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2.
Sci Rep ; 13(1): 9383, 2023 06 09.
Article in English | MEDLINE | ID: mdl-37296195

ABSTRACT

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.


Subject(s)
Hordeum , Mycorrhizae , Symbiosis , Biodiversity , Plants/microbiology , Soil/chemistry , Nutrients , Hordeum/metabolism , Soil Microbiology , Plant Roots/metabolism
4.
Sci Rep ; 13(1): 8414, 2023 05 24.
Article in English | MEDLINE | ID: mdl-37225756

ABSTRACT

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".


Subject(s)
Communication , Cues , Humans , Asia, Eastern , Bias , Emotions
5.
Eur Urol Open Sci ; 45: 12-22, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36353661

ABSTRACT

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.

6.
Sci Total Environ ; 849: 157825, 2022 Nov 25.
Article in English | MEDLINE | ID: mdl-35932856

ABSTRACT

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.


Subject(s)
Fagus , Trees , Biodiversity , Forests , Soil/chemistry
7.
Ecology ; 103(2): e03594, 2022 02.
Article in English | MEDLINE | ID: mdl-34807459

ABSTRACT

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.


Subject(s)
Microbiota , Soil , Bacteria , Ecosystem , Salinity , Soil/chemistry , Soil Microbiology
8.
Sci Rep ; 11(1): 17242, 2021 08 26.
Article in English | MEDLINE | ID: mdl-34446799

ABSTRACT

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.

9.
Sci Rep ; 11(1): 10290, 2021 05 13.
Article in English | MEDLINE | ID: mdl-33986405

ABSTRACT

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.


Subject(s)
Amides/pharmacology , Carbamates/pharmacology , Cyclopropanes/pharmacology , Drug Repositioning , Enzyme Inhibitors/pharmacology , Quinoxalines/pharmacology , RNA Helicases/antagonists & inhibitors , SARS-CoV-2/enzymology , Sulfonamides/pharmacology , Triazoles/pharmacology , Antiviral Agents/pharmacology , Drug Repositioning/methods , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Protein Domains/drug effects , RNA Helicases/chemistry , RNA Helicases/metabolism , SARS-CoV-2/drug effects , Viral Proteins/antagonists & inhibitors , Viral Proteins/chemistry , Viral Proteins/metabolism , COVID-19 Drug Treatment
10.
Target Oncol ; 16(3): 357-367, 2021 05.
Article in English | MEDLINE | ID: mdl-33826036

ABSTRACT

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.


Subject(s)
Abiraterone Acetate/therapeutic use , Prednisone/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Abiraterone Acetate/pharmacology , Aged , Humans , Male , Prednisone/pharmacology , Registries
11.
New Phytol ; 232(3): 1123-1158, 2021 11.
Article in English | MEDLINE | ID: mdl-33159479

ABSTRACT

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.


Subject(s)
Ecosystem , Plants , Atmosphere , Ecology , Phenotype
12.
Target Oncol ; 15(3): 301-315, 2020 06.
Article in English | MEDLINE | ID: mdl-32500294

ABSTRACT

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.


Subject(s)
Prostatic Neoplasms, Castration-Resistant/drug therapy , Adult , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Neoplasm Metastasis , Prospective Studies , Prostatic Neoplasms, Castration-Resistant/mortality , Registries , Survival Rate , Treatment Outcome
13.
Ecol Evol ; 10(4): 2040-2050, 2020 Feb.
Article in English | MEDLINE | ID: mdl-32128136

ABSTRACT

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.

14.
Eur Urol ; 77(3): 380-387, 2020 03.
Article in English | MEDLINE | ID: mdl-31594705

ABSTRACT

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.


