Evaluation of a portable retinal imaging device: towards a comparative quantitative analysis for morphological measurements of retinal blood vessels

This study investigated the possibility of using low-cost, handheld, retinal imaging devices for the automatic extraction of quantifiable measures of retinal blood vessels. Initially, the available handheld devices were compared using a Zeiss model eye incorporating a USAF resolution test chart to assess their optical properties. The only suitable camera of the five evaluated was the Horus DEC 200. This device was then subjected to a detailed evaluation in which images in human eyes taken from the handheld camera were compared in a quantitative analysis with those of the same eye from a Canon CR-DGi retinal desktop camera. We found that the Horus DEC 200 exhibited shortcomings in capturing images of human eyes by comparison with the Canon. More images were rejected as being unevaluable or suffering failures in automatic segmentation than with the Canon, and even after exclusion of affected images, the Horus yielded lower measurements of vessel density than the Canon. A number of issues affecting handheld cameras in general and some features of the Horus in particular have been identified that might contribute to the observed differences in performance. Some potential mitigations are discussed which might yield improvements in performance, thus potentially facilitating use of handheld retinal imaging devices for quantitative retinal microvascular measurements

Gene Essentiality Profiling Reveals Gene Networks and Synthetic Lethal Interactions with Oncogenic Ras

The genetic dependencies of human cancers widely vary. Here, we catalog this heterogeneity and use it to identify functional gene interactions and genotype-dependent liabilities in cancer. By using genome-wide CRISPR-based screens, we generate a gene essentiality dataset across 14 human acute myeloid leukemia (AML) cell lines. Sets of genes with correlated patterns of essentiality across the lines reveal new gene relationships, the essential substrates of enzymes, and the molecular functions of uncharacterized proteins. Comparisons of differentially essential genes between Ras-dependent and -independent lines uncover synthetic lethal partners of oncogenic Ras. Screens in both human AML and engineered mouse pro-B cells converge on a surprisingly small number of genes in the Ras processing and MAPK pathways and pinpoint PREX1 as an AML-specific activator of MAPK signaling. Our findings suggest general strategies for defining mammalian gene networks and synthetic lethal interactions by exploiting the natural genetic and epigenetic diversity of human cancer cells. Keywords: CRISPR; AML; synthetic lethality; gene networks; RAS; genetic screensNational Institutes of Health (U.S.) (Grant CA103866)National Institutes of Health (U.S.) (Grant F31CA189437

Five Millennia of Paleotemperature from Tree-Rings in the Great Basin, USA

The instrumental temperature record is of insufficient length to fully express the natural variability of past temperature. High elevation tree-ring widths from Great Basin bristlecone pine (Pinus longaeva) are a particularly useful proxy to infer temperatures prior to the instrumental record in that the tree-rings are annually dated and extend for millennia. From ring-width measurements integrated with past treeline elevation data we infer decadal- to millennial-scale temperature variability over the past 4,500 years for the Great Basin, USA. We find that twentieth century treeline advances are greater than in at least 4,000 years. There is also evidence for substantial volcanic forcing of climate in the preindustrial record and considerable covariation between high elevation tree-ring widths and temperature estimates from an atmosphere– ocean general circulation model over much of the last millennium. A long-term temperature decline of ~-1.1 °C since the mid-Holocene underlies substantial volcanic forcing of climate in the preindustrial record

TADPOL: A 1.3 mm Survey of Dust Polarization in Star-forming Cores and Regions

We present {\lambda}1.3 mm CARMA observations of dust polarization toward 30 star-forming cores and 8 star-forming regions from the TADPOL survey. We show maps of all sources, and compare the ~2.5" resolution TADPOL maps with ~20" resolution polarization maps from single-dish submillimeter telescopes. Here we do not attempt to interpret the detailed B-field morphology of each object. Rather, we use average B-field orientations to derive conclusions in a statistical sense from the ensemble of sources, bearing in mind that these average orientations can be quite uncertain. We discuss three main findings: (1) A subset of the sources have consistent magnetic field (B-field) orientations between large (~20") and small (~2.5") scales. Those same sources also tend to have higher fractional polarizations than the sources with inconsistent large-to-small-scale fields. We interpret this to mean that in at least some cases B-fields play a role in regulating the infall of material all the way down to the ~1000 AU scales of protostellar envelopes. (2) Outflows appear to be randomly aligned with B-fields; although, in sources with low polarization fractions there is a hint that outflows are preferentially perpendicular to small-scale B-fields, which suggests that in these sources the fields have been wrapped up by envelope rotation. (3) Finally, even at ~2.5" resolution we see the so-called "polarization hole" effect, where the fractional polarization drops significantly near the total intensity peak. All data are publicly available in the electronic edition of this article.Comment: 53 pages, 37 figures -- main body (13 pp., 3 figures), source maps (32 pp., 34 figures), source descriptions (8 pp.). Accepted by the Astrophysical Journal Supplemen

Community-based pre-pregnancy care programme improves pregnancy preparation in women with pregestational diabetes.

