Root traits as drivers of plant and ecosystem functioning: current understanding, pitfalls and future research needs.

The effects of plants on the biosphere, atmosphere and geosphere are key determinants of terrestrial ecosystem functioning. However, despite substantial progress made regarding plant belowground components, we are still only beginning to explore the complex relationships between root traits and functions. Drawing on the literature in plant physiology, ecophysiology, ecology, agronomy and soil science, we reviewed 24 aspects of plant and ecosystem functioning and their relationships with a number of root system traits, including aspects of architecture, physiology, morphology, anatomy, chemistry, biomechanics and biotic interactions. Based on this assessment, we critically evaluated the current strengths and gaps in our knowledge, and identify future research challenges in the field of root ecology. Most importantly, we found that belowground traits with the broadest importance in plant and ecosystem functioning are not those most commonly measured. Also, the estimation of trait relative importance for functioning requires us to consider a more comprehensive range of functionally relevant traits from a diverse range of species, across environments and over time series. We also advocate that establishing causal hierarchical links among root traits will provide a hypothesis-based framework to identify the most parsimonious sets of traits with the strongest links on functions, and to link genotypes to plant and ecosystem functioning.

Abiraterone acetate plus prednisone for the Management of Metastatic Castration-Resistant Prostate Cancer (mCRPC) without prior use of chemotherapy: report from a large, international, real-world retrospective cohort study.

BACKGROUND: With the recent introduction of novel treatment options, real-world data from patients with metastatic castration-resistant prostate cancer (mCRPC) are required to better understand the impact on routine clinical practice. This study primarily aimed to describe the time to treatment failure (TTF) of mCRPC patients treated with abiraterone acetate plus prednisone or the corticosteroid of choice (AAP) in the pre-chemotherapy setting. Other relevant outcomes, clinical and treatment characteristics of these patients were also evaluated. METHODS: This retrospective, observational study collected data from chemotherapy-naïve mCRPC patients treated with AAP from four European countries. Kaplan-Meier curves were used to estimate TTF, progression-free survival (PFS), and time to first skeletal-related event. The impact of baseline characteristics on TTF and PFS was explored using univariate and multivariate Cox proportional hazard models. Log-rank test was used to assess the potential role of duration of response to ADT in predicting response to AAP treatment. RESULTS: Data from 481 eligible patients (Belgium: 68; France: 61; Germany: 150; UK: 202) were analysed. At AAP initiation, the median age of patients was 75.0 years (interquartile range [IQR]: 69.0-81.0), and the median PSA was 56.2 ng/mL (IQR: 22.2-133.1), with over 50% of patients presenting an ECOG score of 0 or 1. Visceral metastases were present in 7.5% of patients; an exclusion criterion in the COU-AA-302 clinical trial. The median TTF with AAP was 10.0 months (95%CI: 9.2-11.1) and the median PFS was 10.8 months (95%CI: 9.6-11.8). Shorter TTF was significantly associated with higher ALP (> 119 units/L), higher PSA (> 56.2 ng/mL), or poorer ECOG PS scores at AAP initiation (p < 0.05). Patients with longer duration of response to ADT (≥12 months) presented longer TTF and longer time to progression (p < 0.0001). CONCLUSIONS: This European real-world study provides valuable insights into the characteristics, treatment, and outcomes of chemotherapy-naïve patients with mCRPC who received AAP in routine clinical practice. Treatment effectiveness of AAP in the real-world is maintained despite patients having poorer clinical features at initiation than those observed in the COU-AA-302 trial population.

Adaptive root foraging strategies along a boreal-temperate forest gradient.

