Functional impairment of reading in patients with dry eye

BACKGROUND/AIMS: To evaluate the impact of dry eye on reading performance. METHODS: Out-loud and silent reading in patients with clinically significant dry eye (n=41) and controls (n=50) was evaluated using standardised texts. Dry eye measures included tear film break-up time, Schirmer's test and corneal epithelial staining. Symptoms were assessed by the Ocular Surface Disease Index (OSDI). RESULTS: The dry eye group had a greater proportion of women as compared with the control group but did not differ in age, race, education level or visual acuity (p≥0.05 for all). Out-loud reading speed averaged 148 words per minute (wpm) in dry eye subjects and 163 wpm in controls (p=0.006). Prolonged silent reading speed averaged 199 wpm in dry eye subjects versus 226 wpm in controls (p=0.03). In multivariable regression models, out-loud and sustained silent reading speeds were 10 wpm (95% CI −20 to −1 wpm, p=0.039) and 14% (95% CI −25% to −2%, p=0.032) slower, respectively, in dry eye subjects as compared with controls. Greater corneal staining was associated with slower out-loud (−2 wpm/1 unit increase in staining score, 95% CI =−3 to −0.3 wpm) and silent (−2%, 95% CI −4 to −0.6 wpm) reading speeds (p<0.02 for both). Significant interactions were found between OSDI score and word-specific features (longer and less commonly used words) on out-loud reading speed (p<0.05 for both). CONCLUSIONS: Dry eye is associated with slower out-loud and silent reading speeds, providing direct evidence regarding the functional impact of dry eye. Reading speed represents a measurable clinical finding that correlates directly with dry eye severity

International Public Health Research Involving Interpreters: a Case Study from Bangladesh

Background: Cross-cultural and international research are important components of public health research, but the challenges of language barriers and working with interpreters are often overlooked, particularly in the case of qualitative research. Methods: A case-study approach was used to explore experiences of working with an interpreter in Bangladesh as part of a research project investigating women's experiences of emergency obstetric care. The case study: Data from the researcher's field notes provided evidence of experiences in working with an interpreter and show how the model of interviewing was adapted over time to give a more active role to the interpreter. The advantages of a more active role were increased rapport and "flow" in interviews. The disadvantages included reduced control from the researcher's perspective. Some tensions between the researcher and interpreter remained hard to overcome, irrespective of the model used. Independent transcription and translation of the interviews also raised questions around accuracy in translation. Conclusion: The issues examined in this case study have broader implications for public health research. Further work is needed in three areas: 1) developing effective relationships with interpreters; 2) the impact of the interpreter on the research process; and 3) the accuracy of the translation and level of analysis needed in any specific public health research. Finally, this paper highlights the importance to authors of reflecting on the potential impact of translation and interpretation on the research process when disseminating their research

Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition

BACKGROUND:Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.METHODS:We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.RESULTS:All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.CONCLUSIONS:Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations

Genome Editing Technology, CRISPR Cas-9, Provides a Potential Future for Xenotransplantation: Can Pigs Become Our New Organ Donors?

Organ shortage has been a significant issue in United States for many decades. There were over 116,000 people on the transplant waiting list as of August 2017, with a new person added every 10 minutes. Animals have been considered as potential organ donors for humans, with the pig being the most ideal candidate because of its excellent breeding profile, low maintenance costs, large litters, rapid growth and organ similarity. A notable challenge that comes with porcine organs are endogenous retroviruses that establish themselves in the DNA of offspring in utero, thereby allowing for no time to prevent infection and integration. Porcine endogenous retroviruses (PERVs) have the ability to infect human cells and therefore must be removed or inactivated before considering transplantation. Genome editing technology, CRISPR-cas9, has been recently successful in targeting and inactivating PERVs in porcine fetal cell lines. Using PERVinactivated cells, reproductive technologies have allowed for fertilization, implantation and the successful birth of 37 PERV-inactivated piglets from 17 sows. At this time, 15 piglets remain alive with the oldest piglet being 4 months of age. The success of this technology takes us one step closer to finding potential organ donors outside of our own species and instilling hope back into those who may need an organ transplant in the future

Cellular responses of Candida albicans to phagocytosis and the extracellular activities of neutrophils are critical to counteract carbohydrate starvation, oxidative and nitrosative stress

Acknowledgments We thank Alexander Johnson (yhb1D/D), Karl Kuchler (sodD/D mutants), Janet Quinn (hog1D/D, hog1/cap1D/D, trx1D/D) and Peter Staib (ssu1D/D) for providing mutant strains. We acknowledge helpful discussions with our colleagues from the Microbial Pathogenicity Mechanisms Department, Fungal Septomics and the Microbial Biochemistry and Physiology Research Group at the Hans Kno¨ll Institute (HKI), specially Ilse D. Jacobsen, Duncan Wilson, Sascha Brunke, Lydia Kasper, Franziska Gerwien, Sea´na Duggan, Katrin Haupt, Kerstin Hu¨nniger, and Matthias Brock, as well as from our partners in the FINSysB Network. Author Contributions Conceived and designed the experiments: PM HW IMB AJPB OK BH. Performed the experiments: PM CD HW. Analyzed the data: PM HW IMB AJPB OK BH. Wrote the paper: PM HW OK AJPB BH.Peer reviewedPublisher PD

Marginalization of end-use technologies in energy innovation for climate protection

