Plant-Made Vaccine Antigens and Biopharmaceuticals

Plant cells are ideal bioreactors for the production and oral delivery of vaccines and biopharmaceuticals, eliminating the need for expensive fermentation, purification, cold storage, transportation and sterile delivery. Plant-made vaccines have been developed for two decades but none has advanced beyond Phase I. However, two plant-made biopharmaceuticals are now advancing through Phase II and Phase III human clinical trials. In this review, we evaluate the advantages and disadvantages of different plant expression systems (stable nuclear and chloroplast or transient viral) and their current limitations or challenges. We provide suggestions for advancing this valuable concept for clinical applications and conclude that greater research emphasis is needed on large scale production, purification, functional characterization, oral delivery and preclinical evaluation

A Super-Earth and Two Neptunes Orbiting the Nearby Sun-like Star 61 Virginis

We present precision radial velocity data that reveal a multiple exoplanet system orbiting the bright nearby G5V star 61 Virginis. Our 4.6 years of combined Keck/HIRES and Anglo-Australian Telescope precision radial velocities indicate the hitherto unknown presence of at least three planets orbiting this well-studied star. These planets are all on low-eccentricity orbits with periods of 4.2, 38.0, and 124.0 days, and projected masses (Msin i) of 5.1, 18.2, and 24.0 M_⊕, respectively. Test integrations of systems consistent with the radial velocity data suggest that the configuration is dynamically stable. Depending on the effectiveness of tidal dissipation within the inner planet, the inner two planets may have evolved into an eccentricity fixed-point configuration in which the apsidal lines of all three planets corotate. This conjecture can be tested with additional observations. We present a 16-year time series of photometric observations of 61 Virginis, which comprise 1194 individual measurements, and indicate that it has excellent photometric stability. No significant photometric variations at the periods of the proposed planets have been detected. This new system is the first known example of a G-type Sun-like star hosting a Super-Earth mass planet. It joins HD 75732 (55 Cnc), HD 69830, GJ 581, HD 40307, and GJ 876 in a growing group of exoplanet systems that have multiple planets orbiting with periods less than an Earth-year. The ubiquity of such systems portends that space-based transit-search missions such as Kepler and CoRoT will find many multi-transiting systems

Natural History of Geographic Atrophy Secondary to Age-Related Macular Degeneration: Results from the Prospective Proxima A and B Clinical Trials.

Abstract Purpose To better characterize visual function decline and geographic atrophy (GA) progression secondary to age-related macular degeneration (AMD). Design Proxima A (NCT02479386) and Proxima B (NCT02399072) were global, prospective, non-interventional, observational clinical trials. Participants Eligible patients were aged ≥50 years. Patients in Proxima A had bilateral GA without choroidal neovascularization (CNV) in either eye (N=295). Patients in Proxima B had GA with no CNV in the study eye and CNV±GA in the fellow eye (fellow eye CNV cohort, n=168); or GA with no CNV in the study eye, without CNV/GA in the fellow eye (fellow eye intermediate AMD cohort, n=32). Methods Changes in visual function and imaging/anatomic parameters were evaluated over time using a Mixed Model for Repeated Measurement (MMRM) accounting for key baseline characteristics. Main Outcome Measures Pre-specified endpoints included change in GA area from baseline, best corrected visual acuity (BCVA) score assessed by ETDRS, and BCVA under low-luminance conditions (LLVA). Results At 24 months, the adjusted mean (standard error; SE) change in GA lesion area from baseline was 3.87 (0.15) mm2 in participants with bilateral GA (Proxima A), 3.55 (0.16) mm2 in the fellow eye CNV cohort (Proxima B), and 2.96 (0.25) mm2 in the fellow eye intermediate AMD cohort (Proxima B). GA progression was greater in patients with baseline non-subfoveal (vs. subfoveal) GA lesions, and tended to increase as baseline low-luminance deficit increased (Proxima A; Proxima B, all patients). Conversion to GA or CNV in the fellow eye occurred in 30% and 6.7% of participants, respectively, in the Proxima B intermediate AMD cohort at month 12. Adjusted mean (SE) changes in BCVA and LLVA (ETDRS letters) in the study eye from baseline to 24 months: −13.88 (1.40) and −7.64 (1.20) in Proxima A, −9.49 (1.29) and −7.57 (1.26) in the Proxima B fellow eye CNV cohort, −11.48 (3.39) and −8.37 (3.02) in the Proxima B fellow eye intermediate AMD cohort, respectively. Conclusions The prospective Proxima A and B studies highlight the severe functional impact of GA and the rapid rate of GA lesion progression over a 2-year period, including in patients with unilateral GA at baseline

Evidence for Reflected Light from the Most Eccentric Exoplanet Known

This is an author-created, un-copyedited version of an article published in The Astrophysical Journal. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at https://doi.org/10.3847/0004-637X/821/1/65.Planets in highly eccentric orbits form a class of objects not seen within our solar system. The most extreme case known among these objects is the planet orbiting HD20782, with an orbital period of 597days and an eccentricity of 0.96. Here we present new data and analysis for this system as part of the Transit Ephemeris Refinement and Monitoring Survey. We obtained CHIRON spectra to perform an independent estimation of the fundamental stellar parameters. New radial velocities from Anglo-Australian Telescope and PARAS observations during periastron passage greatly improve our knowledge of the eccentric nature of the orbit. The combined analysis of our Keplerian orbital and Hipparcos astrometry show that the inclination of the planetary orbit is >1.22, ruling out stellar masses for the companion. Our long-term robotic photometry show that the star is extremely stable over long timescales. Photometric monitoring of the star during predicted transit and periastron times using Microvariability and Oscillations of STars rule out a transit of the planet and reveal evidence of phase variations during periastron. These possible photometric phase variations may be caused by reflected light from the planet’s atmosphere and the dramatic change in star–planet separation surrounding the periastron passage.Peer reviewedFinal Accepted Versio

Photodynamic versus white light-guided treatment of non-muscle invasive bladder cancer: a study protocol for a randomised trial of clinical and cost-effectiveness

Bladder cancer is the most frequently occurring tumour of the urinary system. Ta, T1 tumours and carcinoma in situ (CIS) are grouped as non-muscle invasive bladder cancer (NMIBC), which can be effectively treated by transurethral resection of bladder tumour (TURBT). There are limitations to the visualisation of tumours with conventional TURBT using white light illumination within the bladder. Incomplete resections occur from the failure to identify satellite lesions or the full extent of the tumour leading to recurrence and potential risk of disease progression. To improve complete resection, photodynamic diagnosis (PDD) has been proposed as a method that can enhance tumour detection and guide resection. The objective of the current research is to determine whether PDD-guided TURBT is better than conventional white light surgery and whether it is cost-effective.This article is freely available via Open Access. Click on the publisher URL to access the full-text from the publisher's site

Evidence for reflected light from the most eccentric exoplanet known

Planets in highly eccentric orbits form a class of objects not seen within our Solar System. The most extreme case known amongst these objects is the planet orbiting HD 20782, with an orbital period of 597 days and an eccentricity of 0.96. Here we present new data and analysis for this system as part of the Transit Ephemeris Refinement and Monitoring Survey (TERMS). We obtained CHIRON spectra to perform an independent estimation of the fundamental stellar parameters. New radial velocities from AAT and PARAS observations during periastron passage greatly improve the our knowledge of the eccentric nature of the orbit. The combined analysis of our Keplerian orbital and Hipparcos astrometry show that the inclination of the planetary orbit is > 1.25 degrees, ruling out stellar masses for the companion. Our long-term robotic photometry show that the star is extremely stable over long timescales. Photometric monitoring of the star during predicted transit and periastron times using MOST rule out a transit of the planet and reveal evidence of phase variations during periastron. These possible photometric phase variations are likely caused by reflected light from the planet's atmosphere and the dramatic change in star--planet separation surrounding the periastron passage

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions associated with the presence of carotid plaque (P < 5 × 10 -8). The associated SNPs mapped in or near genes related to cellular signaling, lipid metabolism and blood pressure homeostasis, and two of the regions were associated with coronary artery disease (P < 0.006) in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) consortium. Our findings may provide new insight into pathways leading to subclinical atherosclerosis and subsequent cardiovascular events