Fitness benefits of prolonged post-reproductive lifespan in women

Most animals reproduce until they die, but in humans, females can survive long after ceasing reproduction. In theory, a prolonged post-reproductive lifespan will evolve when females can gain greater fitness by increasing the success of their offspring than by continuing to breed themselves. Although reproductive success is known to decline in old age, it is unknown whether women gain fitness by prolonging lifespan post-reproduction. Using complete multi-generational demographic records, we show that women with a prolonged post-reproductive lifespan have more grandchildren, and hence greater fitness, in pre-modern populations of both Finns and Canadians. This fitness benefit arises because post-reproductive mothers enhance the lifetime reproductive success of their offspring by allowing them to breed earlier, more frequently and more successfully. Finally, the fitness benefits of prolonged lifespan diminish as the reproductive output of offspring declines. This suggests that in female humans, selection for deferred ageing should wane when one's own offspring become post-reproductive and, correspondingly, we show that rates of female mortality accelerate as their offspring terminate reproduction

A randomized, phase III trial to evaluate rucaparib monotherapy as maintenance treatment in patients with newly diagnosed ovarian cancer (ATHENA–MONO/GOG-3020/ENGOT-ov45)

PURPOSE: ATHENA (ClinicalTrials.gov identifier: NCT03522246) was designed to evaluate rucaparib first-line maintenance treatment in a broad patient population, including those without BRCA1 or BRCA2 (BRCA) mutations or other evidence of homologous recombination deficiency (HRD), or high-risk clinical characteristics such as residual disease. We report the results from the ATHENA–MONO comparison of rucaparib versus placebo. METHODS: Patients with stage III-IV high-grade ovarian cancer undergoing surgical cytoreduction (R0/complete resection permitted) and responding to first-line platinum-doublet chemotherapy were randomly assigned 4:1 to oral rucaparib 600 mg twice a day or placebo. Stratification factors were HRD test status, residual disease after chemotherapy, and timing of surgery. The primary end point of investigator-assessed progression-free survival was assessed in a step-down procedure, first in the HRD population (BRCA-mutant or BRCA wild-type/loss of heterozygosity high tumor), and then in the intent-to-treat population. RESULTS: As of March 23, 2022 (data cutoff), 427 and 111 patients were randomly assigned to rucaparib or placebo, respectively (HRD population: 185 v 49). Median progression-free survival (95% CI) was 28.7 months (23.0 to not reached) with rucaparib versus 11.3 months (9.1 to 22.1) with placebo in the HRD population (log-rank P = .0004; hazard ratio [HR], 0.47; 95% CI, 0.31 to 0.72); 20.2 months (15.2 to 24.7) versus 9.2 months (8.3 to 12.2) in the intent-to-treat population (log-rank P < .0001; HR, 0.52; 95% CI, 0.40 to 0.68); and 12.1 months (11.1 to 17.7) versus 9.1 months (4.0 to 12.2) in the HRD-negative population (HR, 0.65; 95% CI, 0.45 to 0.95). The most common grade ≥ 3 treatment-emergent adverse events were anemia (rucaparib, 28.7% v placebo, 0%) and neutropenia (14.6% v 0.9%). CONCLUSION: Rucaparib monotherapy is effective as first-line maintenance, conferring significant benefit versus placebo in patients with advanced ovarian cancer with and without HRD

An Integrated Approach for the Analysis of Biological Pathways using Mixed Models

Gene class, ontology, or pathway testing analysis has become increasingly popular in microarray data analysis. Such approaches allow the integration of gene annotation databases, such as Gene Ontology and KEGG Pathway, to formally test for subtle but coordinated changes at a system level. Higher power in gene class testing is gained by combining weak signals from a number of individual genes in each pathway. We propose an alternative approach for gene-class testing based on mixed models, a class of statistical models that

Haul-Out Behavior of Harbor Seals (Phoca vitulina) in Hood Canal, Washington

The goal of this study was to model haul-out behavior of harbor seals (Phoca vitulina) in the Hood Canal region of Washington State with respect to changes in physiological, environmental, and temporal covariates. Previous research has provided a solid understanding of seal haul-out behavior. Here, we expand on that work using a generalized linear mixed model (GLMM) with temporal autocorrelation and a large dataset. Our dataset included behavioral haul-out records from archival and VHF radio tag deployments on 25 individual seals representing 61,430 seal hours. A novel application for increased computational efficiency allowed us to examine this large dataset with a GLMM that appropriately accounts for temporal autocorellation. We found significant relationships with the covariates hour of day, day of year, minutes from high tide and year. Additionally, there was a significant effect of the interaction term hour of day : day of year. This interaction term demonstrated that seals are more likely to haul out during nighttime hours in August and September, but then switch to predominantly daylight haul-out patterns in October and November. We attribute this change in behavior to an effect of human disturbance levels. This study also examined a unique ecological event to determine the role of increased killer whale (Orcinus orca) predation on haul-out behavior. In 2003 and 2005 these harbor seals were exposed to unprecedented levels of killer whale predation and results show an overall increase in haul-out probability after exposure to killer whales. The outcome of this study will be integral to understanding any changes in population abundance as a result of increased killer whale predation