Mitigating climate change requires directed innovation efforts to develop and deploy energy technologies. Innovation activities are directed towards the outcome of climate protection by public institutions, policies and resources that in turn shape market behaviour. We analyse diverse indicators of activity throughout the innovation system to assess these efforts. We find efficient end-use technologies contribute large potential emission reductions and provide higher social returns on investment than energy-supply technologies. Yet public institutions, policies and financial resources pervasively privilege energy-supply technologies. Directed innovation efforts are strikingly misaligned with the needs of an emissions-constrained world. Significantly greater effort is needed to develop the full potential of efficient end-use technologies

Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation

Background: Autologous keratincoytes are routinely expanded using irradiated mouse fibroblasts and bovine serum for clinical use. With growing concerns about the safety of these xenobiotic materials, it is desirable to culture keratinocytes in media without animal derived products. An improved understanding of epithelial/mesenchymal interactions could assist in this. Methodology/Principal Findings: A keratincyte/fibroblast o-culture model was developed by extending an agent-based keratinocyte colony formation model to include the response of keratinocytes to both fibroblasts and serum. The model was validated by comparison of the in virtuo and in vitro multicellular behaviour of keratinocytes and fibroblasts in single and co-culture in Greens medium. To test the robustness of the model, several properties of the fibroblasts were changed to investigate their influence on the multicellular morphogenesis of keratinocyes and fibroblasts. The model was then used to generate hypotheses to explore the interactions of both proliferative and growth arrested fibroblasts with keratinocytes. The key predictions arising from the model which were confirmed by in vitro experiments were that 1) the ratio of fibroblasts to keratinocytes would critically influence keratinocyte colony expansion, 2) this ratio needed to be optimum at the beginning of the co-culture, 3) proliferative fibroblasts would be more effective than irradiated cells in expanding keratinocytes and 4) in the presence of an adequate number of fibroblasts, keratinocyte expansion would be independent of serum. Conclusions: A closely associated computational and biological approach is a powerful tool for understanding complex biological systems such as the interactions between keratinocytes and fibroblasts. The key outcome of this study is the finding that the early addition of a critical ratio of proliferative fibroblasts can give rapid keratinocyte expansion without the use of irradiated mouse fibroblasts and bovine serum

Biotic and abiotic retention, recycling and remineralization of metals in the ocean

Trace metals shape both the biogeochemical functioning and biological structure of oceanic provinces. Trace metal biogeochemistry has primarily focused on modes of external supply of metals from aeolian, hydrothermal, sedimentary and other sources. However, metals also undergo internal transformations such as abiotic and biotic retention, recycling and remineralization. The role of these internal transformations in metal biogeochemical cycling is now coming into focus. First, the retention of metals by biota in the surface ocean for days, weeks or months depends on taxon-specific metal requirements of phytoplankton, and on their ultimate fate: that is, viral lysis, senescence, grazing and/or export to depth. Rapid recycling of metals in the surface ocean can extend seasonal productivity by maintaining higher levels of metal bioavailability compared to the influence of external metal input alone. As metal-containing organic particles are exported from the surface ocean, different metals exhibit distinct patterns of remineralization with depth. These patterns are mediated by a wide range of physicochemical and microbial processes such as the ability of particles to sorb metals, and are influenced by the mineral and organic characteristics of sinking particles. We conclude that internal metal transformations play an essential role in controlling metal bioavailability, phytoplankton distributions and the subsurface resupply of metals

Exclusive ρ0\rho^0 electroproduction on the proton at CLAS

The $e p\to e^\prime p \rho^0$ reaction has been measured, using the 5.754 GeV electron beam of Jefferson Lab and the CLAS detector. This represents the largest ever set of data for this reaction in the valence region. Integrated and differential cross sections are presented. The $W$, $Q^2$ and $t$ dependences of the cross section are compared to theoretical calculations based on $t$-channel meson-exchange Regge theory on the one hand and on quark handbag diagrams related to Generalized Parton Distributions (GPDs) on the other hand. The Regge approach can describe at the $\approx$ 30% level most of the features of the present data while the two GPD calculations that are presented in this article which succesfully reproduce the high energy data strongly underestimate the present data. The question is then raised whether this discrepancy originates from an incomplete or inexact way of modelling the GPDs or the associated hard scattering amplitude or whether the GPD formalism is simply inapplicable in this region due to higher-twists contributions, incalculable at present.Comment: 29 pages, 29 figure

Photodisintegration of 4^4He into p+t

The two-body photodisintegration of $^4$He into a proton and a triton has been studied using the CEBAF Large-Acceptance Spectrometer (CLAS) at Jefferson Laboratory. Real photons produced with the Hall-B bremsstrahlung-tagging system in the energy range from 0.35 to 1.55 GeV were incident on a liquid $^4$He target. This is the first measurement of the photodisintegration of $^4$He above 0.4 GeV. The differential cross sections for the $\gamma$$^4$He$\to pt$ reaction have been measured as a function of photon-beam energy and proton-scattering angle, and are compared with the latest model calculations by J.-M. Laget. At 0.6-1.2 GeV, our data are in good agreement only with the calculations that include three-body mechanisms, thus confirming their importance. These results reinforce the conclusion of our previous study of the three-body breakup of $^3$He that demonstrated the great importance of three-body mechanisms in the energy region 0.5-0.8 GeV .Comment: 13 pages submitted in one tgz file containing 2 tex file and 22 postscrip figure