AIMS/HYPOTHESIS: Women with diabetes remain at increased risk of adverse pregnancy outcomes associated with poor pregnancy preparation. However, women with type 2 diabetes are less aware of and less likely to access pre-pregnancy care (PPC) compared with women with type 1 diabetes. We developed and evaluated a community-based PPC programme with the aim of improving pregnancy preparation in all women with pregestational diabetes. METHODS: This was a prospective cohort study comparing pregnancy preparation measures before and during/after the PPC intervention in women with pre-existing diabetes from 1 June 2013 to 28 February 2017. The setting was 422 primary care practices and ten National Health Service specialist antenatal diabetes clinics. A multifaceted approach was taken to engage women with diabetes and community healthcare teams. This included identifying and sending PPC information leaflets to all eligible women, electronic preconception care templates, online education modules and resources, and regional meetings and educational events. Key outcomes were preconception folic acid supplementation, maternal HbA1c level, use of potentially harmful medications at conception and gestational age at first presentation, before and during/after the PPC programme. RESULTS: A total of 306 (73%) primary care practices actively participated in the PPC programme. Primary care databases were used to identify 5075 women with diabetes aged 18-45 years. PPC leaflets were provided to 4558 (89.8%) eligible women. There were 842 consecutive pregnancies in women with diabetes: 502 before and 340 during/after the PPC intervention. During/after the PPC intervention, pregnant women with type 2 diabetes were more likely to achieve target HbA1c levels ≤48 mmol/mol (6.5%) (44.4% of women before vs 58.5% of women during/after PPC intervention; p = 0.016) and to take 5 mg folic acid daily (23.5% and 41.8%; p = 0.001). There was an almost threefold improvement in 'optimal' pregnancy preparation in women with type 2 diabetes (5.8% and 15.1%; p = 0.021). Women with type 1 diabetes presented for earlier antenatal care during/after PPC (54.0% vs 67.3% before 8 weeks' gestation; p = 0.003) with no other changes. CONCLUSIONS/INTERPRETATION: A pragmatic community-based PPC programme was associated with clinically relevant improvements in pregnancy preparation in women with type 2 diabetes. To our knowledge, this is the first community-based PPC intervention to improve pregnancy preparation for women with type 2 diabetes. DATA AVAILABILITY: Further details of the data collection methodology, individual clinic data and the full audit reports for healthcare professionals and service users are available from https://digital.nhs.uk/data-and-information/clinical-audits-and-registries/our-clinical-audits-and-registries/national-pregnancy-in-diabetes-audit

Cluster M Mycobacteriophages Bongo, PegLeg, and Rey with Unusually Large Repertoires of tRNA Isotopes

Genomic analysis of a large set of phages infecting the common hostMycobacterium smegmatis mc2155 shows that they span considerable genetic diversity. There are more than 20 distinct types that lack nucleotide similarity with each other, and there is considerable diversity within most of the groups. Three newly isolated temperate mycobacteriophages, Bongo, PegLeg, and Rey, constitute a new group (cluster M), with the closely related phages Bongo and PegLeg forming subcluster M1 and the more distantly related Rey forming subcluster M2. The cluster M mycobacteriophages have siphoviral morphologies with unusually long tails, are homoimmune, and have larger than average genomes (80.2 to 83.7 kbp). They exhibit a variety of features not previously described in other mycobacteriophages, including noncanonical genome architectures and several unusual sets of conserved repeated sequences suggesting novel regulatory systems for both transcription and translation. In addition to containing transfer-messenger RNA and RtcB-like RNA ligase genes, their genomes encode 21 to 24 tRNA genes encompassing complete or nearly complete sets of isotypes. We predict that these tRNAs are used in late lytic growth, likely compensating for the degradation or inadequacy of host tRNAs. They may represent a complete set of tRNAs necessary for late lytic growth, especially when taken together with the apparent lack of codons in the same late genes that correspond to tRNAs that the genomes of the phages do not obviously encode

Effect of Tilted Magnetic Field on the Anomalous H=0 Conducting Phase in High-Mobility Si MOSFETs

The suppression by a magnetic field of the anomalous H=0 conducting phase in high-mobility silicon MOSFETs is independent of the angle between the field and the plane of the 2D electron system. In the presence of a parallel field large enough to fully quench the anomalous conducting phase, the behavior is similar to that of disordered GaAs/AlGaAs heterostructures: the system is insulating in zero (perpendicular) field and exhibits reentrant insulator-quantum Hall effect-insulator transitions as a function of perpendicular field. The results demonstrate that the suppression of the low-T phase is related only to the electrons' spin.Comment: 4 pages, including 3 figures. We corrected several typos in the figures and caption