Childhood body mass index trajectories: modeling, characterizing, pairwise correlations and socio-demographic predictors of trajectory characteristics

Background: Modeling childhood body mass index (BMI) trajectories, versus estimating change in BMI between specific ages, may improve prediction of later body-size-related outcomes. Prior studies of BMI trajectories are limited by restricted age periods and insufficient use of trajectory information. Methods: Among 3,289 children seen at 81,550 pediatric well-child visits from infancy to 18 years between 1980 and 2008, we fit individual BMI trajectories using mixed effect models with fractional polynomial functions. From each child's fitted trajectory, we estimated age and BMI at infancy peak and adiposity rebound, and velocity and area under curve between 1 week, infancy peak, adiposity rebound, and 18 years. Results: Among boys, mean (SD) ages at infancy BMI peak and adiposity rebound were 7.2 (0.9) and 49.2 (11.9) months, respectively. Among girls, mean (SD) ages at infancy BMI peak and adiposity rebound were 7.4 (1.1) and 46.8 (11.0) months, respectively. Ages at infancy peak and adiposity rebound were weakly inversely correlated (r = -0.09). BMI at infancy peak and adiposity rebound were positively correlated (r = 0.76). Blacks had earlier adiposity rebound and greater velocity from adiposity rebound to 18 years of age than whites. Higher birth weight z-score predicted earlier adiposity rebound and higher BMI at infancy peak and adiposity rebound. BMI trajectories did not differ by birth year or type of health insurance, after adjusting for other socio-demographics and birth weight z-score. Conclusions: Childhood BMI trajectory characteristics are informative in describing childhood body mass changes and can be estimated conveniently. Future research should evaluate associations of these novel BMI trajectory characteristics with adult outcomes

Behaviourally Mediated Phenotypic Selection in a Disturbed Coral Reef Environment

Natural and anthropogenic disturbances are leading to changes in the nature of many habitats globally, and the magnitude and frequency of these perturbations are predicted to increase under climate change. Globally coral reefs are one of the most vulnerable ecosystems to climate change. Fishes often show relatively rapid declines in abundance when corals become stressed and die, but the processes responsible are largely unknown. This study explored the mechanism by which coral bleaching may influence the levels and selective nature of mortality on a juvenile damselfish, Pomacentrus amboinensis, which associates with hard coral. Recently settled fish had a low propensity to migrate small distances (40 cm) between habitat patches, even when densities were elevated to their natural maximum. Intraspecific interactions and space use differ among three habitats: live hard coral, bleached coral and dead algal-covered coral. Large fish pushed smaller fish further from the shelter of bleached and dead coral thereby exposing smaller fish to higher mortality than experienced on healthy coral. Small recruits suffered higher mortality than large recruits on bleached and dead coral. Mortality was not size selective on live coral. Survival was 3 times as high on live coral as on either bleached or dead coral. Subtle behavioural interactions between fish and their habitats influence the fundamental link between life history stages, the distribution of phenotypic traits in the local population and potentially the evolution of life history strategies

Spatial and temporal patterns of root distribution in developing stands of four woody crop species grown with drip irrigation and fertilization.

Abstract In forest trees, roots mediate such significant carbon fluxes as primary production and soil C02 efflux. Despite the central role of roots in these critical processes, information on root distribution during stand establishment is limited, yet must be described to accurately predict how various forest types, which are growing with a range of resource limitations, might respond to environmental change. This study reports root length density and biomass development in young stands of eastern cottonwood (Populus deltoidies Bartr.) and American sycamore (Platanus occidentalis L.) that have narrow, high resource site requirements, and compares them with sweetgum (Liquidambar styraczj7ua L.) and loblolly pine (Pinus taeda L.), which have more robust site requirements. Fine roots (5 mm) were sampled to determine spatial distribu-tion in response to fertilizer and irrigation treatments delivered through drip irrigation tubes. Root length density and biomass were predominately controlled by stand development, depth and proximity to drip tubes. After accounting for this spatial and temporal variation, there was a significant increase in RLD with fertilization and irrigation for all genotypes. The response to fertilization was greater than that of irrigation. Both fine and coarse roots responded positively to resources delivered through the drip tube, indicating a wholeroot- system response to resource enrichment and not just a feeder root response. The plastic response to drip tube water and nutrient enrichment demonstmte the capability of root systems to respond to supply heterogeneity by increasing acquisition surface. Fineroot biomass, root density and specific root length were greater for broadleaved species than pine. Roots of all genotypes explored the rooting volume within 2 years, but this occurred faster and to higher root length densities in broadleaved species, indicating they had greater initial opportunity for resource acquisition than pine. Sweetgum's root characteristics and its response to resource availability were similar to the other broadleaved species, despite its hnctional resemblance to pine regarding robust site requirements. It was concluded that genotypes, irrigation arid fertilization significantly influenced tree root system development, which varied spatially in response to resource-supply heterogeneity created by dnp tubes. Knowledge of spatial and temporal patterns of root distribution in these stands will be used to interpret nutrient acquisition and soil respiration measurements