Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy.

The poor clinical outcome in pancreatic ductal adenocarcinoma (PDA) is attributed to intrinsic chemoresistance and a growth-permissive tumor microenvironment. Conversion of quiescent to activated pancreatic stellate cells (PSCs) drives the severe stromal reaction that characterizes PDA. Here, we reveal that the vitamin D receptor (VDR) is expressed in stroma from human pancreatic tumors and that treatment with the VDR ligand calcipotriol markedly reduced markers of inflammation and fibrosis in pancreatitis and human tumor stroma. We show that VDR acts as a master transcriptional regulator of PSCs to reprise the quiescent state, resulting in induced stromal remodeling, increased intratumoral gemcitabine, reduced tumor volume, and a 57% increase in survival compared to chemotherapy alone. This work describes a molecular strategy through which transcriptional reprogramming of tumor stroma enables chemotherapeutic response and suggests vitamin D priming as an adjunct in PDA therapy. PAPERFLICK:

Meta-analysis reveals that the effects of precipitation change on soil and litter fauna in forests depend on body size.

Anthropogenic climate change is altering precipitation regimes at a global scale. While precipitation changes have been linked to changes in the abundance and diversity of soil and litter invertebrate fauna in forests, general trends have remained elusive due to mixed results from primary studies. We used a meta-analysis based on 430 comparisons from 38 primary studies to address associated knowledge gaps, (i) quantifying impacts of precipitation change on forest soil and litter fauna abundance and diversity, (ii) exploring reasons for variation in impacts and (iii) examining biases affecting the realism and accuracy of experimental studies. Precipitation reductions led to a decrease of 39% in soil and litter fauna abundance, with a 35% increase in abundance under precipitation increases, while diversity impacts were smaller. A statistical model containing an interaction between body size and the magnitude of precipitation change showed that mesofauna (e.g. mites, collembola) responded most to changes in precipitation. Changes in taxonomic richness were related solely to the magnitude of precipitation change. Our results suggest that body size is related to the ability of a taxon to survive under drought conditions, or to benefit from high precipitation. We also found that most experiments manipulated precipitation in a way that aligns better with predicted extreme climatic events than with predicted average annual changes in precipitation and that the experimental plots used in experiments were likely too small to accurately capture changes for mobile taxa. The relationship between body size and response to precipitation found here has far-reaching implications for our ability to predict future responses of soil biodiversity to climate change and will help to produce more realistic mechanistic soil models which aim to simulate the responses of soils to global change.

Tapping into non-English-language science for the conservation of global biodiversity.

The widely held assumption that any important scientific information would be available in English underlies the underuse of non-English-language science across disciplines. However, non-English-language science is expected to bring unique and valuable scientific information, especially in disciplines where the evidence is patchy, and for emergent issues where synthesising available evidence is an urgent challenge. Yet such contribution of non-English-language science to scientific communities and the application of science is rarely quantified. Here, we show that non-English-language studies provide crucial evidence for informing global biodiversity conservation. By screening 419,679 peer-reviewed papers in 16 languages, we identified 1,234 non-English-language studies providing evidence on the effectiveness of biodiversity conservation interventions, compared to 4,412 English-language studies identified with the same criteria. Relevant non-English-language studies are being published at an increasing rate in 6 out of the 12 languages where there were a sufficient number of relevant studies. Incorporating non-English-language studies can expand the geographical coverage (i.e., the number of 2° × 2° grid cells with relevant studies) of English-language evidence by 12% to 25%, especially in biodiverse regions, and taxonomic coverage (i.e., the number of species covered by the relevant studies) by 5% to 32%, although they do tend to be based on less robust study designs. Our results show that synthesising non-English-language studies is key to overcoming the widespread lack of local, context-dependent evidence and facilitating evidence-based conservation globally. We urge wider disciplines to rigorously reassess the untapped potential of non-English-language science in informing decisions to address other global challenges. Please see the Supporting information files for Alternative Language Abstracts.

