Biomaterials for corneal bioengineering

© 2018 IOP Publishing Ltd. Corneal transplantation is an important surgical treatment for many common corneal diseases. However, a worldwide shortage of tissue from suitable corneal donors has meant that many people are not able to receive sight-restoring operations. In addition, rejection is a major cause of corneal transplant failure. Bioengineering corneal tissue has recently gained widespread attention. In order to facilitate corneal regeneration, a range of materials is currently being investigated. The ideal substrate requires sufficient tectonic durability, biocompatibility with cultured cellular elements, transparency, and perhaps biodegradability and clinical compliance. This review considers the anatomy and function of the native cornea as a precursor to evaluating a variety of biomaterials for corneal regeneration including key characteristics for optimal material form and function. The integration of appropriate cells with the most appropriate biomaterials is also discussed. Taken together, the information provided offers insight into the requirements for fabricating synthetic and semisynthetic corneas for in vitro modeling of tissue development and disease, pharmaceutical screening, and in vivo application for regenerative medicine

The association between major depressive disorder, use of antidepressants and bone mineral density (BMD) in men.

OBJECTIVE: Both depression and use of antidepressants have been negatively associated with bone mineral density (BMD) but mainly in studies among postmenopausal women. Therefore, the aim of this study was to investigate these relationships in men. METHODS: Between 2006 and 2011, 928 men (aged 24-98 years) from the Geelong Osteoporosis Study completed a comprehensive questionnaire, clinical measurements and had BMD assessments at the forearm, spine, total hip and total body. Major depressive disorder (MDD) was identified using a structured clinical interview (SCID-I/NP). The cross-sectional associations between BMD and both MDD and antidepressant use were analyzed using multivariable linear regression. RESULTS: Of the study population, 84 (9.1%) men had a single MDD episode, 50 (5.4%) had recurrent episodes and 65 (7.0%) were using antidepressants at the time of assessment. Following adjustments, recurrent MDD was associated with lower BMD at the forearm and total body (-6.5%, P=0.033 and -2.5%, P=0.033, respectively compared to men with no history of MDD), while single MDD episodes were associated with higher BMD at the total hip (+3.4%, P=0.030). Antidepressant use was associated with lower BMD only in lower-weight men (<75-110 kg depending on bone site). CONCLUSIONS: Both depression and use of antidepressants should be taken into account as possible risk factors for osteoporosis in men

Linking population size structure, heat stress and bleaching responses in a subtropical endemic coral

Anthropocene coral reefs are faced with increasingly severe marine heatwaves and mass coral bleaching mortality events. The ensuing demographic changes to coral assemblages can have long-term impacts on reef community organisation. Thus, understanding the dynamics of subtropical scleractinian coral populations is essential to predict their recovery or extinction post-disturbance. Here we present a 10-yr demographic assessment of a subtropical endemic coral, Pocillopora aliciae (Schmidt-Roach et al. in Zootaxa 3626:576–582, 2013) from the Solitary Islands Marine Park, eastern Australia, paired with long-term temperature records. These coral populations are regularly affected by storms, undergo seasonal thermal variability, and are increasingly impacted by severe marine heatwaves. We examined the demographic processes governing the persistence of these populations using inference from size-frequency distributions based on log-transformed planar area measurements of 7196 coral colonies. Specifically, the size-frequency distribution mean, coefficient of variation, skewness, kurtosis, and coral density were applied to describe population dynamics. Generalised Linear Mixed Effects Models were used to determine temporal trends and test demographic responses to heat stress. Temporal variation in size-frequency distributions revealed various population processes, from recruitment pulses and cohort growth, to bleaching impacts and temperature dependencies. Sporadic recruitment pulses likely support population persistence, illustrated in 2010 by strong positively skewed size-frequency distributions and the highest density of juvenile corals measured during the study. Increasing mean colony size over the following 6 yr indicates further cohort growth of these recruits. Severe heat stress in 2016 resulted in mass bleaching mortality and a 51% decline in coral density. Moderate heat stress in the following years was associated with suppressed P. aliciae recruitment and a lack of early recovery, marked by an exponential decrease of juvenile density (i.e. recruitment) with increasing heat stress. Here, population reliance on sporadic recruitment and susceptibility to heat stress underpin the vulnerability of subtropical coral assemblages to climate change

Modelling the optical/UV emission of Swift J0243.6+6124 during its 2017-2018 giant outburst

