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Summary: Early phase clinical trials provide an initial evaluation of therapies’ risks and benefits to patients, including safety and tolerability, which typically relies on reporting outcomes by investigator and laboratory assessments. Use of patient-reported outcomes (PROs) to inform risks (tolerability) and benefits (improvement in disease symptoms) is more common in later than early phase trials. We convened a two-day expert roundtable covering: (1) the necessity and feasibility of a universal PRO core conceptual model for early phase trials; (2) the practical integration of PROs in early phase trials to inform tolerability assessment, guide dose decisions, or as real-time safety alerts to enhance investigator-reported adverse events. Participants (n = 22) included: patient advocates, regulators, clinicians, statisticians, pharmaceutical representatives, and PRO methodologists working across diverse clinical areas. In this manuscript, we report major recommendations resulting from the roundtable discussions corresponding to each theme. Additionally, we highlight priority areas necessitating further investigation.

Climate and land use changes drive shifts in species distributions, causing variations in species richness. Yet the influence of shifts in species distributions on functional diversity at broad spatial scales remains uncertain. Here, we explored the potential effect of climate and land use changes on the functional diversity of European amphibian assemblages from the present to 2050, along with their effect on species richness. We performed species distribution modelling using a scenario of climate and land use change to estimate current and future potential distributions of 73 species. We estimated functional diversity using morphological and ecological functional traits. Our results highlight the intricate effects of climate and land use changes on taxonomic and functional diversity of amphibians. A climate-induced northward expansion of amphibians is anticipated, with temperature, precipitation, and forest cover prominently shaping future assemblages. Species expected to have shrinking ranges (n = 35) tend to mature sexually at a later age, produce fewer offspring per reproductive event, and live at higher maximum altitudes compared to species expected to expand (n = 38). Furthermore, trait composition changes are expected to exceed predictions based solely on species richness. These changes will vary geographically, with northern regions likely experiencing substantial increases in functional richness and functional redundancy, i.e., the coexistence of species with similar functional roles. Our findings underscore that functional diversity changes might serve as an early warning signal to assess human impacts on biodiversity.

Patient-reported outcomes (PROs) are used in clinical trials to provide valuable evidence on the impact of disease and treatment on patients' symptoms, function and quality of life. High-quality PRO data from trials can inform shared decision-making, regulatory and economic analyses and health policy. Recent evidence suggests the PRO content of past trial protocols was often incomplete or unclear, leading to research waste. To address this issue, international, consensus-based, PRO-specific guidelines were developed: the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)-PRO Extension. The SPIRIT-PRO Extension is a 16-item checklist which aims to improve the content and quality of aspects of clinical trial protocols relating to PRO data collection to minimise research waste, and ultimately better inform patient-centred care. This SPIRIT-PRO explanation and elaboration (E&E) paper provides information to promote understanding and facilitate uptake of the recommended checklist items, including a comprehensive protocol template. For each SPIRIT-PRO item, we provide a detailed description, one or more examples from existing trial protocols and supporting empirical evidence of the item's importance. We recommend this paper and protocol template be used alongside the SPIRIT 2013 and SPIRIT-PRO Extension paper to optimise the transparent development and review of trial protocols with PROs.

Introduction: The purpose of the informed consent form (ICF) is to outline the risks and benefits of an interventional clinical trial to potential participants. The aim of this study was to explore the feasibility of a short addendum to the ICF, summarizing key points most relevant to potential participants. Methods: A sample of 20 ICFs was reviewed against the requirements of the U.S. federal regulation documents and assessed for readability. Alongside the ICF review, we conducted focus groups and one-on-one interviews with people with lung cancer (n = 9) to learn what information was most important when considering participation in a clinical trial using a hypothetical phase 3 ICF. Results: The 20 ICFs reviewed were from phases 1 to 3, expanded-access, and single-patient trials covering predominantly NSCLC; 60% were global. The mean length of the ICFs was 21 (range: 15–34) pages. The average reading level was tenth grade whereas the average U.S. reading level was eighth grade. Readability varied by section, the “purpose of the study” section had the highest reading level. In the qualitative research component, participants were “overwhelmed” by the hypothetical ICF. Participants were also asked to list information for the addendum; their suggestions broadly map to federal regulations. An addendum with reference to sections in the ICF for additional details was well received. Conclusions: The variations in ICF architecture and readability make it difficult for patients to make an informed decision to participate in a clinical trial. Implications extend beyond lung cancer, highlighting key areas for ICF improvements and providing a roadmap for developing a patient-centric addendum.