First-in-human study of oleclumab, a potent, selective anti-CD73 monoclonal antibody, alone or in combination with durvalumab in patients with advanced solid tumors.

BACKGROUND: CD73 upregulation in tumors leads to local immunosuppression. This phase I, first-in-human study evaluated oleclumab (MEDI9447), an anti-CD73 human IgG1λ monoclonal antibody, alone or with durvalumab in patients with advanced colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), or epidermal growth factor receptor-mutant non-small-cell lung cancer (NSCLC). METHODS: Patients received oleclumab 5-40 mg/kg (dose-escalation) or 40 mg/kg (dose-expansion) intravenously every 2 weeks (Q2W), alone (escalation only) or with durvalumab 10 mg/kg intravenously Q2W. RESULTS: 192 patients were enrolled, 66 during escalation and 126 (42 CRC, 42 PDAC, 42 NSCLC) during expansion. No dose-limiting toxicities occurred during escalation. In the monotherapy and combination therapy escalation cohorts, treatment-related adverse events (TRAEs) occurred in 55 and 54%, respectively, the most common being fatigue (17 and 25%). In the CRC, PDAC, and NSCLC expansion cohorts, 60, 57, and 45% of patients had TRAEs, respectively; the most common were fatigue (15%), diarrhea (9%), and rash (7%). Free soluble CD73 and CD73 expression on peripheral T cells and tumor cells showed sustained decreases, accompanied by reduced CD73 enzymatic activity in tumor cells. Objective response rate during escalation was 0%. Response rates in the CRC, PDAC, and NSCLC expansion cohorts were 2.4% (1 complete response [CR]), 4.8% (1 CR, 1 partial response [PR]), and 9.5% (4 PRs), respectively; 6-month progression-free survival rates were 5.4, 13.2, and 16.0%. CONCLUSIONS: Oleclumab ± durvalumab had a manageable safety profile, with pharmacodynamic activity reflecting oleclumab's mechanism of action. Evidence of antitumor activity was observed in tumor types that are generally immunotherapy resistant. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT02503774; date of registration, July 17, 2015.

Mass spectrometry quantifies target engagement for a KRASG12C inhibitor in FFPE tumor tissue.

BACKGROUND: Quantification of drug-target binding is critical for confirming that drugs reach their intended protein targets, understanding the mechanism of action, and interpreting dose-response relationships. For covalent inhibitors, target engagement can be inferred by free target levels before and after treatment. Targeted mass spectrometry assays offer precise protein quantification in complex biological samples and have been routinely applied in pre-clinical studies to quantify target engagement in frozen tumor tissues for oncology drug development. However, frozen tissues are often not available from clinical trials so it is critical that assays are applicable to formalin-fixed, paraffin-embedded (FFPE) tissues in order to extend mass spectrometry-based target engagement studies into clinical settings. METHODS: Wild-type RAS and RASG12C was quantified in FFPE tissues by a highly optimized targeted mass spectrometry assay that couples high-field asymmetric waveform ion mobility spectrometry (FAIMS) and parallel reaction monitoring (PRM) with internal standards. In a subset of samples, technical reproducibility was evaluated by analyzing consecutive tissue sections from the same tumor block and biological variation was accessed among adjacent tumor regions in the same tissue section. RESULTS: Wild-type RAS protein was measured in 32 clinical non-small cell lung cancer tumors (622-2525 amol/µg) as measured by FAIMS-PRM mass spectrometry. Tumors with a known KRASG12C mutation (n = 17) expressed a wide range of RASG12C mutant protein (127-2012 amol/µg). The variation in wild-type RAS and RASG12C measurements ranged 0-18% CV across consecutive tissue sections and 5-20% CV among adjacent tissue regions. Quantitative target engagement was then demonstrated in FFPE tissues from 2 xenograft models (MIA PaCa-2 and NCI-H2122) treated with a RASG12C inhibitor (AZD4625). CONCLUSIONS: This work illustrates the potential to expand mass spectrometry-based proteomics in preclinical and clinical oncology drug development through analysis of FFPE tumor biopsies.

Specific targeting of the KRAS mutational landscape in myeloma as a tool to unveil the elicited antitumor activity.

Alterations in KRAS have been identified as the most recurring somatic variants in the multiple myeloma (MM) mutational landscape. Combining DNA and RNA sequencing, we studied 756 patients and observed KRAS as the most frequently mutated gene in patients at diagnosis; in addition, we demonstrated the persistence or de novo occurrence of the KRAS aberration at disease relapse. Small-molecule inhibitors targeting KRAS have been developed; however, they are selective for tumors carrying the KRASG12C mutation. Therefore, there is still a need to develop novel therapeutic approaches to target the KRAS mutational events found in other tumor types, including MM. We used AZD4785, a potent and selective antisense oligonucleotide that selectively targets and downregulates all KRAS isoforms, as a tool to dissect the functional sequelae secondary to KRAS silencing in MM within the context of the bone marrow niche and demonstrated its ability to significantly silence KRAS, leading to inhibition of MM tumor growth, both in vitro and in vivo, and confirming KRAS as a driver and therapeutic target in MM.

Exploring the expression of Adenosine Pathway-Related Markers CD73 and CD39 in Colorectal and Pancreatic Carcinomas Characterized by Multiplex Immunofluorescence: A Pilot Study.

INTRODUCTION: Generating high levels of immunosuppressive adenosine in the tumor microenvironment contributes to cancer immune evasion. CD39 and CD73 hydrolyze adenosine triphosphate into adenosine; thus, efforts have been made to target this pathway for cancer immunotherapy. Our objective was optimizing a multiplex immunofluorescence (mIF) panel to explore the role of CD39 and CD73 within the tumor microenvironment. MATERIALS AND METHODS: In three-time points, a small cohort (n=8 ) of colorectal and pancreatic adenocarcinomas were automated staining using an mIF panel against CK, CD3, CD8, CD20, CD39, CD73 and CD68 to compare them with individual markers immunohistochemistry (IHC) for internal panel validation. Densities of immune cells and distances from different tumor-associated immune cells to tumor cells were exploratory assessment and compared with clinicopathologic variables and outcomes. RESULTS: Comparing the three-time points and individual IHC staining results, we demonstrated high reproducibility of the mIF panel. CD39 and CD73 expression was low in malignant cells; the exploratory analysis showed higher densities of CD39 expression by various cells, predominantly stromal cells, followed by T cells, macrophages, and B cells. No expression of CD73 by B cells or macrophages was detected. Distance analysis revealed proximity of cytotoxic T cells, macrophages, and T cells expressing CD39 to malignant cells, suggesting a close regulatory signal driven by this adenosine marker. CONCLUSIONS: We optimized an mIF panel for detection of markers in the adenosine pathway, an emerging clinically relevant pathway. The densities and spatial distribution demonstrated that this pathway may modulate aspects of the tumor immune microenvironment.

What is the Price of Conservation? A Review of the Status Quo and Recommendations for Improving Cost Reporting.

Wildlife conservation is severely limited by funding. Therefore, to maximize biodiversity outcomes, assessing financial costs of interventions is as important as assessing effectiveness. We reviewed the reporting of costs in studies testing the effectiveness of conservation interventions: 13.3% of the studies provided numeric costs, and 8.8% reported total costs. Even fewer studies broke down these totals into constituent costs, making it difficult to assess the relevance of costs to different contexts. Cost reporting differed between continents and the taxa or habitats targeted by interventions, with higher cost reporting in parts of the Global South. A further analysis of data focused on mammals identified that interventions related to agriculture, invasive species, transport, and residential development reported costs more frequently. We identify opportunities for conservationists to improve future practice through encouraging systematic reporting and collation of intervention costs, using economic evaluation tools, and increasing understanding and skills in finance and economics.

Dynamic meta-analysis: a method of using global evidence for local decision making.

