consequently, mortality associated with CNDD. This mechanism allows rare species to avoid a disadvantage-when-rare that would, all else equal, result from stronger CNDD in rare species. Our work provides empirical support for a resolution to the apparently paradoxical findings that rare species experience stronger CNDD and may help reconcile contrasting findings for the relationship between the CNDD strength and abundance.

Prevalence of persistent central-involved diabetic macular edema (DME) through 24 weeks of anti-vascular endothelial growth factor therapy and its longer-term outcomes may be relevant to treatment. OBJECTIVE To assess outcomes of DME persisting at least 24 weeks after randomization to treatment with 2.0-mg aflibercept, 1.25-mg bevacizumab, or 0.3-mg ranibizumab. DESIGN, SETTING, AND PARTICIPANTS Post hoc analyses of a clinical trial, the DRCR.net Protocol T among 546 of 660 participants (82.7%) meeting inclusion criteria for this investigation. INTERVENTIONS Six monthly intravitreous anti-vascular endothelial growth factor injections (unless success after 3 to 5 injections); subsequent injections or focal/grid laser as needed per protocol to achieve stability. MAIN OUTCOMES AND MEASURES Persistent DME through 24 weeks, probability of chronic persistent DME through 2 years, and at least 10-letter (Ն 2-line) gain or loss of visual acuity. RESULTS The mean age of participants was 60 years, 363 (66.5%) were white, and 251 (46.0%) were women. Persistent DME through 24 weeks was more frequent with bevacizumab (118 of 180 [65.6%]) than aflibercept (60 of 190 [31.6%]) or ranibizumab (73 of 176 [41.5%]) (aflibercept vs bevacizumab, P < .001; ranibizumab vs bevacizumab, P < .001; and aflibercept vs ranibizumab, P = .05). Among eyes with persistent DME through 24 weeks (n = 251), rates of chronic persistent DME through 2 years were 44.2% with aflibercept, 68.2% with bevacizumab (aflibercept vs bevacizumab, P = .03), and 54.5% with ranibizumab (aflibercept vs ranibizumab, P = .41; bevacizumab vs ranibizumab, P = .16). Among eyes with persistent DME through 24 weeks, proportions with vs without chronic persistent DME through 2 years gaining at least 10 letters from baseline were 62% of 29 eyes vs 63% of 30 eyes (P = .88) with aflibercept, 51% of 70 vs 55% of 31 (P = .96) with bevacizumab, and 45% of 38 vs 66% of 29 (P = .10) with ranibizumab. Only 3 eyes with chronic persistent DME lost at least 10 letters. CONCLUSIONS AND RELEVANCE Persistent DME was more likely with bevacizumab than with aflibercept or ranibizumab. Among eyes with persistent DME, eyes assigned to bevacizumab were more likely to have chronic persistent DME than eyes assigned to aflibercept. These results suggest meaningful gains in vision with little risk of vision loss, regardless of anti-vascular endothelial growth factor agent given or persistence of DME through 2 years. Caution is warranted when considering switching therapies for persistent DME following 3 or more injections; improvements could be owing to continued treatment rather than switching therapies. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT011627249

; for the DRCR Retina Network IMPORTANCE Intravitreous injections of antivascular endothelial growth factor agents are effective for treating diabetic macular edema (DME) involving the center of the macula (center-involved DME [CI-DME]) with visual acuity impairment (20/32 or worse). The best approach to treating patients with CI-DME and good visual acuity (20/25 or better) is unknown. OBJECTIVE To compare vision loss at 2 years among eyes initially managed with aflibercept, laser photocoagulation, or observation. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial conducted at 91 US and Canadian sites among 702 adults with type 1 or type 2 diabetes. Participants had 1 study eye with CI-DME and visual acuity of 20/25 or better. The first participant was randomized on November 8, 2013, and the final date of follow-up was September 11, 2018. INTERVENTIONS Eyes were randomly assigned to 2.0 mg of intravitreous aflibercept (n = 226) as frequently as every 4 weeks, focal/grid laser photocoagulation (n = 240), or observation (n = 236). Aflibercept was required for eyes in the laser photocoagulation or observation groups that had decreased visual acuity from baseline by at least 10 letters (Ն 2 lines on an eye chart) at any visit or by 5 to 9 letters (1-2 lines) at 2 consecutive visits. MAIN OUTCOMES AND MEASURES The primary outcome was at least a 5-letter visual acuity decrease from baseline at 2 years. Antiplatelet Trialists' Collaboration adverse events (defined as myocardial infarction, stroke, or vascular or unknown death) were reported. RESULTS Among 702 randomized participants (mean age, 59 years; 38% female [n=264]), 625 of 681 (92% excluding deaths) completed the 2-year visit. For eyes with visual acuity that decreased from baseline, aflibercept was initiated in 25% (60/240) and 34% (80/236) in the laser photocoagulation and observation groups, respectively. At 2 years, the percentage of eyes with at least a 5-letter visual acuity decrease was 16% (33/205), 17% (36/212), and 19% (39/208

Summary1. Plants form mutualistic symbioses with a variety of microorganisms including endophytic fungi that live inside the plant and cause no overt symptoms of infection. Some endophytic fungi form defensive mutualisms based on the production of bioactive metabolites that protect the plant from herbivores in exchange for a protected niche and nutrition from the host plant. Key elements of these symbioses are vertical transmission of the fungus through seed of the host plant, a narrow host range, and production of bioactive metabolites by the fungus. 2. Grasses frequently form symbioses with endophytic fungi belonging to the family Clavicipitaceae. These symbioses have been studied extensively because of their significant impacts on insect and mammalian herbivores. Many of the impacts are likely due to the production of four classes of bioactive alkaloids -ergot alkaloids, lolines, indole-diterpenes and peraminethat are distributed in different combinations among endophyte taxa. 3. Several legumes, including locoweeds, are associated with a toxic syndrome called locoism as a result of their accumulation of swainsonine. Species in two genera were recently found to contain previously undescribed endophytic fungi (Undifilum spp., family Pleosporaceae) that are the source of that toxin. The fungi are strictly vertically transmitted and have narrow host ranges. 4. Some plant species in the morning glory family (Convolvulaceae) also form symbioses with endophytic fungi of the Clavicipitaceae that produce ergot alkaloids and, perhaps in at least one case, lolines. Other species in this plant family form symbioses with undescribed fungi that produce swainsonine. The swainsonine-producing endophytes associated with the Convolvulaceae are distinct from the Undifilum spp. associated with locoweeds and the Clavicipitaceous fungi associated with Convolvulaceae. 5. In the establishment of vertically transmitted symbioses, fungi must have entered the symbiosis with traits that were immediately useful to the plant. Bioactive metabolites are likely candidates for such pre-adapted traits which were likely useful to the free-living fungi as well. With future research, vertically transmitted fungi from diverse clades with narrow host ranges and that produce bioactive compounds are likely to be found as important mutualists in additional plants.

Animal propulsors such as wings and fins bend during motion and these bending patterns are believed to contribute to the high efficiency of animal movements compared with those of man-made designs. However, efforts to implement flexible designs have been met with contradictory performance results. Consequently, there is no clear understanding of the role played by propulsor flexibility or, more fundamentally, how flexible propulsors should be designed for optimal performance. Here we demonstrate that during steady-state motion by a wide range of animals, from fruit flies to humpback whales, operating in either air or water, natural propulsors bend in similar ways within a highly predictable range of characteristic motions. By providing empirical design criteria derived from natural propulsors that have convergently arrived at a limited design space, these results provide a new framework from which to understand and design flexible propulsors.