Proof of Concept to Clinical Confirmation: Evolving Clinical Trial Designs for Targeted Agents

No single therapy benefits the majority of patients in the practice of oncology as responses differ even among patients with similar tumor types. The variety of response to therapy witnessed while treating our patients supports the concept of personalized medicine using patients' genomic and biologic information and their clinical characteristics to make informed decisions about their treatment. Personalized medicine relies on identification and confirmation of biologic targets and development of agents to target them. These targeted agents tend to focus on subsets of patients and provide improved clinical outcomes. The continued success of personalized medicine will depend on the expedited development of new agents from proof of concept to confirmation of clinical efficacy

The agrodiversity experiment

Intensively managed grasslands are globally prominent ecosystems. We investigated whether experimental increases in plant diversity in intensively managed grassland communities can increase their resource use efficiency. This work consisted of a coordinated, continental-scale 33-site experiment. The core design was 30 plots, representing 15 grassland communities at two seeding densities. The 15 communities comprised four monocultures (two grasses and two legumes) and 11 four-species mixtures that varied in the relative abundance of the four species at sowing. There were 1028 plots in the core experiment, with another 572 plots sown for additional treatments. Sites followed a protocol and employed the same experimental methods with certain plot management factors, such as seeding rates and number of cuts, determined by local practice. The four species used at a site depended on geographical location, but the species were chosen according to four functional traits: a fast-establishing grass, a slow-establishing persistent grass, a fast-establishing legume, and a slow-establishing persistent legume. As the objective was to maximize yield for intensive grassland production, the species chosen were all highyielding agronomic species. The data set contains species-specific biomass measurements (yield per species and of weeds) for all harvests for up to four years at 33 sites. Samples of harvested vegetation were also analyzed for forage quality at 26 sites. These data should be of interest to ecologists studying relationships between diversity and ecosystem function and to agronomists interested in sustainable intensification. The large spatial scale of the sites provides opportunity for analyses across spatial (and temporal) scales. The database can also complement existing databases and meta-analyses on biodiversity– ecosystem function relationships in natural communities by focusing on those same relationships within intensively managed agricultural grasslands

The complexities of female mate choice and male polymorphisms: Elucidating the role of genetics, age, and mate-choice copying

Genetic, life history, and environmental factors dictate patterns of variation in sexual traits within and across populations, and thus the action and outcome of sexual selection. This study explores patterns of inheritance, diet, age, and mate-choice copying on the expression of male sexual signals and associated female mate choice in a phenotypically diverse group of Schizocosa wolf spiders. Focal spiders exhibit one of two male phenotypes: ‘ornamented’ males possess large black brushes on their forelegs, and ‘non-ornamented’ males possess no brushes. Using a quantitative genetics breeding design in a mixed population of ornamented/non-ornamented males, we found a strong genetic basis to male phenotype and female choice. We also found that some ornamented males produced some sons with large brushes and others with barely visible brushes. Results of diet manipulations and behavioral mating trials showed no influence of diet on male phenotype or female mate choice. Age post maturation, however, influenced mate choice, with younger females being more likely to mate with ornamented males. A mate-choice copying experiment found that, following observations of another female’s mate choice/copulation, virgin mature females tended to match the mate choice (ornamented vs. non-ornamented males) of the females they observed. Finally, analyses of genetic variation across phenotypically pure (only one male phenotype present) vs. mixed (both phenotypes present) populations revealed genetic distinction between phenotypes in phenotypically-pure populations, but no distinction in phenotypically-mixed populations. The difference in patterns of genetic differentiation and mating across geographic locations suggests a complex network of factors contributing to the outcome of sexual selection

Effects of multi-species swards on dry matter production and the incidence of unsown species at three Irish sites

Recent ecological research provides evidence that an increased number of plant species in natural grasslands is associated with increased biomass productivity, and provides a wide range of other ecosystem benefits. This suggests that increases in species diversity in agricultural ecosystems may similarly lead to increased benefits. The work reported below was part of the COST 852 Agrodiversity experiment, carried out at 34 sites across Europe. In Ireland, the effects of four-species grass-clover mixtures on herbage production, species persistence and unsown species suppression at three sites over multiple years, were investigated under growing conditions that were intensive relative to unfertilised natural grassland systems. The design included a range of four-species mixtures and monocultures of perennial ryegrass, timothy, cocksfoot, white clover, red clover and Caucasian clover. Several harvests were taken at each site for two or three years. Species diversity had a strong, persistent and positive effect on overall yield and the yield of sown species, and enhanced resistance to the growth of unsown species. Mixtures generally yielded well when compared with the best monoculture, and sometimes out yielded it. These effects on total yield declined over time but were still important at the end of the experiments. The diversity effects on sown species yield and on resistance to unsown species increased with time. Diversity effects were robust to changes in species composition, and persisted for the duration of the experiments across mixtures and over time. Virtually every mixture had a higher yield, and suppressed unsown species better, than monocultures of perennial ryegrass. These patterns were broadly consistent across sites. The persistence of species varied widely and was not consistent across sites

The complexities of female mate choice and male polymorphisms: Elucidating the role of genetics, age, and mate-choice copying

Genetic, life history, and environmental factors dictate patterns of variation in sexual traits within and across populations, and thus the action and outcome of sexual selection. This study explores patterns of inheritance, diet, age, and mate-choice copying on the expression of male sexual signals and associated female mate choice in a phenotypically diverse group of Schizocosa wolf spiders. Focal spiders exhibit one of two male phenotypes: ‘ornamented’ males possess large black brushes on their forelegs, and ‘non-ornamented’ males possess no brushes. Using a quantitative genetics breeding design in a mixed population of ornamented/non-ornamented males, we found a strong genetic basis to male phenotype and female choice. We also found that some ornamented males produced some sons with large brushes and others with barely visible brushes. Results of diet manipulations and behavioral mating trials showed no influence of diet on male phenotype or female mate choice. Age post maturation, however, influenced mate choice, with younger females being more likely to mate with ornamented males. A mate-choice copying experiment found that, following observations of another female’s mate choice/copulation, virgin mature females tended to match the mate choice (ornamented vs. non-ornamented males) of the females they observed. Finally, analyses of genetic variation across phenotypically pure (only one male phenotype present) vs. mixed (both phenotypes present) populations revealed genetic distinction between phenotypes in phenotypically-pure populations, but no distinction in phenotypically-mixed populations. The difference in patterns of genetic differentiation and mating across geographic locations suggests a complex network of factors contributing to the outcome of sexual selection

Adapt On-the-Go: Behavior Modulation for Single-Life Robot Deployment

To succeed in the real world, robots must cope with situations that differ from those seen during training. We study the problem of adapting on-the-fly to such novel scenarios during deployment, by drawing upon a diverse repertoire of previously learned behaviors. Our approach, RObust Autonomous Modulation (ROAM), introduces a mechanism based on the perceived value of pre-trained behaviors to select and adapt pre-trained behaviors to the situation at hand. Crucially, this adaptation process all happens within a single episode at test time, without any human supervision. We provide theoretical analysis of our selection mechanism and demonstrate that ROAM enables a robot to adapt rapidly to changes in dynamics both in simulation and on a real Go1 quadruped, even successfully moving forward with roller skates on its feet. Our approach adapts over 2x as efficiently compared to existing methods when facing a variety of out-of-distribution situations during deployment by effectively choosing and adapting relevant behaviors on-the-fly.Comment: 19 pages, 6 figure