The Be X-ray binary Swift J0243.6+6124 underwent a super-Eddington giant outburst that lasted from September 2017 to February 2018. The reached luminosity was so high, that it became the first Ultraluminous X-ray pulsar (ULXP) in the Galaxy. Simultaneously to this X-ray outburst, optical and UV outbursts were observed. In this work, we try to explain the origin of this emission. We built a physical model considering the heating of the surface of the Be star, the emission from the viscously heated accretion disk, and the irradiation of this accretion disk by the central Xray source. Using this model, we fit the Spectral Energy Distributions built with the available photometric measurements obtained each day along the outburst

Unveiling the origin of the optical and UV emission during the 2017 giant outburst of the Galactic ULX pulsar Swift J0243.6+6124

Context. From late September 2017 to January 2018, the Be X-ray binary (BeXB) Swift J0243.6+6124 underwent a giant outburst that was unprecedently bright. The reported X-ray luminosities were so high that the system was classified as an ultraluminous X-ray source (ULX). It was also the first BeXB pulsar to show radio jet emission. The source was not only bright in X-rays and radio, but also in the optical and ultraviolet (UV) wavelenghts as well. // Aims. In this work, we aim to understand the origin of the observed optical/UV fluxes simultaneous to the X-ray emission. // Methods. We studied the optical/UV light curves in comparison with the X-ray fluxes along the outburst. We considered the main mechanisms that can explain the optical/UV emission in X-ray binaries. Due to the tight correlation observed between the optical/UV and X-ray light curves, reprocessing of X-rays seems to be the most plausible explanation. We calculated the timescales of the light curve decays and studied the correlation indexes between the optical and X-ray emission. Finally, we built a physical model that considers the X-ray heating of the surface of the donor star, irradiation of the accretion disk, and emission from a viscously heated accretion disk, so that we could reproduce the observed optical/UV spectral energy distributions (SEDs) along the outburst. In our model, we considered the Be circumstellar disk to be co-planar to the orbit and then we neglected its irradiation in the current model. As an input for the model, we used as incident X-ray luminosities those calculated from the bolometric X-ray fluxes obtained from the spectral fit of the Swift/XRT and BAT observations. // Results. The timescales of the exponential decay of the outburst are between two and four times longer for the UV and optical light curves than for the X-ray light curve. The correlation index between the optical/UV and X-ray fluxes varies between optical/UV filters and when different X-ray bands are considered and is larger for the rise than for the decay phase of the outburst for the fluxes at redder wavelengths. The modelling of the SED shows that X-ray heating of the companion star surface is the main mechanism contributing to the UV emission and contributes significantly to the optical emission during the whole outburst. The X-ray irradiation of the accretion disk is necessary to reproduce the optical observed fluxes from MJD 58047 to 58120 and contributes significantly to the UV fluxes close to the peak of the outburst. As a first attempt, the fits yield an increasing value of the outer radius of the accretion disk along the outburst. An alternative interpretation points to variations in the geometry of the inner flow and the fraction of reprocessed X-ray emission during the outburst. On the other hand, variations in the geometry of the Be circumstellar disk could also play a role, but they have not been considered in the current model. // Conclusions. Reprocessing of X-rays via the X-ray heating of the Be star surface and as irradiation of the accretion disk is the main mechanism that can reproduce the observed optical/UV emission during the 2017−2018 giant outburst of Swift J0243.6+6124

Gas-Phase Ambient Air Contaminants Exhibit Significant Dioxin-like and Estrogen-like Activity in Vitro

Several adverse health effects, such as respiratory and cardiovascular morbidity, have been linked to exposure to particulate matter in ambient air; however, the biologic activity of gas-phase ambient organic air contaminants has not been examined as thoroughly. Using aryl hydrocarbon receptor (AHR)–based and estrogen receptor (ER)–based cell bioassay systems, we assessed the dioxin-like and estrogenic activities of gas-phase organic ambient air contaminants compared with those of particulate-phase contaminants using samples collected between seasons over 2 years from an urban and a rural location in the Greater Toronto Area, Canada. The concentration of the sum (∑) of polycyclic aromatic hydrocarbons, which was highest in the gas phase, was 10–100 times more abundant than that of ∑polychlorinated biphenyls, ∑nitro-polycyclic aromatic hydrocarbons, and ∑organochlorine pesticides, and 10(3) to 10(4) times more abundant than ∑polychlorinated dibenzo-p-dioxins/dibenzofurans. Gas-phase samples induced significant AHR- and ER-dependent gene expression. The activity of the gas-phase samples was greater than that of the particulate-phase samples in the estrogen assay and, in one case, in the AHR assay. We found no strong associations between either summer or winter seasons or urban or rural locations in the relative efficacy of the extracts in either the ER or AHR assay despite differences in chemical composition, concentrations, and abundance. Our results suggest that mechanistic studies of the health effects of ambient air must consider gas and particulate phases because chemicals present in both phases can affect AHR and ER signaling pathways

Are uranium-contaminated soil and irrigation water a risk for human vegetable consumers? A study case with Solanum tuberosum L., Phaseolus vulgaris L. and Lactuca sativa L.