Subject(s)
Abiraterone Acetate/administration & dosage , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Benzamides/administration & dosage , Nitriles/administration & dosage , Patient Reported Outcome Measures , Phenylthiohydantoin/administration & dosage , Prednisone/administration & dosage , Prostatic Neoplasms, Castration-Resistant/drug therapy , Aged , Aged, 80 and over , Humans , Male , Neoplasm Metastasis , Prospective Studies , Prostatic Neoplasms, Castration-Resistant/pathology , Time Factors
15.
R Soc Open Sci ; 6(5): 190026, 2019 May.
Article in English | MEDLINE | ID: mdl-31218047

ABSTRACT

Significant changes in the composition and extent of the UK forest cover are likely to take place in the coming decades. Current policy targets an increase in forest area, for example, the Welsh Government aims for forest expansion by 2030, and a purposeful shift from non-native conifers to broadleaved tree species, as identified by the UK Forestry Standard Guidelines on Biodiversity. Using the example of Wales, we aim to generate an evidence-based projection of the impact of contrasting policy scenarios on the state of forests in the near future, with the view of stimulating debate and aiding decisions concerning plausible outcomes of different policies. We quantified changes in different land use and land cover (LULC) classes in Wales between 2007 and 2015 and used a multi-layer perceptron-Markov chain ensemble modelling approach to project the state of Welsh forests in 2030 under the current and an alternative policy scenario. The current level of expansion and restoration of broadleaf forest in Wales is sufficient to deliver on existing policy goals. We also show effects of a more ambitious afforestation policy on the Welsh landscape. In a key finding, the highest intensity of broadleaf expansion is likely to shift from southeastern to more central areas of Wales. The study identifies the key predictors of LULC change in Wales. High-resolution future land cover simulation maps using these predictors offer an evidence-based tool for forest managers and government officials to test the effects of existing and alternative policy scenarios.

16.
BMC Cancer ; 19(1): 60, 2019 Jan 14.
Article in English | MEDLINE | ID: mdl-30642291

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy , Abiraterone Acetate/administration & dosage , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Comorbidity , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Neoplasm Grading , Neoplasm Staging , Prednisone/administration & dosage , Proportional Hazards Models , Prostatic Neoplasms, Castration-Resistant/mortality , Prostatic Neoplasms, Castration-Resistant/pathology , Retrospective Studies , Treatment Outcome
17.
Wellcome Open Res ; 4: 101, 2019.
Article in English | MEDLINE | ID: mdl-32509965

ABSTRACT

Agricultural intensification is a well-known driver of biodiversity loss. Crop diversity and its changes over space and time drive land use intensity and impact biodiversity of agricultural landscapes, while meeting the growing demand for human food and nutrition resources. Loss of biodiversity in agricultural landscapes reduces primary productivity and soil health and erodes a range of other ecosystem services. At present, while having partial understanding of many processes, we lack a general synthesis of our knowledge of the links between crop diversity and biodiversity. We will therefore conduct a systematic review by searching multiple agriculture, ecology and environmental science databases (e.g. Web of Science, Geobase, Agris, AGRICOLA, GreenFILE) to identify studies reporting the impacts of crop diversity and crop type on the biological diversity of fauna and flora in agricultural landscapes. Response variables will include metrics of species richness, abundance, assemblage, community composition and species rarity. Screening, data coding and data extraction will be carried out by one researcher and a subset will be independently carried out by a second researcher for quality control. Study quality and risk of bias will be assessed. Evidence will first be mapped to species/taxa then assessed for further narrative or statistical synthesis based on comparability of results and likely robustness. Gaps in the evidence base will also be identified with a view toward future research and policy directions for nutrition, food systems and ecology.

18.
ESMO Open ; 3(5): e000397, 2018.
Article in English | MEDLINE | ID: mdl-30116592

ABSTRACT

Introduction: Abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) are commonly prescribed for metastatic castration-resistant prostate cancer (mCRPC). Data comparing their effects on patient-reported outcomes (PROs) from routine clinical practice are limited. Methods: AQUARiUS (NCT02813408) is an ongoing, two-cohort, prospective, observational, non-randomised, multicentre, phase IV European study assessing the effects of AAP and ENZ on PROs in 211 patients with mCRPC over 12 months. Patients receive AAP or ENZ per routine clinical practice. Data on cognition, fatigue, pain and health-related quality of life are measured using the Functional Assessment of Cancer Therapy-Cognitive Function, Brief Fatigue Inventory-Short Form, Brief Pain Inventory-Short Form and European Organization for Research and Treatment of Cancer Quality of Life-C30 questionnaires, respectively. Results: This 3-month analysis was conducted in 105 patients; 46 received AAP and 59 received ENZ. There were statistically significant differences in mean change from baseline favouring AAP over ENZ at months 1, 2 and 3 for perceived cognitive impairments and cognitive functioning. At each time-point, ENZ-treated patients had a significantly higher risk of experiencing clinically meaningful worsening in perceived cognitive impairments versus those receiving AAP.Statistically significant differences in mean change from baseline favouring AAP over ENZ were seen for usual level of fatigue and fatigue interference at months 2 and 3 and for current fatigue and worse level of fatigue at month 3. Differences favouring AAP versus ENZ were seen for the fatigue scale of the QLQ-C30 questionnaire (months 1 and 3). There was a significantly higher risk of clinically meaningful worsening in usual level of fatigue with ENZ versus AAP at month 3.No significant differences between cohorts were observed for pain (BPI-SF) at any time-point. Conclusion: This analysis suggests more favourable outcomes with AAP versus ENZ for cognition and fatigue in the first 3 months of treatment initiation for mCRPC. These findings require confirmation from future analyses of data from AQUARiUS from a larger number of patients with a longer follow-up period.

19.
Front Plant Sci ; 9: 664, 2018.
Article in English | MEDLINE | ID: mdl-29868106

ABSTRACT

Invasive plant species represent a serious threat to biodiversity precipitating a sustained global effort to eradicate or at least control the spread of this phenomenon. Current distribution ranges of many invasive species are likely to be modified in the future by land cover and climate change. Thus, invasion management can be made more effective by forecasting the potential spread of invasive species. Rhododendron ponticum (L.) is an aggressive invasive species which appears well suited to western areas of the UK. We made use of MAXENT modeling environment to develop a current distribution model and to assess the likely effects of land cover and climatic conditions (LCCs) on the future distribution of this species in the Snowdonia National park in Wales. Six global circulation models (GCMs) and two representative concentration pathways (RCPs), together with a land cover simulation for 2050 were used to investigate species' response to future environmental conditions. Having considered a range of environmental variables as predictors and carried out the AICc-based model selection, we find that under all LCCs considered in this study, the range of R. ponticum in Wales is likely to contract in the future. Land cover and topographic variables were found to be the most important predictors of the distribution of R. ponticum. This information, together with maps indicating future distribution trends will aid the development of mitigation practices to control R. ponticum.

20.
Sci Rep ; 8(1): 7168, 2018 05 08.
Article in English | MEDLINE | ID: mdl-29740002

ABSTRACT

Species distribution models have been used to predict the distribution of invasive species for conservation planning. Understanding spatial transferability of niche predictions is critical to promote species-habitat conservation and forecasting areas vulnerable to invasion. Grain size of predictor variables is an important factor affecting the accuracy and transferability of species distribution models. Choice of grain size is often dependent on the type of predictor variables used and the selection of predictors sometimes rely on data availability. This study employed the MAXENT species distribution model to investigate the effect of the grain size on model transferability for an invasive plant species. We modelled the distribution of Rhododendron ponticum in Wales, U.K. and tested model performance and transferability by varying grain size (50 m, 300 m, and 1 km). MAXENT-based models are sensitive to grain size and selection of variables. We found that over-reliance on the commonly used bioclimatic variables may lead to less accurate models as it often compromises the finer grain size of biophysical variables which may be more important determinants of species distribution at small spatial scales. Model accuracy is likely to increase with decreasing grain size. However, successful model transferability may require optimization of model grain size.

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