Near real time confocal microscopy of Ex Vivo cervical tissue: detection of dysplasia

textRecent studies have shown the ability of confocal microscopy to noninvasively image cells in vivo in real time. This ability to visualize nuclei in vivo shows the potential of confocal microscopy to dramatically improve the prevention, detection and therapy of epithelial cancers. More exciting is the potential to quantitatively measure nuclear morphometry providing a basis to automate the cancer detection process. This dissertation describes studies exploring this potential in ex vivo cervical tissue using acetic acid as a nuclear contrast agent. First the use of acetic acid was demonstrated to improved contrast in confocal images of cervical tissue sufficiently to allow segmentation. Segmentation is robust throughout the epithelium in most normal tissue and upper portions of tissue diagnosed with severe dysplasia. Based upon this segmentation, quantitative feature measurements were extracted from confocal images of cervical tissue in a pilot study to determine if the features would aide in the detection of dysplasia. Simultaneously, a qualitative review of confocal images was performed by untrained reviewers and compared with clinical colposcopic impressions, the standard clinical tool aiding in dysplasia detection. The sensitivity and specificity of both the qualitative (95% and 69%) and quantitative (100% and 91%) review were improved compared to colposcopic review (91% and 62%). Finally the ability of confocal microscopy to produce 3D images was explored as a further means to improve dysplasia detection. Based upon Beer’s equation for light attenuation, the scattering coefficient was extracted from 3D image sets of ex vivo cervical tissue and compared with histology from the same precancerous lesion. The results suggested a possible correlation between high scattering values and the presence of dysplasia. Quantitative 3D features were also extracted from 3D image sets and correlated with the presence of CIN 2/3. Increased separation between normal and CIN 2/3 biopsies was produced using the 3D features as compared to the 2D. More importantly, when additional information (scattering coefficient) is combined with the 2D features, the ability to distinguish between normal and CIN 2/3 is 100% accurate in this small sample set.Electrical and Computer Engineerin

Corrigendum to "Overview: oxidant and particle photochemical processes above a south-east Asian tropical rainforest (the OP3 project): introduction, rationale, location characteristics and tools" published in Atmos. Chem. Phys., 10, 169–199, 2010

Author(s): Hewitt, CN; Lee, JD; MacKenzie, AR; Barkley, MP; Carslaw, N; Carver, GD; Chappell, NA; Coe, H; Collier, C; Commane, R; Davies, F; Davison, B; DiCarlo, P; Di Marco, CF; Dorsey, JR; Edwards, PM; Evans, MJ; Fowler, D; Furneaux, KL; Gallagher, M; Guenther, A; Heard, DE; Helfter, C; Hopkins, J; Ingham, T; Irwin, M; Jones, C; Karunaharan, A; Langford, B; Lewis, AC; Lim, SF; MacDonald, SM; Mahajan, AS; Malpass, S; McFiggans, G; Mills, G; Misztal, P; Moller, S; Monks, PS; Nemitz, E; Nicolas-Perea, V; Oetjen, H; Oram, DE; Palmer, PI; Phillips, GJ; Pike, R; Plane, JMC; Pugh, T; Pyle, JA; Reeves, CE; Robinson, NH; Stewart, D; Stone, D; Whalley, LK; Yang,

A Roadmap for HEP Software and Computing R&D for the 2020s

Particle physics has an ambitious and broad experimental programme for the coming decades. This programme requires large investments in detector hardware, either to build new facilities and experiments, or to upgrade existing ones. Similarly, it requires commensurate investment in the R&D of software to acquire, manage, process, and analyse the shear amounts of data to be recorded. In planning for the HL-LHC in particular, it is critical that all of the collaborating stakeholders agree on the software goals and priorities, and that the efforts complement each other. In this spirit, this white paper describes the R&D activities required to prepare for this software upgrade.Peer reviewe

International genome-wide meta-analysis identifies new primary biliary cirrhosis risk loci and targetable pathogenic pathways.

Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery data sets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4,261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5 × 10(-8)) and used pathway analysis to identify JAK-STAT/IL12/IL27 signalling and cytokine-cytokine pathways, for which relevant therapies exist

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead