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We studied the floral reproductive biology and nectar chemistry of Jaltomata grandiflora (Solanaceae), an apparently rare perennial of Michoacán, Mexico. During day 1, flowers are pistillate (stigma receptive, anthers not yet presenting pollen); flowers close for the night. Early in the morning of day 2, the corolla re-opens, stamens elongate to five times their earlier length, and anthers dehisce; the dehisced anthers remain about 2 mm from the stigma for much of day 2. In the afternoon of day 2, the corolla again closes, the corolla–androecium abscises, and only then can pollen be seen on the stigma. Protogyny and herkogamy likely promote outcrossing during days 1 and 2, respectively. Autonomous self-pollination takes place at the end of the corolla's life and allows fruit and seed production in the absence of pollinators but results in fruits that are lighter and contain fewer seeds than fruits resulting from manual self-pollinations. Carbohydrates from floral nectar samples were separated and quantified using hydrophilic interaction liquid chromatography coupled with corona charged aerosol detection. In nectar, mean sucrose concentration (0.482 mg/mg nectar), is about 10 and five times higher than glucose (0.043 mg/mg nectar) and fructose (0.095 mg/mg nectar) concentrations.

Background: Translational gaps exist in implementing health innovations rapidly in clinical practice. Pragmatic effectiveness and implementation studies, therefore, play a pivotal role in understanding how high-value health innovations could be deployed and delivered in healthcare systems to reduce barriers to adoption and provide more rapid patient benefit. Victorion-spirit is an ongoing pragmatic, 9-month, phase IIIb, open-label, multicentre, randomised controlled study evaluating the implementation, patient experience, and delivery of the subcutaneous lipid-lowering therapy, inclisiran sodium 300 mg, in participants with elevated low-density lipoprotein cholesterol (LDL-C) who are on established lipid-lowering medication, or have been recommended lipid-lowering therapy, but are unable to tolerate treatment. Methods: Victorion-spirit utilises a type 1 hybrid effectiveness-implementation design, where the primary objective is to demonstrate superiority of inclisiran with or without (±) behavioural support versus standard of care (SOC; e.g., statin and/or other lipid-lowering therapies) + behavioural support in terms of percentage reduction in LDL-C from baseline to Day 270 in a primary care setting. Secondary objectives will evaluate implementation of inclisiran ± behavioural support versus SOC + behavioural support through assessment of patient satisfaction and patient activation/empowerment after treatment at Day 90; adherence to cardiovascular disease self-management; and serious adverse event profile. Additionally, a process evaluation ascertaining the views of patients, providers and national health service (NHS) commissioners will explore barriers and enablers to integrating inclisiran within primary care. Conclusions: The results of Victorion-spirit have potential to change our approach to lipid management and inform further implementation efforts in healthcare systems, such as the NHS. Trial registration: ClinicalTrials.gov NCT04087400.

Combining existing knowledge of museum exhibition visitor experience with concepts of User Experience (UX), a model for Museum Exhibition User Experience (MEUX) is presented. The model was developed from research interviews and surveys with UK museum professionals and presents the museum exhibition experience from both museum and visitor perspectives. Its use as an evaluation tool for visitor experience is explored at Oxford University Museum of Natural History (OUMNH). In comparing results with those from staff, a disconnect emerged between museum and visitor preferences on motivations for visiting and what outcomes emerge from visits. The incorporation of the theoretical MEUX model into museum practice enables holistic conceptualization of the visitor experience through the pragmatic and hedonic qualities of an exhibition. With the development of further evaluation tools, this framework and methodology accurately captures institutional and visitor preferences and can evaluate how the development decisions of museums influence and impact the visitor experience.

International audience; Earth's climate cooled markedly during the late Miocene from 12 to 5 million years ago, with far-reaching consequences for global ecosystems. However, the driving forces of these changes remain controversial. A major obstacle to progress is the uncertainty over the role played by greenhouse gas radiative forcing. Here we present boron isotope compositions for planktic foraminifera, which record carbon dioxide change for the interval of most rapid cooling, the late Miocene cooling event between 7 and 5 Ma. Our record suggests that CO2 declined by some 100 ppm over this two-million-year-long interval to a minimum at approximately 5.9 Ma. Having accounted for non-CO2 greenhouse gasses and slow climate feedbacks, we estimate global mean surface temperature change for a doubling of CO2—equilibrium climate sensitivity—to be 3.9 °C (1.8-6.7 °C at 95% confidence) on the basis of comparison of our record of radiative forcing from CO2 with a record of global mean surface temperature change. We conclude that changes in CO2 and climate were closely coupled during the latest Miocene and that equilibrium climate sensitivity was within range of estimates for the late Pleistocene, other intervals of the Cenozoic and the twenty-first century as presented by the Intergovernmental Panel on Climate Change.

Introduction: Missions beyond low Earth orbit (LEO) will expose astronauts to ionizing radiation (IR) in the form of solar energetic particles (SEP) and galactic cosmic rays (GCR) including high atomic number and energy (HZE) nuclei. The gastrointestinal (GI) system is documented to be highly radiosensitive with even relatively low dose IR exposures capable of inducing mucosal lesions and disrupting epithelial barrier function. IR is also an established risk factor for colorectal cancer (CRC) with several studies examining long-term GI effects of SEP/GCR exposure using tumor-prone APC mouse models. Studies of acute short-term effects of modeled space radiation exposures in wildtype mouse models are more limited and necessary to better define charged particle- induced GI pathologies and test novel medical countermeasures (MCMs) to promote astronaut safety.Methods: In this study, we performed ground-based studies where male and female C57BL/6J mice were exposed to γ-rays, 50 MeV protons, or 1 GeV/n Fe-56 ions at the NASA Space Radiation Laboratory (NSRL) with histology and immunohistochemistry endpoints measured in the first 24 h post-irradiation to define immediate SEP/GCR-induced GI alterations.Results: Our data show that unlike matched γ-ray controls, acute exposures to protons and iron ions disrupts intestinal function and induces mucosal lesions, vascular congestion, epithelial barrier breakdown, and marked enlargement of mucosa-associated lymphoid tissue. We also measured kinetics of DNA double-strand break (DSB) repair using gamma-H2AX- specific antibodies and apoptosis via TUNEL labeling, noting the induction and disappearance of extranuclear cytoplasmic DNA marked by gamma-H2AX only in the charged particle-irradiated samples. We show that 18 h pre-treatment with curcumin-loaded nanolipoprotein particles (cNLPs) delivered via IV injection reduces DSB-associated foci levels and apoptosis and restore crypt villi lengths.Discussion: These data improve our understanding of physiological alterations in the GI tract immediately following exposures to modeled space radiations and demonstrates effectiveness of a promising space radiation MCM.

The mid-Pliocene (3.3–3.0 Ma) is the most recent period in Earth’s history of sustained, global warmth analogous to predicted near-future climates. Despite considerable efforts to characterize and understand the climate dynamics of the mid-Pliocene, the deep ocean and its response to this warming remains poorly understood. Here we present new mid-Pliocene Mg/Ca and Δ47 (“clumped isotope”) temperatures from the deep Pacific and North Atlantic oceans. These records cover the transition from Marine Isotope Stage (MIS) M2 — considered the most pronounced “glacial” stage of the mid-Pliocene — to the warm KM5 interglacial. We find that a large (>4 °C) temperature gradient existed between these two basins throughout that interval, with the deep North Atlantic considerably warmer and likely saltier than at present. We interpret our results to indicate that the deep Pacific and North Atlantic oceans were bathed by water masses with very different physical properties during the mid-Pliocene, and that only limited deep oceanic exchange occurred between the two basins. Our results point to a fundamentally different mode of ocean circulation or mixing compared to the present, where heat and salt is distributed from the North Atlantic into the Pacific. The amplitude of cooling observed at both sites during MIS M2 suggests that changes in benthic δ18O associated with this cold stage were mostly driven by temperature change in the deep ocean rather than ice volume.

Purpose: VEGF receptor (VEGFR) kinases are important drug targets in oncology that affect function of systemic endothelial cells. To discover genetic markers that affect VEGFR inhibitor pharmacodynamics, we performed a genome-wide association study of serum soluble vascular VEGFR2 concentrations [sVEGFR2], a pharmacodynamic biomarker for VEGFR2 inhibitors.Experimental Design: We conducted a genome-wide association study (GWAS) of [sVEGFR2] in 736 healthy Old Order Amish volunteers. Gene variants identified from the GWAS were genotyped serially in a cohort of 128 patients with advanced solid tumor with baseline [sVEGFR2] measurements, and in 121 patients with renal carcinoma with [sVEGFR2] measured before and during pazopanib therapy.Results: rs34231037 (C482R) in KDR, the gene encoding sVEGFR2 was found to be highly associated with [sVEGFR2], explaining 23% of the variance (P = 2.7 × 10−37). Association of rs34231037 with [sVEGFR2] was replicated in 128 patients with cancer with comparable effect size (P = 0.025). Furthermore, rs34231037 was a significant predictor of changes in [sVEGFR2] in response to pazopanib (P = 0.01).Conclusion: Our findings suggest that genome-wide analysis of phenotypes in healthy populations can expedite identification of candidate pharmacogenetic markers. Genotyping for germline variants in KDR may have clinical utility in identifying patients with cancer with unusual sensitivity to effects of VEGFR2 kinase inhibitors. Clin Cancer Res; 21(2); 365–72. ©2014 AACR.

AimsTo explore barriers to, and facilitators of, adherence to compression therapy, from the perspective of people with venous leg ulcers.DesignAn interpretive, qualitative, descriptive study involving interviews with patients.MethodsParticipants were purposively sampled from respondents to a survey exploring attitudes to compression therapy in people with venous leg ulcers. Sampling continued until data saturation: 25 interviews between December 2019 and July 2020. Inductive thematic analysis of interview transcripts was undertaken to create a framework for the data, followed by deductive analysis informed by the Common-Sense Model of Self-Regulation.ResultsA range of knowledge and understanding about the cause of venous leg ulcers and the mechanisms of compression therapy was demonstrated, which was not particularly related to adherence. Participants talked about their experience with different compression methods and their concerns about the length of time healing could take. They also spoke about aspects of the organization of services which affected their care.ConclusionIdentifying specific, individual barriers/facilitators to compression therapy is not simple, rather factors combine to make adherence more or less likely or possible. There was no clear relationship between an understanding of the cause of VLUs or the mechanism of compression therapy and adherence; different compression therapies presented different challenges for patients; unintentional non-adherence was frequently mentioned; and the organization of services could impact on adherence. Ways in which people could be supported to adhere to compression therapy are indicated. Implications for practice include issues relating to communication with patients; taking into account patients' lifestyles and ensuring that they know about useful ‘aids’; providing services that are accessible and provide continuity of appropriately trained staff; minimizing unintentional non-adherence; and acknowledging that healthcare professionals will always need to support/advise those who cannot tolerate compression.ImpactCompression therapy is a cost-effective, evidence-based treatment for venous leg ulcers. However, there is evidence that patients do not always adhere to this therapy and there is limited research investigating reasons why patients do not wear compression. The study found no clear relationship between an understanding of the cause of VLUs or the mechanism of compression therapy and adherence; that different compression therapies presented different challenges for patients; that unintentional non-adherence was frequently mentioned and that the organization of services could impact on adherence. Attending to these findings offers the opportunity to increase the proportion of people undergoing appropriate compression therapy and achieving complete wound healing, the main outcome desired by this group.Patient/Public ContributionA patient representative sits on the Study Steering Group, contributing to the work from developing the study protocol and interview schedule to interpretation and discussion of findings. Members of a Wounds Research Patient and Public Involvement Forum were consulted about interview questions.

Boron isotopes in planktonic foraminifera are a widely used proxy to determine ancient surface seawater pH, and by extension atmospheric CO2 concentration and climate forcing on geological time scales. Yet, to reconstruct absolute values for pH and CO2, we require a δ11Bforam-borate to pH calibration and independent determinations of ocean temperature, salinity, a second carbonate parameter, and the boron isotope composition of seawater. Although δ11B-derived records of atmospheric CO2 have been shown to perform well against ice core-based CO2 reconstructions, these tests have been performed at only a few locations and with limited temporal resolution. Here we present two highly resolved CO2 records for the late Pleistocene from ODP Sites 999 and 871. Our δ11B-derived CO2 record shows a very good agreement with the ice core CO2 record with an average offset of 4.6 ± 49 (2σ) ppm, and a RMSE of 25 ppm, with minor short-lived overestimations of CO2 (of up to ~50 ppm) occurring during some glacial onsets. We explore potential drivers of this disagreement and conclude that partial dissolution of foraminifera has a minimal effect on the CO2 offset. We also observe that the general agreement between δ11B -derived and ice core CO2 is improved by optimising the δ11Bforam-borate calibration. Despite these minor issues a strong linear relationship between relative change in climate forcing from CO2 (from ice core data) and pH change (from δ11B) exists over the late Pleistocene, confirming that pH change is a robust proxy of climate forcing over relatively short (2 beyond the reach of the ice cores and can help improve determinations of climate sensitivity for ancient time intervals.