Analyzing retraction responses of Tubifex tubifex (Oligochaeta: Naididae) colonies to copper treatments through a digital image analysis approach for developing early biological warning systems.

Biological monitoring and assessments are commonly used for sustainable ecosystem management. Oligochaetes are found in various freshwater ecosystems and have been used as indicators of water quality and for the biological assessment of aquatic ecosystems. Among aquatic oligochaetes, the sludge worm Tubifex tubifex (Oligochaeta, Naididae) is tolerant to organic pollution and has been used as a biomonitoring indicator of toxicity and organic pollution. In this study, we investigated the response of worm colonies to copper (CuSO4) treatments (0.01, 0.05, 0.1, 0.5, and 1.0 mg/L) in an observation cage (100 mL beaker) for 30 min. Using a digital image analysis approach, we measured the changes in the colony image area between pre- and post-copper treatment. After copper treatment, the colony image area tended to decrease, even at low copper concentrations. In addition, the colony areas did not recover to their original levels at high concentrations, although those at low concentrations did. Area decreased proportional to the logarithm of the copper concentration. Finally, our results present the possible use of the retraction responses of Tubifex tubifex colonies to chemical disturbances as early biological warning systems.

Biosimilar candidate CT-P42 in diabetic macular edema: 24-week results from a randomized, active-controlled, Phase III study.

OBJECTIVE: To demonstrate the therapeutic similarity of CT-P42 compared to reference aflibercept (Eylea®) in adult patients with diabetic macular edema (DME). DESIGN: Randomized, active-controlled, double-masked, Phase III clinical trial PARTICIPANTS: Patients with a diagnosis of either type 1 or 2 diabetes mellitus (DM) with DME involving the center of the macula. METHODS: Patients were randomized (1:1) to receive either CT-P42 or reference aflibercept (2 mg/0.05 mL) by intravitreal injection every 4 weeks (5 doses) then every 8 weeks (4 doses) in the main study period. Results up to Week 24 are reported herein. MAIN OUTCOME MEASURES: The primary endpoint was mean change from baseline at Week 8 in best corrected visual acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Equivalence between CT-P42 and reference aflibercept was to be concluded if the two-sided 95% confidence interval (CI) (global assumptions) and two-sided 90% CI (US Food and Drug Administration [FDA] assumptions) for the treatment difference fell entirely within the equivalence margin of ±3 letters, as assessed in the full analysis set. RESULTS: Overall, 348 patients were randomized (CT-P42: 173; reference aflibercept: 175). BCVA improved from baseline to Week 8 in both groups, with a least squares mean (standard error) improvement of 9.43 (0.798) and 8.85 (0.775) letters in the CT-P42 and reference aflibercept groups, respectively. The estimated between-group treatment difference was 0.58 letters, with the CIs within the pre-defined equivalence margin of ±3 letters (95% CI -0.73, 1.88 [global]; 90% CI -0.52, 1.67 [FDA]). Through Week 24, other efficacy results for the two groups, in terms of change in BCVA and retinal central subfield thickness, as well as ETDRS Diabetic Retinopathy Severity Scale score, supported therapeutic similarity. Pharmacokinetics, usability, safety (including the proportions of patients experiencing at least one treatment-emergent adverse event [CT-P42: 50.3%; reference aflibercept: 53.7%]), and immunogenicity were also comparable between groups. CONCLUSIONS: This study in patients with DME demonstrated equivalence between CT-P42 and reference aflibercept (2 mg/0.05 mL) in terms of efficacy, with similar pharmacokinetic, usability, safety, and immunogenicity profiles.