Introduction: Several studies have highlighted coronavirus disease 2019 (COVID-19)–related disruptions in treatment and care in people living with lung cancer. However, few studies have assessed patient-reported perspectives on treatment disruption. This study aims to report the patient perspectives on the impact of COVID-19, vaccination access, and coverage on people living with lung cancer. Methods: Data are from a larger online longitudinal study being run by a lung cancer nonprofit organization, LUNGevity Foundation. The survey is open to all patients living with lung cancer and their caregivers. These analyses focus on data captured in the COVID-19 module and the vaccine questionnaire. Descriptive statistics were computed for categorical and ordinal variables. Results: Overall, 164 people living with lung cancer completed the COVID-19 module. Of these, 54% reported disruption in access to treatment, appointments, participating in research and clinical trials. Participants living with stage IV disease were likely to be more concerned about COVID-19 (35%) compared with those with stage I, II, and III. More than half (66%) had tested for COVID-19 of this group 88% tested negative. There was a correlation among participants testing positive for COVID-19 and the number of household members who also tested positive for COVID-19. In the sample who completed the vaccine survey, almost all (98%) were vaccinated against COVID-19. When a recommendation came from a health care professional, an oncologist was the most likely referral source (33%). Conclusions: An integrative patient-reported view on the impact of COVID-19 is important for adequate preparation to ensure undisrupted treatment and allocation of resources.

The Biodiversity – Ecosystem Functioning (B–EF) relationship remains a topic of ongoing debate with most studies focusing on primary productivity, and documenting that this relationship takes many forms. It remains unclear if biodiversity drives productivity or productivity shapes biodiversity or the relationship is bidirectional. B-EF studies explore almost exclusively the relationship between species richness and ecosystem functioning, while the role of biotic interactions, a key component of ecosystem functioning, has been neglected. Here, using data of 80 local plant–pollinator networks on 20 Aegean islands, and of gross primary productivity (GPP) from the MODIS satellite, we explored the bidirectional relationship between interaction network structure (nestedness and specialization), species richness (plants and pollinators) and mean and inter-annual variability of GPP. We found that nestedness and specialisation of plant–pollinator networks is driven by mean GPP. However, specialisation alone was a significant predictor of mean GPP, implying that networks tend to be more specialised in low-productivity areas. Pollinator species richness exerted a strong effect on mean GPP with the remaining factors playing a minor role, while the effect of mean GPP on pollinator species richness was weaker. Furthermore, the nestedness of plant–pollinator networks drives inter-annual variability of GPP with more nested networks displaying less variability, which is in accordance with the predictions of the insurance hypothesis. Plant and pollinator species richness were also associated with inter-annual variability of GPP.

The objective of this study was the optimization of the extraction process and the qualitative and quantitative determination of the bioactive metabolites: 12-O-methylcarnosic acid (12MCA), carnosic acid (CA), carnosol (CS), 7-O-methyl-epi-rosmanol (7MER) and rosmanol (RO) in infusions, decoctions, turbulent flow extracts, tinctures and oleolites from three Salvia species: Salvia officinalis L. (common sage, SO), Salvia fruticosa Mill. (Greek sage, SF) and Salvia rosmarinus Spenn (syn Rosmarinus officinalis L.) (rosemary, SR), using Quantitative Proton Nuclear Magnetic Resonance Spectroscopy (1H-qNMR). Regarding the aqueous extracts, decoctions appeared to be richer sources of the studied metabolites than infusions among the three plants. For SR, the turbulent flow extraction under heating was the most efficient one. The optimum time for the preparation of decoctions was found to be 5 min for SF and SO and 15 min for SR. It is noteworthy that SR tinctures were not stable in time due to decomposition of the abietane-type diterpenes CA and CS because of the polar solvent used for their preparation. Contrary to this finding, the oleolites of SR appeared to be very stable. Olive oil as a solvent for extraction was very protective for the contained abietane-type diterpenes. A preliminary stability study on the effect of the storage time of the SF on the abietane-type diterpenes content showed that the total quantity of abietanes decreased by 16.51% and 40.79% after 12 and 36 months, respectively. The results of this investigation also demonstrated that 1H-qNMR is very useful for the analysis of sensitive metabolites, like abietane-type diterpenes, that can be influenced by solvents used in chromatographic analysis.

