A Review of Structural and Biomechanical Changes in the Cornea in Aging, Disease, and Photochemical Crosslinking

The study of corneal biomechanics is motivated by the tight relationship between biomechanical properties and visual function within the ocular system. For instance, variation in collagen fibril alignment and non-enzymatic crosslinks rank high among structural factors which give rise to the cornea's particular shape and ability to properly focus light. Gradation in these and other factors engender biomechanical changes which can be quantified by a wide variety of techniques. This review summarizes what is known about both the changes in corneal structure and associated changes in corneal biomechanical properties in aging, keratoconic, and photochemically crosslinked corneas. In addition, methods for measuring corneal biomechanics are discussed and the topics are related to both clinical studies and biomechanical modeling simulations

Toxicity and bioaccumulation of TNT in marine fish in sediment exposures

The bioaccumulation potential and toxicity of 2, 4, 6-trinitrotoluene (TNT) spiked to sediment was evaluated in juvenile sheeps head minnows (JSHM, Cyprinodon variegatus) and adult freckled blennies (FB, Hypsoblennius ionthas). The JSHM were exposed for 4 days in the presence or absence of a mesh separating fish from sediment. FB were exposed to sediment for 7 days. During the 24-day storage period(4 °C), extensive transformation of spiked TNT occurred and concentrations are expressed as the sum of TNT, aminodinitrotoluenes and diaminonitrotoluenes (Sum TNT), on a dry weight basis. Sum TNT in the overlying water, not exchanged during exposure, increased gradually. Survival was high( ≥ 90%) for JSHM exposed to 7 mgkg-1 and FB exposed to up to 260 mgkg-1. All SHM died after 24-h exposure to 340 mgkg-1. Isolation from sediment did not significantly affect water concentrations or decrease bioaccumulation. Uptake from contact to sediment was likely negligible and bioaccumulation was from the overlying water. The feeding rate of FB exposed to 1700 μmol kg-1 sediment suspended in water for 24-h was significantly reduced by 50%

XMM-Newton and Optical Observations of Cataclysmic Variables from SDSS

We report on XMM-Newton and optical results for 6 cataclysmic variables that were selected from Sloan Digital Sky Survey spectra because they showed strong HeII emission lines, indicative of being candidates for containing white dwarfs with strong magnetic fields. While high X-ray background rates prevented optimum results, we are able to confirm SDSSJ233325.92+152222.1 as an intermediate polar from its strong pulse signature at 21 min and its obscured hard X-ray spectrum. Ground-based circular polarization and photometric observations were also able to confirm SDSSJ142256.31-022108.1 as a polar with a period near 4 hr. Photometry of SDSSJ083751.00+383012.5 and SDSSJ093214.82+495054.7 solidifies the orbital period of the former as 3.18 hrs and confirms the latter as a high inclination system with deep eclipses.Comment: 31 pages, 14 figures. Accepted for publication in the Astronomical Journa

Wittgenstein's Thought Experiments and Relativity Theory

In this paper, I discuss the similarity between Wittgenstein’s use of thought experiments and Relativity Theory. I begin with introducing Wittgenstein’s idea of “thought experiments” and a tentative classification of different kinds of thought experiments in Wittgenstein’s work. Then, after presenting a short recap of some remarks on the analogy between Wittgenstein’s point of view and Einstein’s, I suggest three analogies between the status of Wittgenstein’s mental experiments and Relativity theory: the topics of time dilation, the search for invariants, and the role of measuring tools in Special Relativity. This last point will help to better define Wittgenstein’s idea of description as the core of his philosophical enterprise

Endovascular thrombectomy in patients with large core ischemic stroke: a cost-effectiveness analysis from the SELECT study

Background It is unknown whether endovascular thrombectomy (EVT) is cost effective in large ischemic core infarcts. Methods In the prospective, multicenter, cohort study of imaging selection study (SELECT), large core was defined as computed tomography (CT) ASPECTS(CTP) ischemic core volume (rCBF Results From 361 patients enrolled in SELECT, 105 had large core on CT or CTP (EVT 62, MM 43). 19 (31%) EVT vs 6 (14%) MM patients achieved modified Rankin Scale (mRS) score 0–2 (OR 3.27, 95% CI 1.11 to 9.62, P=0.03) with a shift towards better mRS (cOR 2.12, 95% CI 1.05 to 4.31, P=0.04). Over the projected lifetime of patients presenting with large core, EVT led to incremental costs of $33 094 and a gain of 1.34 QALYs per patient, resulting in ICER of$24 665 per QALY. EVT has a higher NMB compared with MM at lower (EVT -$42 747, MM -$76 740) and upper (EVT $155 041, MM$57 134) WTP thresholds. PSA confirmed the results and CEAC showed 77% and 92% acceptability of EVT at the WTP of $50 000 and$100 000, respectively. EVT was associated with an increment of $29 225 in societal costs. The pivotal EVT trials (HERMES, DAWN, DEFUSE 3) were dominant in a sensitivity analysis at the same inputs, with societal cost-savings of$37 901, $86 164 and$22 501 and a gain of 1.62, 2.36 and 2.21 QALYs, respectively. Conclusions In a non-randomized prospective cohort study, EVT resulted in better outcomes in large core patients with higher QALYs, NMB and high cost-effectiveness acceptability rates at current WTP thresholds. Randomized trials are needed to confirm these results. Clinical trial registration NCT0244658

