on IRAS-ADDSCANs and only very few of them show up in the NVSS and FIRST radio surveys. Various colour criteria of the 6.7 micron data with 2MASS and optical wavebands show that the sources reach more extreme IR colours than the sources in the Hubble Deep Field-South and the ELAIS survey. The comparison with known object types suggests that we have found AGN with a pronounced MIR emission, probably due to circum-nuclear dust. First results from optical spectroscopy of ten candidates corroborate this interpretation showing four AGN, two reddened LINER and four extremely reddened emission-line galaxies with MIR/FIR flux ratios higher than for known pure starburst galaxies. The results will make a significant contribution to the debate on the entire AGN population.Comment: 4 pages, 2 figures, accepted for publication as Letter in Astronomy & Astrophysic

An Aromatic Inventory of the Local Volume

Using infrared photometry from the Spitzer Space Telescope, we perform the first inventory of aromatic feature emission (AFE, but also commonly referred to as PAH emission) for a statistically complete sample of star-forming galaxies in the local volume. The photometric methodology involved is calibrated and demonstrated to recover the aromatic fraction of the IRAC 8 micron flux with a standard deviation of 6% for a training set of 40 SINGS galaxies (ranging from stellar to dust dominated) with both suitable mid-infrared Spitzer IRS spectra and equivalent photometry. A potential factor of two improvement could be realized with suitable 5.5 and 10 micron photometry, such as what may be provided in the future by JWST. The resulting technique is then applied to mid-infrared photometry for the 258 galaxies from the Local Volume Legacy (LVL) survey, a large sample dominated in number by low-luminosity dwarf galaxies for which obtaining comparable mid-infrared spectroscopy is not feasible. We find the total LVL luminosity due to five strong aromatic features in the 8 micron complex to be 2.47E10 solar luminosities with a mean volume density of 8.8E6 solar luminosities per cubic Megaparsec. Twenty-four of the LVL galaxies, corresponding to a luminosity cut at M = -18.22 in the B band, account for 90% of the aromatic luminosity. Using oxygen abundances compiled from the literature for 129 of the 258 LVL galaxies, we find a correlation between metallicity and the aromatic to total infrared emission ratio but not the aromatic to total 8 micron dust emission ratio. A possible explanation is that metallicity plays a role in the abundance of aromatic molecules relative to the total dust content, but other factors such as star formation and/or the local radiation field affect the excitation of those molecules.Comment: ApJ in press; 29 pages, 14 figures, 3 tables; emulateapj forma

Magnetic resonance imaging pattern recognition in childhood bilateral basal ganglia disorders

Bilateral basal ganglia abnormalities on MRI are observed in a wide variety of childhood disorders. MRI pattern recognition can enable rationalization of investigations and also complement clinical and molecular findings, particularly confirming genomic findings and also enabling new gene discovery. A pattern recognition approach in children with bilateral basal ganglia abnormalities on brain MRI was undertaken in this international multicentre cohort study. Three hundred and five MRI scans belonging to 201 children with 34 different disorders were rated using a standard radiological scoring proforma. In addition, literature review on MRI patterns was undertaken in these 34 disorders and 59 additional disorders reported with bilateral basal ganglia MRI abnormalities. Cluster analysis on first MRI findings from the study cohort grouped them into four clusters: Cluster 1—T2-weighted hyperintensities in the putamen; Cluster 2—T2-weighted hyperintensities or increased MRI susceptibility in the globus pallidus; Cluster 3—T2-weighted hyperintensities in the globus pallidus, brainstem and cerebellum with diffusion restriction; Cluster 4—T1-weighted hyperintensities in the basal ganglia. The 34 diagnostic categories included in this study showed dominant clustering in one of the above four clusters. Inflammatory disorders grouped together in Cluster 1. Mitochondrial and other neurometabolic disorders were distributed across clusters 1, 2 and 3, according to lesions dominantly affecting the striatum (Cluster 1: glutaric aciduria type 1, propionic acidaemia, 3-methylglutaconic aciduria with deafness, encephalopathy and Leigh-like syndrome and thiamine responsive basal ganglia disease associated with SLC19A3), pallidum (Cluster 2: methylmalonic acidaemia, Kearns Sayre syndrome, pyruvate dehydrogenase complex deficiency and succinic semialdehyde dehydrogenase deficiency) or pallidum, brainstem and cerebellum (Cluster 3: vigabatrin toxicity, Krabbe disease). The Cluster 4 pattern was exemplified by distinct T1-weighted hyperintensities in the basal ganglia and other brain regions in genetically determined hypermanganesemia due to SLC39A14 and SLC30A10. Within the clusters, distinctive basal ganglia MRI patterns were noted in acquired disorders such as cerebral palsy due to hypoxic ischaemic encephalopathy in full-term babies, kernicterus and vigabatrin toxicity and in rare genetic disorders such as 3-methylglutaconic aciduria with deafness, encephalopathy and Leigh-like syndrome, thiamine responsive basal ganglia disease, pantothenate kinase-associated neurodegeneration, TUBB4A and hypermanganesemia. Integrated findings from the study cohort and literature review were used to propose a diagnostic algorithm to approach bilateral basal ganglia abnormalities on MRI. After integrating clinical summaries and MRI findings from the literature review, we developed a prototypic decision-making electronic tool to be tested using further cohorts and clinical practice

The census as an information source in public policy-making

This paper provides an assessment of the value of national population censuses as information sources with specific reference toUK census data and its use in policy-making. Mixed methods were adopted to collect quantitative and qualitative data from twosources: (1) a content analysis of policy documents, and (2) interviews with policy-makers in Scotland. The findings highlight thatalthough the general value of the census is recognised, policy-makers are not necessarily closely engaged with the census as a toolfor directing the development and implementation of policy. This is evident, for example in a lack of awareness of proposed changesto the census, and infrequent deployment of available data. The opportunity to change perceptions among policy-makers, and toexpand the application of census data in public policy, is identified. With a novel focus on the deployment of censuses as sources ofevidence for policy-making that includes the views of policy-makers from both within and beyond government, this workcontributes to an established body of global research on international censuses

Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination.

Abstract OBJECTIVE: We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination. METHODS: We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients. RESULTS: The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10\u2009mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of 652 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077). CONCLUSION: Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation