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In April 2018, a significant cave entrance was recognized during an aerial survey in Wells Gray Provincial Park, British Columbia. A September 2018 assessment of the site confirmed one of the largest known, and previously undocumented, cave entrances in Canada. The feature is a large vertically walled sink swallowing a small river, likely leading to a spring 2.16 km horizontally from, and 460 m below, the sink. The entrance shaft was partially descended, surveyed, and found to have a volume of over 450 000 m3. Formed in a carbonate unit of the upper Proterozoic Horsethief Creek Group, the cave entrance occurs in stripe karst extending well beyond the known cave drainage. The disappearing river drains an area of 6.3 km2 in a valley containing two small glaciers. The river has a low flow (September) rate estimated at 0.3–0.5 m3/s, comparable with some of the largest sinks in Canada. Historic aerial photographs of the area show the entrance was hidden by perennial snowfields until regional climatic warming caused the snow plug to collapse sometime within the past decade.

Purpose To compare 2.0 mg ranibizumab (RBZ) injections with 0.5 mg RBZ for eyes with center-involved diabetic macular edema (DME). Design Randomized, controlled, double-masked (to the dose), interventional, multicenter clinical trial. Participants A total of 152 patients (152 eyes) with DME. Methods Eligible eyes were randomized in a 1:1 ratio to 0.5 mg (n = 77) or 2.0 mg (n = 75) RBZ. Study eyes received 6 monthly mandatory injections followed by as-needed injections until month 24. Main Outcome Measures The primary efficacy end point of the study was mean change in best-corrected visual acuity (BCVA) and central foveal thickness (CFT) at month 6. Secondary outcomes included the mean change in BCVA and CFT at month 24, and incidence and severity of systemic and ocular adverse events through month 24. Results A total of 152 eyes were randomized in the study. At month 24, the mean improvement from baseline BCVA was +11.06 letters in the 0.5 mg RBZ group (n = 59) and +6.78 letters in the 2.0 mg RBZ group (n = 54) ( P = 0.02). The mean numbers of RBZ injections through month 24 were 18.4 and 17.3 in the 0.5 mg and 2.0 mg RBZ groups, respectively ( P = 0.08). The mean change in CFT was −192.53 μm in the 0.5 mg RBZ group and −170.64 μm in the 2.0 mg RBZ group ( P = 0.41). By month 24, 3 deaths had occurred in the 0.5 mg RBZ group and 3 deaths had occurred in the 2.0 mg RBZ group; 5 of these 6 deaths occurred secondary to cardiovascular causes, and 1 death occurred as the result of severe pneumonia. All 5 patients with a cardiovascular cause of death had a history of coronary heart disease. Conclusions At month 24, there were significant visual and anatomic improvements in both groups, with subjects in the 0.5 mg RBZ group gaining more vision. Visual and anatomic gains achieved at month 6 were largely maintained through month 24. No new safety events were identified. In this study population, 2.0 mg RBZ does not appear to provide additional benefit over 0.5 mg RBZ.

Current genome-wide association studies (GWAS) are subject to misleading results given variation in linkage disequilibrium between SNP and causative variants and the potential for misidentification between genotypes and associated phenotypes. Consequently, the current study conducted a GWAS utilizing the Geneseek Genomic Profiler F250K panel to identify SNP associated with carcass traits, assess the effects of mismatching various percentages (5–50%) of phenotypes and genotypes, and to evaluate the benefits of the GGP F250K panel in comparison to a lower density panel. After editing, data were available on 745 animals for marbling (MARB), ribeye area (REA), carcass weight (CW), and backfat (FAT), and 221,115 SNP. A Bayes C model with fixed effects of birth year/season, harvest date, and linear covariate of age was employed with π set to 0.998. Results are the posterior means of 50,000 iterations after discarding 2,000 as burn-in. A lower density panel (LD) of 39,295 SNP in common between the Illumina 50K, GGP F250K, and Illumina BovineHD (777K) was created for comparison to the GGP F250K panel. To create mismatches between genotypes and phenotypes, a random sample (5–50%) of animals were selected from the phenotypes, permutated, then analyzed with the same model. This was repeated 5 times for each proportion of mismatches. As the proportion of mismatches increased, posterior heritability estimates decreased. Correlations between 1-Mb windows based on the proportion of variation between the GGP F250K and the LD panels were: 0.588 MARB, 0.764 REA, 0.797 CW, and 0.514 FAT. Ranges in posterior heritability estimates for mismatches of phenotypes and genotypes from 0–50% were: MARB (0.112-0.091), REA (0.477-0.172), CW (0.252-0.076), and FAT (0.085-0.080). Results suggest that re-ranking of 1-Mb windows would be expected between these two panels, and that GWAS studies with limited individuals are highly sensitive to mismatches between genotypes and phenotypes.

Adoption of DNA technology in the beef industry has experienced an accelerating trajectory. The well-accepted and adopted applications are now parentage testing and, more recently, the inclusion of marker data into genetic evaluation systems to produce “genomic enhanced EPDs” (GE-EPD). Neither of these applications requires the markers to be functional variants; however, to produce GE-EPD’s does require the traits (or correlated traits) be in the suite of traits for which EPDs are produced. This does not allow for expansion of the use of the technology to several novel, economically important characteristics. To do so requires discovery populations closely related to the target population if typical marker panels are used and would require retraining as the target population moves away from the discovery population in its degree of relatedness. Knowledge of functional mutations is hypothesized to eliminate the necessity of a closely related population to the point of potentially universal application (across breeds) of the variant contribution to the phenotype(s) of interest. Applications that would then represent significant contribution to the genetic and management programs in beef production would be in the segments of the industry “downstream” of the seedstock industry. Breed independent predictive panels for commercial heifer replacement selection, for feedlot animal management and for product characteristics are fertile ground for the use of functional variants. These applications would target predicting animal performance, and as such would also allow for non-additive effects to be considered. If the variant tool is built as one panel including traits of interest to each segment of the industry, then valuable information becomes available each time ownership of the animal, or products derived from harvesting that animal, occurs.