BACKGROUND: Meta-analysis is often used to make generalisations across all available evidence at the global scale. But how can these global generalisations be used for evidence-based decision making at the local scale, if the global evidence is not perceived to be relevant to local decisions? We show how an interactive method of meta-analysis-dynamic meta-analysis-can be used to assess the local relevance of global evidence. RESULTS: We developed Metadataset ( www.metadataset.com ) as a proof-of-concept for dynamic meta-analysis. Using Metadataset, we show how evidence can be filtered and weighted, and results can be recalculated, using dynamic methods of subgroup analysis, meta-regression, and recalibration. With an example from agroecology, we show how dynamic meta-analysis could lead to different conclusions for different subsets of the global evidence. Dynamic meta-analysis could also lead to a rebalancing of power and responsibility in evidence synthesis, since evidence users would be able to make decisions that are typically made by systematic reviewers-decisions about which studies to include (e.g. critical appraisal) and how to handle missing or poorly reported data (e.g. sensitivity analysis). CONCLUSIONS: In this study, we show how dynamic meta-analysis can meet an important challenge in evidence-based decision making-the challenge of using global evidence for local decisions. We suggest that dynamic meta-analysis can be used for subject-wide evidence synthesis in several scientific disciplines, including agroecology and conservation biology. Future studies should develop standardised classification systems for the metadata that are used to filter and weight the evidence. Future studies should also develop standardised software packages, so that researchers can efficiently publish dynamic versions of their meta-analyses and keep them up-to-date as living systematic reviews. Metadataset is a proof-of-concept for this type of software, and it is open source. Future studies should improve the user experience, scale the software architecture, agree on standards for data and metadata storage and processing, and develop protocols for responsible evidence use.

Implications of scale dependence for cross-study syntheses of biodiversity differences.

Biodiversity studies are sensitive to well-recognised temporal and spatial scale dependencies. Cross-study syntheses may inflate these influences by collating studies that vary widely in the numbers and sizes of sampling plots. Here we evaluate sources of inaccuracy and imprecision in study-level and cross-study estimates of biodiversity differences, caused by within-study grain and sample sizes, biodiversity measure, and choice of effect-size metric. Samples from simulated communities of old-growth and secondary forests demonstrated influences of all these parameters on the accuracy and precision of cross-study effect sizes. In cross-study synthesis by formal meta-analysis, the metric of log response ratio applied to measures of species richness yielded better accuracy than the commonly used Hedges' g metric on species density, which dangerously combined higher precision with persistent bias. Full-data analyses of the raw plot-scale data using multilevel models were also susceptible to scale-dependent bias. We demonstrate the challenge of detecting scale dependence in cross-study synthesis, due to ubiquitous covariation between replication, variance and plot size. We propose solutions for diagnosing and minimising bias. We urge that empirical studies publish raw data to allow evaluation of covariation in cross-study syntheses, and we recommend against using Hedges' g in biodiversity meta-analyses.

The challenge of biased evidence in conservation.

Efforts to tackle the current biodiversity crisis need to be as efficient and effective as possible given chronic underfunding. To inform decision-makers of the most effective conservation actions, it is important to identify biases and gaps in the conservation literature to prioritize future evidence generation. We used the Conservation Evidence database to assess the state of the global literature that tests conservation actions for amphibians and birds. For the studies in the database, we investigated their spatial and taxonomic extent and distribution across biomes, effectiveness metrics, and study designs. Studies were heavily concentrated in Western Europe and North America for birds and particularly for amphibians, and temperate forest and grassland biomes were highly represented relative to their percentage of land coverage. Studies that used the most reliable study designs-before-after control-impact and randomized controlled trials-were the most geographically restricted and scarce in the evidence base. There were negative spatial relationships between the numbers of studies and the numbers of threatened and data-deficient species worldwide. Taxonomic biases and gaps were apparent for amphibians and birds-some entire orders were absent from the evidence base-whereas others were poorly represented relative to the proportion of threatened species they contained. Metrics used to evaluate effectiveness of conservation actions were often inconsistent between studies, potentially making them less directly comparable and evidence synthesis more difficult. Testing conservation actions on threatened species outside Western Europe, North America, and Australasia should be prioritized. Standardizing metrics and improving the rigor of study designs used to test conservation actions would also improve the quality of the evidence base for synthesis and decision-making.