Publishing and sharing multi-dimensional image data with OMERO

Imaging data are used in the life and biomedical sciences to measure the molecular and structural composition and dynamics of cells, tissues, and organisms. Datasets range in size from megabytes to terabytes and usually contain a combination of binary pixel data and metadata that describe the acquisition process and any derived results. The OMERO image data management platform allows users to securely share image datasets according to specific permissions levels: data can be held privately, shared with a set of colleagues, or made available via a public URL. Users control access by assigning data to specific Groups with defined membership and access rights. OMERO’s Permission system supports simple data sharing in a lab, collaborative data analysis, and even teaching environments. OMERO software is open source and released by the OME Consortium at www.openmicroscopy.org

Quantum Mechanical and Experimental Validation that Cyclobis(paraquat-p-phenylene) Forms a 1:1 Inclusion Complex with Tetrathiafulvalene

The promiscuous encapsulation of π-electron-rich guests by the π-electron-deficient host, cyclobis(paraquat-p-phenylene) (CBPQT^(4+)), involves the formation of 1:1 inclusion complexes. One of the most intensely investigated charge-transfer (CT) bands, assumed to result from inclusion of a guest molecule inside the cavity of CBPQT^(4+), is an emerald-green band associated with the complexation of tetrathiafulvalene (TTF) and its derivatives. This interpretation was called into question recently in this journal based on theoretical gas-phase calculations that reinterpreted this CT band in terms of an intermolecular side-on interaction of TTF with one of the bipyridinium (BIPY^(2+)) units of CBPQT^(4+), rather than the encapsulation of TTF inside the cavity of CBPQT^(4+). We carried out DFT calculations, including solvation, that reveal conclusively that the CT band emerging upon mixing TTF with CBPQT^(4+) arises from the formation of a 1:1 inclusion complex. In support of this conclusion, we have performed additional experiments on a [2]rotaxane in which a TTF unit, located in the middle of its short dumbbell, is prevented sterically from interacting with either one of the two BIPY^(2+) units of a CBPQT^(4+) ring residing on a separate [2]rotaxane in a side-on fashion. This [2]rotaxane has similar UV/Vis and ^1H NMR spectroscopic properties with those of 1:1 inclusion complexes of TTF and its derivatives with CBPQT^(4+). The [2]rotaxane exists as an equimolar mixture of cis- and trans-isomers associated with the disubstituted TTF unit in its dumbbell component. Solid-state structures were obtained for both isomers, validating the conclusion that the TTF unit, which gives rise to the CT band, resides inside CBPQT^(4+)

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Metadata management for high content screening in OMERO

High content screening (HCS) experiments create a classic data management challenge—multiple, large sets of heterogeneous structured and unstructured data, that must be integrated and linked to produce a set of “final” results. These different data include images, reagents, protocols, analytic output, and phenotypes, all of which must be stored, linked and made accessible for users, scientists, collaborators and where appropriate the wider community. The OME Consortium has built several open source tools for managing, linking and sharing these different types of data. The OME Data Model is a metadata specification that supports the image data and metadata recorded in HCS experiments. Bio-Formats is a Java library that reads recorded image data and metadata and includes support for several HCS screening systems. OMERO is an enterprise data management application that integrates image data, experimental and analytic metadata and makes them accessible for visualization, mining, sharing and downstream analysis. We discuss how Bio-Formats and OMERO handle these different data types, and how they can be used to integrate, link and share HCS experiments in facilities and public data repositories. OME specifications and software are open source and are available at https://www.openmicroscopy.org

Mass Homozygotes Accumulation in the NCI-60 Cancer Cell Lines As Compared to HapMap Trios, and Relation to Fragile Site Location

Runs of homozygosity (ROH) represents extended length of homozygotes on a long genomic distance. In oncology, it is known as loss of heterozygosity (LOH) if identified exclusively in cancer cell rather than in matched control cell. Studies have identified several genomic regions which show consistent ROH in different kinds of carcinoma. To query whether this consistency can be observed on broader spectrum, both in more cancer types and in wider genomic regions, we investigated ROH patterns in the National Cancer Institute 60 cancer cell line panel (NCI-60) and HapMap Caucasian healthy trio families. Using results from Affymetrix 500 K SNP arrays, we report a genome wide significant association of ROH regions between the NCI-60 and HapMap samples, with much a higher level of ROH (11 fold) in the cancer cell lines. Analysis shows that more severe ROH found in cancer cells appears to be the extension of existing ROH in healthy state. In the HapMap trios, the adult subgroup had a slightly but significantly higher level (1.02 fold) of ROH than did the young subgroup. For several ROH regions we observed the co-occurrence of fragile sites (FRAs). However, FRA on the genome wide level does not show a clear relationship with ROH regions