Comparison of 5-year progression of retinitis pigmentosa involving the posterior pole among siblings by means of SD-OCT: a retrospective study

The blockchain technology promises to transform finance, money and evengovernments. However, analyses of blockchain applicability and robustness typicallyfocus on isolated systems whose actors contribute mainly by running the consensusalgorithm. Here, we highlight the importance of considering trustless platformswithin the broader ecosystem that includes social and communication networks. Asan example, we analyse the flash-crash observed on 21st June 2017 in the Ethereumplatform and show that a major phenomenon of social coordination led to acatastrophic cascade of events across several interconnected systems. We proposethe concept of “emergent centralisation” to describe situations where a single systembecomes critically important for the functioning of the whole ecosystem, and arguethat such situations are likely to become more and more frequent in interconnectedsocio-technical systems. We anticipate that the systemic approach we propose willhave implications for future assessments of trustless systems and call for the attentionof policy-makers on the fragility of our interconnected and rapidly changing world

Quantitative Phosphoproteomics of CXCL12 (SDF-1) Signaling

CXCL12 (SDF-1) is a chemokine that binds to and signals through the seven transmembrane receptor CXCR4. The CXCL12/CXCR4 signaling axis has been implicated in both cancer metastases and human immunodeficiency virus type 1 (HIV-1) infection and a more complete understanding of CXCL12/CXCR4 signaling pathways may support efforts to develop therapeutics for these diseases. Mass spectrometry-based phosphoproteomics has emerged as an important tool in studying signaling networks in an unbiased fashion. We employed stable isotope labeling with amino acids in cell culture (SILAC) quantitative phosphoproteomics to examine the CXCL12/CXCR4 signaling axis in the human lymphoblastic CEM cell line. We quantified 4,074 unique SILAC pairs from 1,673 proteins and 89 phosphopeptides were deemed CXCL12-responsive in biological replicates. Several well established CXCL12-responsive phosphosites such as AKT (pS473) and ERK2 (pY204) were confirmed in our study. We also validated two novel CXCL12-responsive phosphosites, stathmin (pS16) and AKT1S1 (pT246) by Western blot. Pathway analysis and comparisons with other phosphoproteomic datasets revealed that genes from CXCL12-responsive phosphosites are enriched for cellular pathways such as T cell activation, epidermal growth factor and mammalian target of rapamycin (mTOR) signaling, pathways which have previously been linked to CXCL12/CXCR4 signaling. Several of the novel CXCL12-responsive phosphoproteins from our study have also been implicated with cellular migration and HIV-1 infection, thus providing an attractive list of potential targets for the development of cancer metastasis and HIV-1 therapeutics and for furthering our understanding of chemokine signaling regulation by reversible phosphorylation

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Enhancement-procedure outcomes in patients implanted with the Precisight multicomponent intraocular lens

Harvey S Uy,1,2 Carolina Tesone-Coelho,3 Harilaos Ginis4 1Peregrine Eye and Laser Institute, Makati, Philippines; 2Department of Ophthalmology and Visual Sciences, University of the Philippines, Manila, Philippines; 3Department of Research and Development, InfiniteVision Optics, Strasbourg, France; 4Research Department, Athens Eye Hospital, Athens, Greece Purpose: Eyes that have undergone phacoemulsification with implantation of a multicomponent intraocular lens (MCIOL) may further undergo an enhancement procedure for correction of residual refractive errors. The enhancement procedure is accomplished by exchanging the front lens used in the primary surgery with another lens containing the correct dioptric power. We evaluated the efficacy and safety of enhancement procedures among eyes that received an MCIOL.Methods: A total of 25 eyes that had undergone phacoemulsification with implantation of an MCIOL were found to have a residual error of refraction (spherical equivalent ≥0.75 D) 3 months after primary cataract surgery, and underwent further enhancement surgery. The main study outcomes were uncorrected and corrected distance visual acuity, subjective refraction, anterior-chamber depth, pachymetry, and endothelial cell count.Results: There was a statistically significant improvement in uncorrected distance visual acuity of approximately two lines after enhancement surgery (0.20±0.20–0.02±0.08 logMAR, P<0.001) and a significant decrease in residual spherical equivalent from 1.3±1.1 D to 0±0.38 D (P<0.001). There were no statistically significant changes in pre- and postenhancement corrected distance visual acuity, anterior-chamber depth, pachymetry, or keratometry. There was a statistically significant decrease (2.6%) in endothelial cell count (P<0.01), which could have been endothelial equilibration from the primary procedure. All enhancement surgeries were uneventful, and no major complications were observed.Conclusion: The MCIOL-enhancement procedure demonstrates statistical and clinical improvement in uncorrected distance visual acuity and correction of postoperative refractive errors. The Precisight IOL may be a useful choice for patients with high risk of having significant residual refractive errors after primary cataract surgery. Keywords: residual refractive error, cataract, piggyback lens, multicomponent intraocular lens, intraocular lens exchange, pseudophakic emmetropi