The tree root-mycorhizosphere plays a key role in resource uptake, but also in the adaptation of forests to changing environments. The adaptive foraging mechanisms of ectomycorrhizal (EcM) and fine roots of Picea abies, Pinus sylvestris and Betula pendula were evaluated along a gradient from temperate to subarctic boreal forest (38 sites between latitudes 48°N and 69°N) in Europe. Variables describing tree resource uptake structures and processes (absorptive fine root biomass and morphology, nitrogen (N) concentration in absorptive roots, extramatrical mycelium (EMM) biomass, community structure of root-associated EcM fungi, soil and rhizosphere bacteria) were used to analyse relationships between root system functional traits and climate, soil and stand characteristics. Absorptive fine root biomass per stand basal area increased significantly from temperate to boreal forests, coinciding with longer and thinner root tips with higher tissue density, smaller EMM biomass per root length and a shift in soil microbial community structure. The soil carbon (C) : N ratio was found to explain most of the variability in absorptive fine root and EMM biomass, root tissue density, N concentration and rhizosphere bacterial community structure. We suggest a concept of absorptive fine root foraging strategies involving both qualitative and quantitative changes in the root-mycorrhiza-bacteria continuum along climate and soil C : N gradients.

Quantifying rooting at depth in a wheat doubled haploid population with introgression from wild emmer.

Background and Aims: The genetic basis of increased rooting below the plough layer, post-anthesis in the field, of an elite wheat line (Triticum aestivum 'Shamrock') with recent introgression from wild emmer (T. dicoccoides), is investigated. Shamrock has a non-glaucous canopy phenotype mapped to the short arm of chromosome 2B (2BS), derived from the wild emmer. A secondary aim was to determine whether genetic effects found in the field could have been predicted by other assessment methods. Methods: Roots of doubled haploid (DH) lines from a winter wheat ('Shamrock' × 'Shango') population were assessed using a seedling screen in moist paper rolls, in rhizotrons to the end of tillering, and in the field post-anthesis. A linkage map was produced using single nucleotide polymorphism markers to identify quantitative trait loci (QTLs) for rooting traits. Key Results: Shamrock had greater root length density (RLD) at depth than Shango, in the field and within the rhizotrons. The DH population exhibited diversity for rooting traits within the three environments studied. QTLs were identified on chromosomes 5D, 6B and 7B, explaining variation in RLD post-anthesis in the field. Effects associated with the non-glaucous trait on RLD interacted significantly with depth in the field, and some of this interaction mapped to 2BS. The effect of genotype was strongly influenced by the method of root assessment, e.g. glaucousness expressed in the field was negatively associated with root length in the rhizotrons, but positively associated with length in the seedling screen. Conclusions: To our knowledge, this is the first study to identify QTLs for rooting at depth in field-grown wheat at mature growth stages. Within the population studied here, our results are consistent with the hypothesis that some of the variation in rooting is associated with recent introgression from wild emmer. The expression of genetic effects differed between the methods of root assessment.

Insect pollination reduces yield loss following heat stress in faba bean (Vicia faba L.).

Global food security, particularly crop fertilization and yield production, is threatened by heat waves that are projected to increase in frequency and magnitude with climate change. Effects of heat stress on the fertilization of insect-pollinated plants are not well understood, but experiments conducted primarily in self-pollinated crops, such as wheat, show that transfer of fertile pollen may recover yield following stress. We hypothesized that in the partially pollinator-dependent crop, faba bean (Vicia faba L.), insect pollination would elicit similar yield recovery following heat stress. We exposed potted faba bean plants to heat stress for 5 days during floral development and anthesis. Temperature treatments were representative of heat waves projected in the UK for the period 2021-2050 and onwards. Following temperature treatments, plants were distributed in flight cages and either pollinated by domesticated Bombus terrestris colonies or received no insect pollination. Yield loss due to heat stress at 30 °C was greater in plants excluded from pollinators (15%) compared to those with bumblebee pollination (2.5%). Thus, the pollinator dependency of faba bean yield was 16% at control temperatures (18-26 °C) and extreme stress (34 °C), but was 53% following intermediate heat stress at 30 °C. These findings provide the first evidence that the pollinator dependency of crops can be modified by heat stress, and suggest that insect pollination may become more important in crop production as the probability of heat waves increases.

Elevated CO2 enrichment induces a differential biomass response in a mixed species temperate forest plantation.

In a free-air carbon dioxide (CO(2)) enrichment study (BangorFACE), Alnus glutinosa, Betula pendula and Fagus sylvatica were planted in areas of one-, two- and three-species mixtures (n = 4). The trees were exposed to ambient or elevated CO(2) (580 µmol mol(-1)) for 4 yr, and aboveground growth characteristics were measured. In monoculture, the mean effect of CO(2) enrichment on aboveground woody biomass was + 29, + 22 and + 16% for A. glutinosa, F. sylvatica and B. pendula, respectively. When the same species were grown in polyculture, the response to CO(2) switched to + 10, + 7 and 0% for A. glutinosa, B. pendula and F. sylvatica, respectively. In ambient atmosphere, our species grown in polyculture increased aboveground woody biomass from 12.9 ± 1.4 to 18.9 ± 1.0 kg m(-2), whereas, in an elevated CO(2) atmosphere, aboveground woody biomass increased from 15.2 ± 0.6 to 20.2 ± 0.6 kg m(-2). The overyielding effect of polyculture was smaller (+ 7%) in elevated CO(2) than in an ambient atmosphere (+ 18%). Our results show that the aboveground response to elevated CO(2) is affected significantly by intra- and interspecific competition, and that the elevated CO(2) response may be reduced in forest communities comprising tree species with contrasting functional traits.

Fragment size and diversity of mulches affect their decomposition, nutrient dynamics, and mycorrhizal root colonisation.

Plant-based mulch has been proposed as a sustainable way of maintaining soil fertility. However, the role of mulch diversity, quality, and size in decomposition dynamics, and their effect on crop yield, has not been fully explored. We investigated how mulch quality, proxied by the constituent plant species diversity, and residue size drive mulch decomposition, nutrient release, crop nutrition, and yield. A rhizotron experiment was set up with barley as a model crop, with the addition of mulch of two particle sizes (1.5 and 30 cm) and four different plant residue mixes of differing biodiversity (17, 12, 6, and 1 species) in a fully factorial design. Soil nutrient dynamics were measured at advanced decomposition stages, together with residue quality, arbuscular mycorrhizal fungal (AMF) root colonisation, and crop yield. Residue mass loss was significantly affected by its chemical composition. Initial NDF content was more restricted factor in C and N mineralisation than C:N or lignin. Long residues retained significantly higher C and N content, than short residues. Crop yield was not affected by residue type or size. Residue size significantly affected barley growth rate, influencing seed protein content. Soil available K was significantly increased by residues with a higher initial C:N ratio. Short residues resulted in higher soil Zn. Residues of higher diversity resulted inhigher AMF root colonisationof the barley plants. Generally, long residue mulches maintain higher fertilisation capacity at advanced stage of decomposition than short ones, without a deleterious effect on crop yield. Further investigation should evaluate the effect of continuous application of long residue mulches on soil fertility and microbial symbiosis.

Study on emotion recognition bias in different regional groups.

Human-machine communication can be substantially enhanced by the inclusion of high-quality real-time recognition of spontaneous human emotional expressions. However, successful recognition of such expressions can be negatively impacted by factors such as sudden variations of lighting, or intentional obfuscation. Reliable recognition can be more substantively impeded due to the observation that the presentation and meaning of emotional expressions can vary significantly based on the culture of the expressor and the environment within which the emotions are expressed. As an example, an emotion recognition model trained on a regionally-specific database collected from North America might fail to recognize standard emotional expressions from another region, such as East Asia. To address the problem of regional and cultural bias in emotion recognition from facial expressions, we propose a meta-model that fuses multiple emotional cues and features. The proposed approach integrates image features, action level units, micro-expressions and macro-expressions into a multi-cues emotion model (MCAM). Each of the facial attributes incorporated into the model represents a specific category: fine-grained content-independent features, facial muscle movements, short-term facial expressions and high-level facial expressions. The results of the proposed meta-classifier (MCAM) approach show that a) the successful classification of regional facial expressions is based on non-sympathetic features b) learning the emotional facial expressions of some regional groups can confound the successful recognition of emotional expressions of other regional groups unless it is done from scratch and c) the identification of certain facial cues and features of the data-sets that serve to preclude the design of the perfect unbiased classifier. As a result of these observations we posit that to learn certain regional emotional expressions, other regional expressions first have to be "forgotten".

Asynchronous flowering and within-plant flowering diversity in wheat and the implications for crop resilience to heat.

BACKGROUND AND AIMS: Self-pollination dominates in wheat, with a small level of out-crossing due to flowering asynchrony and male sterility. However, the timing and synchrony of male and female flowering in wheat is a crucial determinant of seed set and may be an important factor affecting gene flow and resilience to climate change. Here, a methodology is presented for assessing the timing and synchrony of flowering in wheat, Triticum aestivum. METHODS: From the onset of flowering until the end of anthesis, the anther and stigma activity of each floret was assessed on the first five developing ears in potted plants grown under ambient conditions and originating from 'Paragon' or 'Spark-Rialto' backgrounds. At harvest maturity, seed presence, size and weight was recorded for each floret scored. KEY RESULTS AND CONCLUSIONS: The synchrony between pollen dehiscence and stigma collapse within a flower was dependent on its relative position in a spike and within a floret. Determined on the basis of synchrony within each flower, the level of pollination by pollen originating from other flowers reached approx. 30 % and did not change throughout the duration of flowering. A modelling exercise parameterized by flowering observations indicated that the temporal and spatial variability of anther activity within and between spikes may influence the relative resilience of wheat to sudden, extreme climatic events which has direct relevance to predicted future climate scenarios in the UK.

Toward a function-first framework to make soil microbial ecology predictive.

Soil microbial communities perform vital ecosystem functions, such as the decomposition of organic matter to provide plant nutrition. However, despite the functional importance of soil microorganisms, attribution of ecosystem function to particular constituents of the microbial community has been impeded by a lack of information linking microbial function to community composition and structure. Here, we propose a function-first framework to predict how microbial communities influence ecosystem functions. We first view the microbial community associated with a specific function as a whole and describe the dependence of microbial functions on environmental factors (e.g., the intrinsic temperature dependence of bacterial growth rates). This step defines the aggregate functional response curve of the community. Second, the contribution of the whole community to ecosystem function can be predicted, by combining the functional response curve with current environmental conditions. Functional response curves can then be linked with taxonomic data in order to identify sets of "biomarker" taxa that signal how microbial communities regulate ecosystem functions. Ultimately, such indicator taxa may be used as a diagnostic tool, enabling predictions of ecosystem function from community composition. In this paper, we provide three examples to illustrate the proposed framework, whereby the dependence of bacterial growth on environmental factors, including temperature, pH, and salinity, is defined as the functional response curve used to interlink soil bacterial community structure and function. Applying this framework will make it possible to predict ecosystem functions directly from microbial community composition.

Real-world Treatment Sequencing in Patients with Metastatic Castration-resistant Prostate Cancer: Results from the Prospective, International, Observational Prostate Cancer Registry.

Background: Prostate cancer has a multifaceted treatment pattern. Evidence is lacking for optimal treatment sequences for metastatic castration-resistant prostate cancer (mCRPC). Objective: To increase the understanding of real-world treatment pathways and outcomes in patients with mCRPC. Design setting and participants: A prospective, noninterventional, real-world analysis of 3003 patients with mCRPC in the Prostate Cancer Registry (PCR; NCT02236637) from June 14, 2013 to July 9, 2018 was conducted. Intervention: Patients received first- and second-line hormonal treatment and chemotherapy as follows: abiraterone acetate plus prednisone (abiraterone)-docetaxel (ABI-DOCE), abiraterone-enzalutamide (ABI-ENZA), abiraterone-radium-223 (ABI-RAD), docetaxel-abiraterone (DOCE-ABI), docetaxel-cabazitaxel (DOCE-CABA), docetaxel-enzalutamide (DOCE-ENZA), and enzalutamide-docetaxel (ENZA-DOCE). Outcome measurements and statistical analysis: Baseline patient characteristics, quality of life, mCRPC treatments, and efficacy outcomes (progression and survival) were presented descriptively. Results and limitations: Data from 727 patients were eligible for the analysis (ABI-DOCE n = 178, ABI-ENZA n = 99, ABI-RAD n = 27, DOCE-ABI n = 191, DOCE-CABA n = 74, DOCE-ENZA n = 116, and ENZA-DOCE n = 42). Demographics and disease characteristics among patients between different sequences varied greatly. Most patients who started on abiraterone or enzalutamide stopped therapy because of disease progression. No randomisation to allow treatment/sequence comparisons limited this observational study. Conclusions: The real-world PCR data complement clinical trial data, reflecting more highly selected patient populations than seen in routine clinical practice. Baseline characteristics play a role in mCRPC first-line treatment selection, but other factors, such as treatment availability, have an impact. Efficacy observations are limited and should be interpreted with caution. Patient summary: Baseline characteristics appear to have a role in the first-line treatment selection of metastatic castration-resistant prostate cancer in the real-world setting. First-line abiraterone acetate plus prednisone seems to be the preferred treatment option for older patients and those with lower Gleason scores, first-line docetaxel for younger patients and those with more advanced disease, and first-line enzalutamide for patients with fewer metastases and more favourable performance status. The benefit to patients from these observations remains unknown.