Climate and land use changes drive shifts in species distributions, causing variations in species richness. Yet the influence of shifts in species distributions on functional diversity at broad spatial scales remains uncertain. Here, we explored the potential effect of climate and land use changes on the functional diversity of European amphibian assemblages from the present to 2050, along with their effect on species richness. We performed species distribution modelling using a scenario of climate and land use change to estimate current and future potential distributions of 73 species. We estimated functional diversity using morphological and ecological functional traits. Our results highlight the intricate effects of climate and land use changes on taxonomic and functional diversity of amphibians. A climate-induced northward expansion of amphibians is anticipated, with temperature, precipitation, and forest cover prominently shaping future assemblages. Species expected to have shrinking ranges (n = 35) tend to mature sexually at a later age, produce fewer offspring per reproductive event, and live at higher maximum altitudes compared to species expected to expand (n = 38). Furthermore, trait composition changes are expected to exceed predictions based solely on species richness. These changes will vary geographically, with northern regions likely experiencing substantial increases in functional richness and functional redundancy, i.e., the coexistence of species with similar functional roles. Our findings underscore that functional diversity changes might serve as an early warning signal to assess human impacts on biodiversity. [ABSTRACT FROM AUTHOR]

Biological invasions are one of the main threats to biodiversity, but they also offer insights on different ecological processes, as highlighted by the hypotheses posited to explain the phenomenon. We explore the relative importance of different hypotheses using biotic (native diversity) and abiotic factors (climate and landscape configuration) as proxies driving the spatial pattern of alien plant biodiversity in Greece. The strongest predictor of alien species richness is native species richness. Landscape heterogeneity boosts this relationship, but native and alien species prefer different conditions. Landscape composition and configuration explain more of the variance of alien diversity than of native diversity, with native diversity increasing at more naturally vegetated areas and alien diversity at agricultural lands. Climate is associated more strongly with native diversity than with alien diversity, with native diversity increasing in colder regions and alien diversity in warmer regions. The transportation network was associated with higher alien species richness but not with native species richness, highlighting the importance of propagule/colonization pressure. These differences might indicate that aliens occupy part of the niche space that is not preferred by the natives and thus allow us to speculate on the role of limiting similarity as a driving force.

Biodiversity promotes the functioning of ecosystems, and functional redundancy safeguards this functioning against environmental changes. However, what drives functional redundancy remains unclear. We analyzed taxonomic diversity, functional diversity (richness and β-diversity) and functional redundancy patterns of British butterflies. We explored the effect of temperature and landscape-related variables on richness and redundancy using generalized additive models, and on β-diversity using generalized dissimilarity models. The species richness-functional richness relationship was saturating, indicating functional redundancy in species-rich communities. Assemblages did not deviate from random expectations regarding functional richness. Temperature exerted a significant effect on all diversity aspects and on redundancy, with the latter relationship being unimodal. Landscape-related variables played a role in driving observed patterns. Although taxonomic and functional β-diversity were highly congruent, the model of taxonomic β-diversity explained more deviance than the model of functional β-diversity did. Species-rich butterfly assemblages exhibited functional redundancy. Climate- and landscape-related variables emerged as significant drivers of diversity and redundancy. Τaxonomic β-diversity was more strongly associated with the environmental gradient, while functional β-diversity was driven more strongly by stochasticity. Temperature promoted species richness and β-diversity, but warmer areas exhibited lower levels of functional redundancy. This might be related to the land uses prevailing in warmer areas (e.g., agricultural intensification).

The challenge of predicting the distribution of alien species has long been a focus of invasion ecology. Herein, we assessed biotic and abiotic factors from the 1980s as potential predictors of alien bird species patterns 20 years later in the state of New York. To assess the ability of each factor to predict future alien species patterns, we analysed the influence of biotic (native taxonomic, functional and phylogenetic diversity, and human population density) and abiotic (climate and land use) factors from the 1980s on the observed alien species richness patterns in the 2000s and the temporal change in the composition of the alien communities between the 1980s and the 2000s using both single-predictor and multivariate models. Alien species richness from the 1980s was a reliable predictor of the alien species richness and temporal beta-diversity patterns in the 2000s. Among abiotic factors, maximum temperature and agricultural land-uses constituted sufficient predictors of future alien species richness and better predictors than the native biotic factors. The performance of single-predictor models was generally weaker in predicting temporal alien beta-diversity; however, past alien species richness and maximum temperature again outperformed the other factors. Predictions and management decisions should focus on warm and agricultural areas, as well as areas with an already high number of established alien species.