El Desafío de la Evidencia Sesgada en la Conservación Resumen Los esfuerzos para lidiar con la actual crisis de la biodiversidad necesitan ser tan eficientes y efectivos como sea posible dado el crónico subfinanciamiento. Para informar a los órganos de decisión sobre las acciones de conservación más efectivas, es importante identificar los sesgos y las brechas en la literatura de la conservación para priorizar generación de evidencias en el futuro. Usamos la base de datos Conservation Evidence para evaluar el estado de la literatura mundial que analiza las acciones para la conservación de anfibios y aves. Para los estudios dentro de la base de datos, investigamos su extensión espacial y taxonómica y su distribución a lo largo de biomas, medidas de efectividad y diseños de estudio. Los estudios se concentraron principalmente en Europa Occidental y en América del Norte en el caso de las aves y particularmente para los anfibios. Los biomas con mayor representación en relación con su porcentaje de cobertura de suelo fueron el bosque templado y los pastizales. Los estudios que utilizaron el diseño más confiable - impacto del control antes- después y ensayos controlados al azar - fueron los que presentaron mayor restricción geográfica y menor presencia dentro de la base de evidencias. También encontramos relaciones espaciales negativas entre el número de estudios y el número de especies amenazadas o con pocos datos a nivel mundial. Los sesgos y las brechas taxonómicas fueron evidentes para los anfibios y las aves - hubo órdenes enteros ausentes en la base de evidencias - mientras que otros taxones estuvieron representados pobremente en relación con la proporción de especies amenazadas que albergan. Las medidas utilizadas para evaluar la efectividad de las acciones de conservación con frecuencia fueron incompatibles entre los estudios, lo que las hace potencialmente menos comparables directamente y también dificulta la síntesis de las evidencias. Se debe priorizar el análisis de las acciones para la conservación de las especies que se encuentran fuera de Europa Occidental, América del Norte y Australasia. La estandarización de las medidas y el mejoramiento del rigor de los diseños de estudio que se usan para evaluar las acciones de conservación también mejoraría la calidad de la base de evidencias para la síntesis y la toma de decisiones.

Bridging the Gap: Using Interspecialty High-Fidelity Simulation to Improve Skills in Adolescent Emergency Medicine.

INTRODUCTION: Adolescents are attending emergency departments (EDs) in increasing numbers, accounting for 21% attendances in the United Kingdom. A recent report by the Northern Ireland Commissioner for Children and Young People highlighted deficiencies in the support offered by EDs to adolescents. AIM: The aim of this study was to develop a high-fidelity simulation-based course focused on managing common adolescent presentations to the ED. METHODOLOGY: A 1-day mixed-modality course comprising of simulations, lectures, and skill stations, mapped to the pediatric and emergency medicine curriculum, was designed. The faculty developed and delivered 8 high-fidelity simulations. Precourse and immediate postcourse questionnaires were used to assess confidence levels and gain qualitative data. Delayed feedback was collected at 3 months. RESULTS: There were 36 participants; 86% (n = 31) completed the precourse feedback, 96% (n = 34) completed the postcourse feedback, and 47% (n = 17) completed the delayed feedback. There was a statistically significant increase in self-reported confidence across all domains with a median increase of 21.25% immediately, sustained at 20% on delayed 3-month feedback. Qualitative feedback noted a change in practice, "I used (the knowledge) regularly while working in children's A + E." CONCLUSIONS: This was a feasible, high-fidelity simulation-based study day covering the key components of adolescent medicine. The sustained increase in confidence at 3 months and the positive qualitative and quantitative feedback are supportive of the use of simulation to improve adolescent emergency care.

Fifteen-minute consultation: How to be the paediatrician at a trauma call.

