Dexamethasone intravitreal implant in previously treated patients with diabetic macular edema : Subgroup analysis of the MEAD study

Background: Dexamethasone intravitreal implant 0.7 mg (DEX 0.7) was approved for treatment of diabetic macular edema (DME) after demonstration of its efficacy and safety in the MEAD registration trials. We performed subgroup analysis of MEAD study results to evaluate the efficacy and safety of DEX 0.7 treatment in patients with previously treated DME. Methods: Three-year, randomized, sham-controlled phase 3 study in patients with DME, best-corrected visual acuity (BCVA) of 34.68 Early Treatment Diabetic Retinopathy Study letters (20/200.20/50 Snellen equivalent), and central retinal thickness (CRT) 65300 \u3bcm measured by time-domain optical coherence tomography. Patients were randomized to 1 of 2 doses of DEX (0.7 mg or 0.35 mg), or to sham procedure, with retreatment no more than every 6 months. The primary endpoint was 6515-letter gain in BCVA at study end. Average change in BCVA and CRT from baseline during the study (area-under-the-curve approach) and adverse events were also evaluated. The present subgroup analysis evaluated outcomes in patients randomized to DEX 0.7 (marketed dose) or sham based on prior treatment for DME at study entry. Results: Baseline characteristics of previously treated DEX 0.7 (n = 247) and sham (n=261) patients were similar. In the previously treated subgroup, mean number of treatments over 3 years was 4.1 for DEX 0.7 and 3.2 for sham, 21.5 % of DEX 0.7 patients versus 11.1 % of sham had 6515-letter BCVA gain from baseline at study end (P = 0.002), mean average BCVA change from baseline was +3.2 letters with DEX 0.7 versus +1.5 letters with sham (P = 0.024), and mean average CRT change from baseline was -126.1 \u3bcm with DEX 0.7 versus -39.0 \u3bcm with sham(P < 0.001). Cataract-related adverse events were reported in 70.3 % of baseline phakic patients in the previously treated DEX 0.7 subgroup; vision gains were restored following cataract surgery. Conclusions: DEX 0.7 significantly improved visual and anatomic outcomes in patients with DME previously treated with laser, intravitreal anti-vascular endothelial growth factor, intravitreal triamcinolone acetonide, or a combination of these therapies. The safety profile of DEX 0.7 in previously treated patients was similar to its safety profile in the total study population

Water abstraction from dambos using treadle pumps

This paper provides a “rule of thumb” for estimating the inflow of water into dambos and presents a simple method for estimating an upper limit to the number of treadle pumps that can safely be used on a dambo

Shigella flexneri targets human colonic goblet cells by O antigen binding to Sialyl-Tn and Tn antigens via glycan-glycan interactions

Shigella flexneri targets colonic cells in humans to initiate invasive infection processes that lead to dysentery, and direct interactions between their lipopolysaccharide O antigens and blood group A related glycans are involved in the cell adherence interactions. Here, we show that treatment with Tn and sialyl-Tn glycans, monoclonal antibodies and lectins reactive to Tn/sialyl-Tn, and luteolin (a Tn antigen synthesis inhibitor) all significantly inhibited S. flexneri adherence and invasion of cells in vitro. Surface plasmon resonance analysis showed that lipopolysaccharide O antigen had a high affinity interaction with Tn/sialyl-Tn. Immunofluorescence probing of human colon tissue with antibodies detected expression of Tn/sialyl-Tn by MUC2 producing goblet cells (GCs), and S. flexneri incubated with human colon tissue colocalized with GCs. Our findings demonstrate that S. flexneri targets GCs in the human colonic crypts via glycan-glycan interactions, establishing new insight into the infection process in humans.Elizabeth Ngoc Hoa Tran, Christopher J. Day, Erin McCartney, Jessica Poole, Edmund Tse, Michael P. Jennings, and Renato Moron

Comparative assessment of widespread irrigation with low quality mine-water in undisturbed and rehabilitated mine-lands in the upper Olifants using the ACRU2000 model

The ACRU agrohydrological model, in the form of ACRU2000 and its salinity module, ACRUSalinity, was employed in catchment-scale assessment of widespread irrigation with low quality mine-water in undisturbed (un-mined) and rehabilitated soils in the Upper Olifants basin of South Africa. The study area comprised a small catchment of 4.7 km2 located in a coal-mine environment, known as the Tweefontein Pan catchment. The catchment drained to a surface reservoir (Tweefontein Reservoir) of maximum capacity and surface area 4 000 Mℓ and 1.5 km2, respectively. The catchment was instrumented to measure hydrodynamic responses and simulated as a hydrological system. Consideration was given to runoff, groundwater storage, evapotranspiration, baseflow, interception, irrigation water supply and rainfall, thereby accounting for all the dominant hydrological components of the system. Three scenarios were simulated using the available records for 5 years (1999 to 2004). The first was a baseline scenario representing the prevailing condition in the study area and the other 2 scenarios represented widespread irrigation with the mine-water on undisturbed and rehabilitated soils. In simulating the widespread irrigation on rehabilitated soils, a distinction was made between a rehabilitated irrigated area before and after the re-establishment of the equilibrium water table. Comparison of the results from the simulated scenarios indicated that a greater undisturbed area (max of 160 ha) than rehabilitated area (max of 120 ha) could be irrigated with mine-water from the Tweefontein Reservoir. Irrigation on rehabilitated soils depleted the water in the reservoir more rapidly than irrigation on undisturbed soils, due to lower runoff and higher ingress to groundwater in rehabilitated areas.Keywords: mine-water, widespread irrigation, mined land irrigation, Upper Olifants, catchment scale, hydrological assessment, ACRU200

Assessment of the impact of irrigation with low-quality mine water on virgin and rehabilitated soils in the upper Olifants basin

Low-quality mine water from collieries may be used in large quantities to irrigate agricultural crops on virgin (unmined) and rehabilitated soils in South Africa. Such a use could enhance crop production and allow environmentally sustainable mine water disposal. In this study, the volume and qualities of the runoff from two centre pivots irrigated with moderately saline mine water, as well as their soil water salinities, were monitored and used to determine water and salt balances, using the modified ACRU agrohydrological model, ACRU2000, and its salinity module, ACRUSalinity. At both sites, much of the water evaporated, while a significant part of the salt input either precipitated or remained with the water in the soil horizons. A higher percentage of drainage water (and salinity) were retained as ground water storage and a lower percentage of runoff occurred in the rehabilitated sandy loam soil, while a higher percentage of salts accompanied runoff in the virgin clayey soils. Simulated salt saturation values indicate that many crops could be successfully irrigated at 100% yield potential at either site. Electrical resistivity surveys were carried out at both sites. A general decrease in resistivities with depth in both the virgin and rehabilitated soils reflected the decreasing influence of the mine water used for irrigation with depth and the precipitation of salts in the soils close to the ground surface. The occurrence of a thicker, low-resistivity, near-surface layer near the exit of each pivot area indicates that the water and salt content of the subsurface increased in the direction that the surface and near-surface irrigation water flowed