The knowledge of uranium concentration, in the products entering the human diet is of extreme importance because of their chemical hazard to health. Controlled field experiments with potatoes, beans and lettuce (Solanum tuberosum L., Phaseolus vulgaris L. and Lactuca sativa L.) were carried out in a contaminated soil used by local farmers located near a closed Portuguese uranium mine (Cunha Baixa, Mangualde). The soil with high average uranium levels (64–252 mg/kg) was divided in two plots, and irrigated with non-contaminated and uranium-contaminated water (\20 and [900 lg/L). Uranium maximum average concentration in the edible vegetables parts (mg/kg fresh weight) ranged in the following order: lettuce (234 lg/kg)[green bean (30 lg/kg)[potatoes without peel (4 lg/kg). Although uranium in soil, irrigation water and vegetables was high, the assessment of the health risk based on hazard quotient indicates that consumption of these vegetables does not represent potential adverse (no carcinogenic) effects for a local inhabitant during lifetime

Distance Optimization and the Extremal Variety of the Grassmann Variety

The approximation of a multivector by a decomposable one is a distance-optimization problem between the multivector and the Grassmann variety of lines in a projective space. When the multivector diverges from the Grassmann variety, then the approximate solution sought is the worst possible. In this paper, it is shown that the worst solution of this problem is achieved, when the eigenvalues of the matrix representation of a related two-vector are all equal. Then, all these pathological points form a projective variety. We derive the equation describing this projective variety, as well as its maximum distance from the corresponding Grassmann variety. Several geometric and algebraic properties of this extremal variety are examined, providing a new aspect for the Grassmann varieties and the respective projective spaces

Deep reinforcement learning for drone navigation using sensor data

Mobile robots such as unmanned aerial vehicles (drones) can be used for surveillance, monitoring and data collection in buildings, infrastructure and environments. The importance of accurate and multifaceted monitoring is well known to identify problems early and prevent them escalating. This motivates the need for flexible, autonomous and powerful decision-making mobile robots. These systems need to be able to learn through fusing data from multiple sources. Until very recently, they have been task specific. In this paper, we describe a generic navigation algorithm that uses data from sensors on-board the drone to guide the drone to the site of the problem. In hazardous and safety-critical situations, locating problems accurately and rapidly is vital. We use the proximal policy optimisation deep reinforcement learning algorithm coupled with incremental curriculum learning and long short-term memory neural networks to implement our generic and adaptable navigation algorithm. We evaluate different configurations against a heuristic technique to demonstrate its accuracy and efficiency. Finally, we consider how safety of the drone could be assured by assessing how safely the drone would perform using our navigation algorithm in real-world scenarios

Poxvirus-based vaccine therapy for patients with advanced pancreatic cancer

<p>Abstract</p> <p>Purpose</p> <p>An open-label Phase 1 study of recombinant prime-boost poxviruses targeting CEA and MUC-1 in patients with advanced pancreatic cancer was conducted to determine safety, tolerability and obtain preliminary data on immune response and survival.</p> <p>Patients and methods</p> <p>Ten patients with advanced pancreatic cancer were treated on a Phase I clinical trial. The vaccination regimen consisted of vaccinia virus expressing tumor antigens carcinoembryonic antigen (CEA) and mucin-1 (MUC-1) with three costimulatory molecules B7.1, ICAM-1 and LFA-3 (TRICOM) (PANVAC-V) and fowlpox virus expressing the same antigens and costimulatory molecules (PANVAC-F). Patients were primed with PANVAC-V followed by three booster vaccinations using PANVAC-F. Granulocyte-macrophage colony-stimulating factor (GM-CSF) was used as a local adjuvant after each vaccination and for 3 consecutive days thereafter. Monthly booster vaccinations for up to 12 months were provided for patients without progressive disease. Peripheral blood was collected before, during and after vaccinations for immune analysis.</p> <p>Results</p> <p>The most common treatment-related adverse events were mild injection-site reactions. Antibody responses against vaccinia virus was observed in all 10 patients and antigen-specific T cell responses were observed in 5 out of 8 evaluable patients (62.5%). Median overall survival was 6.3 months and a significant increase in overall survival was noted in patients who generated anti CEA- and/or MUC-1-specific immune responses compared with those who did not (15.1 vs 3.9 months, respectively; <it>P </it>= .002).</p> <p>Conclusion</p> <p>Poxvirus vaccination is safe, well tolerated, and capable of generating antigen-specific immune responses in patients with advanced pancreatic cancer.</p