The management of paediatric trauma patients can be complex, involving a coordinated multidisciplinary approach. Paediatricians form an integral part of the trauma team and are often tasked with managing circulation. In this article, we will discuss the assessment of catastrophic haemorrhage and 'circulation' through the viewpoint of a paediatrician via a case discussion. This will include initial investigations and management, noting the time critical nature in identifying and stopping catastrophic haemorrhage. The discussion will comment on how to address hypovolaemic shock and touch on the role of imaging.

Ten-year assessment of the 100 priority questions for global biodiversity conservation.

In 2008, a group of conservation scientists compiled a list of 100 priority questions for the conservation of the world's biodiversity. However, now almost a decade later, no one has yet published a study gauging how much progress has been made in addressing these 100 high-priority questions in the peer-reviewed literature. We took a first step toward reexamining the 100 questions to identify key knowledge gaps that remain. Through a combination of a questionnaire and a literature review, we evaluated each question on the basis of 2 criteria: relevance and effort. We defined highly relevant questions as those that - if answered - would have the greatest impact on global biodiversity conservation and quantified effort based on the number of review publications addressing a particular question, which we used as a proxy for research effort. Using this approach, we identified a set of questions that, despite being perceived as highly relevant, have been the focus of relatively few review publications over the past 10 years. These questions covered a broad range of topics but predominantly tackled 3 major themes: conservation and management of freshwater ecosystems, role of societal structures in shaping interactions between people and the environment, and impacts of conservation interventions. We believe these questions represent important knowledge gaps that have received insufficient attention and may need to be prioritized in future research.

The Production of Methane, Acetone, "Cold" CO and Oxygenated Species from IsoPropyl Alcohol in a Non-Thermal Plasma: An In-Situ FTIR Study.

This paper reports in situ Fourier transform infrared (FTIR) spectroscopic studies on the nonthermal plasma reaction of isopropyl alcohol in dinitrogen at Macor (a ceramic containing oxides of Al, Mg, and Si) and the analogous thermally driven process. While isopropyl alcohol did not react at the Macor at temperatures up to 600 °C, the study of the nonthermal plasma-driven process at the ceramic led to unexpected chemistry hitherto not observed, primarily the reaction of IPA in dinitrogen at short time scales to produce methane, HCN, acetone and "cold" CO at ca. 115 K. The CO, methane, and HCN rapidly established steady state concentrations, pointing to the need for faster FTIR studies: at longer times, isophorone and a "polymethylacetylene-like" polymer were formed as a brown oil. The observation of the steady-state gases and brown oil suggested parallel pathways in the plasma, the latter taking place at the plasma/catalyst interface, and the former in the plasma remote from the catalyst. Replacing dinitrogen with argon completely inhibited or negated the production of the oil, had no effect upon the processes taking place in the plasma remote from the Macor, and instead resulted in the production of acetylene.

Effects of Age, Power Output, and Cadence on Energy Expenditure and Lower Limb Antagonist Muscle Coactivation During Cycling.

It is unknown if higher antagonist muscle coactivation is a factor contributing to greater energy expenditure of cycling in older adults. We determined how age, power output, and cadence affect energy expenditure and lower limb antagonist muscle coactivation during submaximal cycling. Thirteen younger and 12 older male participants completed 6-min trials at four power output-cadence conditions (75 W-60 rpm, 75 W-90 rpm, 125 W-60 rpm, and 125 W-90 rpm) while electromyographic and metabolic energy consumption data were collected. Knee and ankle coactivation indices were calculated using vastus lateralis, biceps femoris, gastrocnemius, and tibialis anterior electromyography data. Energy expenditure of cycling was greater in older compared with younger participants at 125 W (p = .002) and at 90 rpm (p = .026). No age-related differences were observed in the magnitude or duration of coactivation about the knee or ankle (p > .05). Our results indicated that the knee and ankle coactivation is not a substantive factor contributing to greater energy expenditure of cycling in older adults.

Unusual Role of Excited State Mixing in the Enhancement of Photoinduced Ligand Exchange in Ru(II) Complexes.

Four Ru(II) complexes were prepared bearing two new tetradentate ligands, cyTPA and 1-isocyTPQA, which feature a piperidine ring that provides a structurally rigid backbone and facilitates the installation of other donors as the fourth chelating arm, while avoiding the formation of stereoisomers. The photophysical properties and photochemistry of [Ru(cyTPA)(CH3CN)2]2+ (1), [Ru(1-isocyTPQA)(CH3CN)2]2+ (2), [Ru(cyTPA)(py)2]2+ (3), and [Ru(1-isocyTPQA)(py)2]2+ (4) were compared. The quantum yield for the CH3CN/H2O ligand exchange of 2 was measured to be Φ400 = 0.033(3), 5-fold greater than that of 1, Φ400 = 0.0066(3). The quantum yields for the py/H2O ligand exchange of 3 and 4 were lower, 0.0012(1) and 0.0013(1), respectively. DFT and related calculations show the presence of a highly mixed 3MLCT/3ππ* excited state as the lowest triplet state in 2, whereas the lowest energy triplet states in 1, 3, and 4 were calculated to be 3LF in nature. The mixed 3MLCT/3ππ* excited state places significant spin density on the quinoline moiety of the 1-isocyTPQA ligand positioned trans to the photolabile CH3CN ligand in 2, suggesting the presence of a trans-type influence in the excited state that enhances ligand exchange. Ultrafast spectroscopy was used to probe the excited states of 1-4, which confirmed that the mixed 3MLCT/3ππ* excited state in 2 promotes ligand dissociation, representing a new manner to effect photoinduced ligand exchange. The findings from this work can be used to design improved complexes for applications that require efficient ligand dissociation, as well as for those that require minimal deactivation of the 3MLCT state through low-lying metal-centered states.

Impacts of invasive plants on carbon pools depend on both species' traits and local climate.

Invasive plants can alter ecosystem properties, leading to changes in the ecosystem services on which humans depend. However, generalizing about these effects is difficult because invasive plants represent a wide range of life forms, and invaded ecosystems differ in their plant communities and abiotic conditions. We hypothesize that differences in traits between the invader and native species can be used to predict impacts and so aid generalization. We further hypothesize that environmental conditions at invaded sites modify the effect of trait differences and so combine with traits to predict invasion impacts. To test these hypotheses, we used systematic review to compile data on changes in aboveground and soil carbon pools following non-native plant invasion from studies across the World. Maximum potential height (Hmax ) of each species was drawn from trait databases and other sources. We used meta-regression to assess which of invasive species' Hmax , differences in this height trait between native and invasive plants, and climatic water deficit, a measure of water stress, were good predictors of changes in carbon pools following invasion. We found that aboveground biomass in invaded ecosystems relative to uninvaded ones increased as the value of Hmax of invasive relative to native species increased, but that this effect was reduced in more water stressed ecosystems. Changes in soil carbon pools were also positively correlated with the relative Hmax of invasive species, but were not altered by water stress. This study is one of the first to show quantitatively that the impact of invasive species on an ecosystem may depend on differences in invasive and native species' traits, rather than solely the traits of invasive species. Our study is also the first to show that the influence of trait differences can be altered by climate. Further developing our understanding of the impacts of invasive species using this framework could help researchers to identify not only potentially dangerous invasive species, but also the ecosystems where impacts are likely to be greatest.

Structural Features of Europium(II)-Containing Cryptates That Influence Relaxivity.

EuII -containing complexes were studied with respect to properties relevant to their use as contrast agents for magnetic resonance imaging. The influences of molecular parameters and field strength on relaxivity were studied for a series of EuII -containing cryptates and their adducts with ß-cyclodextrins, poly-ß-cyclodextrins, and human serum albumin. Solid- and solution-phase characterization of EuII -containing complexes is presented that demonstrates the presence of inner-sphere molecules of water. Additionally, relaxivity, water-exchange rate, rotational correlation time, and electronic relaxation times were determined using variable-temperature 17 O NMR, nuclear magnetic relaxation dispersion, and electron paramagnetic resonance spectroscopic techniques. These results are expected to be instrumental in the design of future EuII -based contrast agents.