Competition for soil resources forces a trade-off between enhancing tree productivity and understorey species richness in managed beech forests.

Traditionally focussed on maximising productivity, forest management increasingly has to consider other functions performed by the forest stands, such as biodiversity conservation. Terrestrial plant communities typically possess a hump-back relationship between biomass productivity and plant species richness. However, there is evidence of a reverse relationship in forests dominated by beech, one of the most competitive and widespread tree species in temperate Europe. To fully explore the tree productivity-species richness relationship, we investigated above- and below-ground drivers of understorey plant species richness. We focussed on managed beech forests growing along an elevation gradient in Central Europe. We found that the lowest understorey plant diversity was under conditions optimal for beech. Tree fine root mass, canopy openness, soil C/N ratio, the interaction between tree fine root mass and stoniness, and stand structural diversity explain the variation of understorey species richness. We show that the competition for soil resources is the main driver of plant species diversity in managed forests; maximising beech growth in optimal conditions may thus come at the expense of understorey plant richness.

Fine-scale variation in projected climate change presents opportunities for biodiversity conservation in Europe.

Climate change is a major threat to global biodiversity, although projected changes show remarkable geographical and temporal variability. Understanding this variability allows for the identification of regions where the present-day conservation objectives may be at risk or where opportunities for biodiversity conservation emerge. We use a multi-model ensemble of regional climate models to identify areas with significantly high and low climate stability persistent throughout the twenty-first century in Europe. We then confront our predictions with the land coverage of three prominent biodiversity conservation initiatives at two scales. The continental-scale assessment shows that areas with the least stable future climate in Europe are likely to occur at low and high latitudes, with the Iberian Peninsula and the Boreal zones identified as prominent areas of low climatic stability. A follow-up regional scale investigation shows that robust climatic refugia exist even within the highly exposed southern and northern macro-regions. About 23-31% of assessed biodiversity conservation sites in Europe coincide with areas of high future climate stability, we contend that these sites should be prioritised in the formulation of future conservation priorities as the stability of future climate is one of the key factors determining their conservation prospects. Although such focus on climate refugia cannot halt the ongoing biodiversity loss, along with measures such as resilience-based stewardship, it may improve the effectiveness of biodiversity conservation under climate change.

Real-World Safety and Efficacy Outcomes with Abiraterone Acetate Plus Prednisone or Prednisolone as the First- or Second-Line Treatment for Metastatic Castration-Resistant Prostate Cancer: Data from the Prostate Cancer Registry.

BACKGROUND: Despite standard-of-care androgen-deprivation therapy and an increasing number of treatment options, the mortality rate for prostate cancer remains high. Progress to metastatic castration-resistant prostate cancer (mCRPC) necessitates additional treatments. Abiraterone acetate plus prednisone or prednisolone (AAP) prolongs survival in chemotherapy-naive and docetaxel-experienced patients. OBJECTIVE: To evaluate the real-world safety and efficacy of AAP as first-line and second-line [post-docetaxel only (AAP-PD)] treatment in patients with mCRPC. PATIENTS AND METHODS: The Prostate Cancer Registry (PCR) was a prospective, international, observational study of patients with mCRPC in routine clinical practice. Men aged ≥ 18 years with confirmed mCRPC were included. Baseline characteristics, safety (treatment-emergent adverse events, treatment-emergent severe adverse events), and efficacy [progression-free survival (PFS) and overall survival (OS)] were analyzed. RESULTS: At baseline, patients who received first-line AAP (n = 754) were generally older than patients who received AAP-PD (n = 354); median age was 76 years and 70 years, respectively. However, the rate of visceral metastasis was higher in the AAP-PD cohort than in the AAP cohort (17.7% vs. 9.6%, respectively). Demographics and disease characteristics of patients with baseline cardiovascular disease were similar to those of the overall registry population. Efficacy outcomes were similar for all patients, regardless of the line of AAP therapy. For first-line AAP and AAP-PD, respectively, the median PFS was 8.9 and 5.8 months for all patients and 9.1 and 6.0 months for patients with cardiovascular comorbidities; median OS was 27.1 and 23.4 months for all patients, and 27.4 and 23.1 months for patients with cardiovascular comorbidities. There were no unexpected adverse events in any patient subgroup. CONCLUSIONS: These real-world data complement the findings from randomized controlled trials, indicating that first- and second-line AAP is well tolerated and effective in patients with mCRPC, including those with underlying CV comorbidities. TRIAL REGISTRATION NUMBER: NCT02236637, registered 8 September 2014.

Repurposing potential of posaconazole and grazoprevir as inhibitors of SARS-CoV-2 helicase.

As the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic engulfs millions worldwide, the quest for vaccines or drugs against the virus continues. The helicase protein of SARS-CoV-2 represents an attractive target for drug discovery since inhibition of helicase activity can suppress viral replication. Using in silico approaches, we have identified drugs that interact with SARS-CoV-2 helicase based on the presence of amino acid arrangements matching binding sites of drugs in previously annotated protein structures. The drugs exhibiting an RMSD of ≤ 3.0 Å were further analyzed using molecular docking, molecular dynamics (MD) simulation, and post-MD analyses. Using these approaches, we found 12 drugs that showed strong interactions with SARS-CoV-2 helicase amino acids. The analyses were performed using the recently available SARS-CoV-2 helicase structure (PDB ID: 5RL6). Based on the MM-GBSA approach, out of the 12 drugs, two drugs, namely posaconazole and grazoprevir, showed the most favorable binding energy, - 54.8 and - 49.1 kcal/mol, respectively. Furthermore, of the amino acids found conserved among all human coronaviruses, 10/11 and 10/12 were targeted by, respectively, grazoprevir and posaconazole. These residues are part of the crucial DEAD-like helicase C and DEXXQc_Upf1-like/ DEAD-like helicase domains. Strong interactions of posaconazole and grazoprevir with conserved amino acids indicate that the drugs can be potent against SARS-CoV-2. Since the amino acids are conserved among the human coronaviruses, the virus is unlikely to develop resistance mutations against these drugs. Since these drugs are already in use, they may be immediately repurposed for SARS-CoV-2 therapy.

Global climate change and tree nutrition: effects of elevated CO2 and temperature.

Although tree nutrition has not been the primary focus of large climate change experiments on trees, we are beginning to understand its links to elevated atmospheric CO2 and temperature changes. This review focuses on the major nutrients, namely N and P, and deals with the effects of climate change on the processes that alter their cycling and availability. Current knowledge regarding biotic and abiotic agents of weathering, mobilization and immobilization of these elements will be discussed. To date, controlled environment studies have identified possible effects of climate change on tree nutrition. Only some of these findings, however, were verified in ecosystem scale experiments. Moreover, to be able to predict future effects of climate change on tree nutrition at this scale, we need to progress from studying effects of single factors to analysing interactions between factors such as elevated CO2, temperature or water availability.

Evidence of ecological niche shift in Rhododendron ponticum (L.) in Britain: Hybridization as a possible cause of rapid niche expansion.

Biological invasions threaten global biodiversity and natural resources. Anticipating future invasions is central to strategies for combating the spread of invasive species. Ecological niche models are thus increasingly used to predict potential distribution of invasive species. In this study, we compare ecological niches of Rhododendron ponticum in its native (Iberian Peninsula) and invasive (Britain) ranges. Here, we test the conservation of ecological niche between invasive and native populations of R. ponticum using principal component analysis, niche dynamics analysis, and MaxEnt-based reciprocal niche modeling. We show that niche overlap between native and invasive populations is very low, leading us to the conclusion that the two niches are not equivalent and are dissimilar. We conclude that R. ponticum occupies novel environmental conditions in Britain. However, the evidence of niche shift presented in this study should be treated with caution because of nonanalogue climatic conditions between native and invasive ranges and a small population size in the native range. We then frame our results in the context of contradicting genetic evidence on possible hybridization of this invasive species in Britain. We argue that the existing contradictory studies on whether hybridization caused niche shift in R. ponticum are not sufficient to prove or disprove this hypothesis. However, we present a series of theoretical arguments which indicate that hybridization is a likely cause of the observed niche expansion of R. ponticum in Britain.

Real-World Outcomes in First-Line Treatment of Metastatic Castration-Resistant Prostate Cancer: The Prostate Cancer Registry.

BACKGROUND: Metastatic prostate cancer has a 30% 5-year survival rate despite recent therapeutic advances. There is a need to improve the clinical understanding and treatment of this disease, particularly in the real-world setting and among patients who are under-represented in clinical trials. OBJECTIVE: We aimed to evaluate the characteristics and clinical outcomes of patients who received their first treatment for metastatic castration-resistant prostate cancer (mCRPC) in routine clinical practice, independent of treatment used, including subgroups with baseline cardiac disease, diabetes mellitus, or visceral metastases. PATIENTS AND METHODS: Prospective, noninterventional analysis of patient record data in the multicenter Prostate Cancer Registry (PCR) of men with mCRPC. The data were collected in 16 countries with the aim of recruiting more than 3000 patients between 2013 and 2016. The study end date was 9 July 2018. Data evaluated included baseline characteristics, treatment exposure, and efficacy outcomes [overall survival (OS) and time to progression (TTP)] of patients treated with abiraterone acetate plus prednisone or prednisolone (collectively, "abiraterone"), enzalutamide, or docetaxel. Descriptive outcomes are reported from the overall patient population and subgroups of patients with baseline cardiovascular disease, diabetes mellitus, or visceral metastases. The treatment effects for time to progression were compared for the overall patient population. RESULTS: The study enrollment period lasted 2.5 years, and each patient was followed for a maximum of 3 years. A total of 1874 patients in the PCR had not received previous mCRPC treatment at baseline, although they had received androgen-deprivation therapy. Prevalent co-morbidities included cardiovascular disease in 65.4% and diabetes mellitus in 17.4% of patients. Baseline characteristics suggested that patients with more advanced disease received docetaxel treatment. In the overall patient population, the median time to progression with abiraterone, enzalutamide, and docetaxel as first-line mCRPC therapy was 9.6, 10.3, and 7.6 months, respectively, and median OS was 27.1, 27.1, and 27.9 months, respectively. Outcomes in the subgroups of patients with cardiovascular disease or diabetes mellitus were similar to those of the whole population in the analysis. As expected, patients with visceral metastases had shorter TTP and OS than patients in the overall population. CONCLUSIONS: This analysis shows, for the first time, the effectiveness in parallel of first-line abiraterone, enzalutamide, and docetaxel in mCRPC, including in patients with co-morbidities such as cardiovascular disease or diabetes mellitus or in patients with visceral metastases. These real-world findings from the PCR provide meaningful information to help manage mCRPC, particularly in patients under-represented in clinical studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02236637; registered September 2014.

Impact of Abiraterone Acetate plus Prednisone or Enzalutamide on Patient-reported Outcomes in Patients with Metastatic Castration-resistant Prostate Cancer: Final 12-mo Analysis from the Observational AQUARiUS Study.

BACKGROUND: Few studies have examined patient-reported outcomes (PROs) with abiraterone acetate plus prednisone (abiraterone) versus enzalutamide in metastatic castration-resistant prostate cancer (mCRPC). OBJECTIVE: To determine the impact of abiraterone and enzalutamide on PROs. DESIGN, SETTING, AND PARTICIPANTS: AQUARiUS (NCT02813408) was a prospective, 12-mo, observational study in patients with mCRPC from Denmark, France, and the UK. INTERVENTION: Abiraterone or enzalutamide treatment according to routine practise. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PROs were collected over 12 mo using Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog), Brief Fatigue Inventory-Short Form (BFI-SF), Brief Pain Inventory-Short Form, and European Organisation for Research and Treatment of Cancer-Quality of Life Questionnaire (QLQ-C30) at baseline and routine visits. Outcomes included mean change in PROs, patients with clinically meaningful worsening (CMW) in PROs, and safety. Data were analysed using repeated measures linear and logistic models adjusted for baseline characteristics. RESULTS AND LIMITATIONS: Abiraterone-treated (N = 105) and enzalutamide-treated (N = 106) patients were included. Key PRO items (cognitive impairments and fatigue) were significantly (p < 0.05) in favour of abiraterone versus enzalutamide during the study. "Perceived cognitive impairment" and "comments from others" (FACT-Cog); "fatigue right now", "usual level of fatigue", and "worst level of fatigue" (BFI-SF); and "cognitive functioning" and "fatigue" (QLQ-C30) were significantly in favour of abiraterone over enzalutamide for three or more consecutive periods up to month 12. From study initiation, significantly fewer patients receiving abiraterone experienced one or more CMW episode in cognition and fatigue. Fatigue and asthenia (adverse events) were lower with abiraterone than with enzalutamide (5% vs 15% and 10% vs 11%, respectively). There were no treatment-related deaths. Limitations included lack of randomisation. CONCLUSIONS: In a real-world setting, this 12-mo analysis suggests an advantage of abiraterone acetate plus prednisone over enzalutamide on fatigue and cognitive function; this finding occurred early after treatment initiation. This difference should be considered when choosing treatment. PATIENT SUMMARY: This study looked at the effect of two treatments (abiraterone acetate plus prednisone and enzalutamide) for metastatic castration-resistant prostate cancer on patient quality of life over 12 mo. Using established questionnaires, patients reported that they experienced less fatigue and cognitive impairments (including memory loss and reduced thinking abilities) with abiraterone acetate plus prednisone than with enzalutamide.

Coppicing shifts CO2 stimulation of poplar productivity to above-ground pools: a synthesis of leaf to stand level results from the POP/EUROFACE experiment.

A poplar short rotation coppice (SRC) grown for the production of bioenergy can combine carbon (C) storage with fossil fuel substitution. Here, we summarize the responses of a poplar (Populus) plantation to 6 yr of free air CO(2) enrichment (POP/EUROFACE consisting of two rotation cycles). We show that a poplar plantation growing in nonlimiting light, nutrient and water conditions will significantly increase its productivity in elevated CO(2) concentrations ([CO(2)]). Increased biomass yield resulted from an early growth enhancement and photosynthesis did not acclimate to elevated [CO(2)]. Sufficient nutrient availability, increased nitrogen use efficiency (NUE) and the large sink capacity of poplars contributed to the sustained increase in C uptake over 6 yr. Additional C taken up in high [CO(2)] was mainly invested into woody biomass pools. Coppicing increased yield by 66% and partly shifted the extra C uptake in elevated [CO(2)] to above-ground pools, as fine root biomass declined and its [CO(2)] stimulation disappeared. Mineral soil C increased equally in ambient and elevated [CO(2)] during the 6 yr experiment. However, elevated [CO(2)] increased the stabilization of C in the mineral soil. Increased productivity of a poplar SRC in elevated [CO(2)] may allow shorter rotation cycles, enhancing the viability of SRC for biofuel production.