Nurse rock microclimates significantly buffer exposure to freezing T temperature and moderate summer temperature

Nurse tree canopies mitigate exposure to freezing temperatures that could result in injury or mortality to the saguaro cactus (Carnegiea gigantea). Abiotic objects have been hypothesized to provide similar beneficial microclimates. We used data loggers at 11 nurse rock sites to record daily daytime summer maximum and winter nighttime minimum temperatures at Saguaro National Park, Arizona, to examine the effectiveness of rocks to moderate seasonal temperature extremes in the microclimate. Temperatures at rock sites averaged 2 °C warmer than exposed open control sites in winter. We found that the efficiency of rocks to act as insulators significantly increased as temperature at control sites decreased, consistent with studies of tree canopies, and that the insulation effect lasted throughout the night. In summer, rocks reduced exposure to maximum temperatures but did not offer significantly more cooling at higher temperatures. Our results suggest that the protection from freezing temperature offered by rocks in winter is more ecologically beneficial to the saguaro than extreme temperature amelioration during summer in the cold-limited frontiers of the species’ range

Implementation of a novel antimicrobial stewardship strategy for rural facilities utilising telehealth

A significant portion of healthcare takes place in small hospitals, and many are located in rural and regional areas. Facilities in these regions frequently do not have adequate resources to implement an onsite antimicrobial stewardship programme and there are limited data relating to their implementation and effectiveness. We present an innovative model of providing a specialist telehealth antimicrobial stewardship service utilising a centralised service (Queensland Statewide Antimicrobial Stewardship Program) to a rural Hospital and Health Service. Results of a 2-year post-implementation follow-up showed an improvement in adherence to guidelines [33.7% (95% CI 27.0–40.4%) vs. 54.1% (95% CI 48.7–59.5%)] and appropriateness of antimicrobial prescribing [49.0% (95% CI 42.2–55.9%) vs. 67.5% (95% CI 62.7–72.4%) (P < 0.001). This finding was sustained after adjustment for hospitals, with improvement occurring sequentially across the years for adherence to guidelines [adjusted odds ratio (aOR) = 2.44, 95% CI 1.70–3.51] and appropriateness of prescribing (aOR = 2.48, 95% CI 1.70–3.61). There was a decrease in mean total antibiotic use (DDDs/1000 patient-days) between the years 2016 (52.82, 95% CI 44.09–61.54) and 2018 (39.74, 95% CI 32.76–46.73), however this did not reach statistical significance. Additionally, there was a decrease in mean hospital length of stay (days) from 2016 (3.74, 95% CI 3.08–4.41) to 2018 (2.55, 95% CI 1.98–3.12), although this was not statistically significant. New telehealth-based models of antimicrobial stewardship can be effective in improving prescribing in rural areas. Programmes similar to ours should be considered for rural facilities

Competency, confidence and conflicting evidence: key issues affecting health visitors' use of research evidence in practice

BACKGROUND: Health visitors play a pivotal position in providing parents with up-to-date evidence-based care on child health. The recent controversy over the safety of the MMR vaccine has drawn attention to the difficulties they face when new research which raises doubts about current guidelines and practices is published. In the aftermath of the MMR controversy, this paper investigates the sources health visitors use to find out about new research evidence on immunisation and examines barriers and facilitators to using evidence in practice. It also assesses health visitors' confidence in using research evidence. METHODS: Health visitors were recruited from the 2007 UK Community Practitioners' and Health Visitors' Association conference. All delegates were eligible to complete the questionnaire if in their current professional role they advise parents about childhood immunisation or administer vaccines to children. Of 228 who were eligible, 185 completed the survey (81.1%). RESULTS: These health visitors used a wide range of resources to find out about new research evidence on childhood immunisation. Popular sources included information leaflets and publications, training days, nursing journals and networking with colleagues. A lack of time was cited as the main barrier to searching for new evidence. The most common reason given for not using research in practice was a perception of conflicting research evidence. Understanding the evidence was a key facilitator. Health visitors expressed less confidence about searching and explaining research on childhood immunisation than evidence on weaning and a baby's sleep position. CONCLUSION: Even motivated health visitors feel they lack the time and, in some cases, the skills to locate and appraise research evidence. This research suggests that of the provision of already-appraised research would help to keep busy health professionals informed, up-to-date and confident in responding to public concerns, particularly when there is apparently conflicting evidence. Health visitors' relative lack of confidence about research on immunisation suggests there is still a job to be done in rebuilding confidence in evidence on childhood immunisation. Further research on what makes evidence more comprehensible, convincing and useable would contribute to understanding how to bridge the gulf between evidence and practice

Issues of context, capacity and scale: Essential conditions and missing links for a sustainable blue economy

Funding: This work was supported by the United Kingdom Research and Innovation (UKRI), Global Challenges Research Fund (GCRF), One Ocean Hub (Grant Ref: NE/S008950/1).The blue economy has roots in the international arena of sustainable development and sets out to unlock opportunities for economy and society whilst protecting and enhancing marine environments. To date there has been no analysis of how this overarching intention for sustainability has influenced the rapid development of blue economy policies at national and regional scales. In this article, we analyse the synergies and conflicts between blue economy policies from a diversity of national and regional policies and the UN Sustainable Development Goals. We show that to maintain critical alignment with targets for sustainability, place-based contextual development of blue economies that meet the needs of all actors is necessary. These needs relate to ensuring resilience against future environmental and political shocks, the maintenance of the ecological basis for thriving blue economies, and capacity development at all levels to support effective and equitable governance. Results indicate that co-production will be important to achieve sustainable blue economies.Publisher PDFPeer reviewe

Patient-reported wellbeing and clinical disease measures over time captured by multivariate trajectories of disease activity in individuals with juvenile idiopathic arthritis in the UK: a multicentre prospective longitudinal study

Background: Juvenile idiopathic arthritis (JIA) is a heterogeneous disease, the signs and symptoms of which can be summarised with use of composite disease activity measures, including the clinical Juvenile Arthritis Disease Activity Score (cJADAS). However, clusters of children and young people might experience different global patterns in their signs and symptoms of disease, which might run in parallel or diverge over time. We aimed to identify such clusters in the 3 years after a diagnosis of JIA. The identification of these clusters would allow for a greater understanding of disease progression in JIA, including how physician-reported and patient-reported outcomes relate to each other over the JIA disease course. / Methods: In this multicentre prospective longitudinal study, we included children and young people recruited before Jan 1, 2015, to the Childhood Arthritis Prospective Study (CAPS), a UK multicentre inception cohort. Participants without a cJADAS score were excluded. To assess groups of children and young people with similar disease patterns in active joint count, physician’s global assessment, and patient or parental global evaluation, we used latent profile analysis at initial presentation to paediatric rheumatology and multivariate group-based trajectory models for the following 3 years. Optimal models were selected on the basis of a combination of model fit, clinical plausibility, and model parsimony. / Finding: Between Jan 1, 2001, and Dec 31, 2014, 1423 children and young people with JIA were recruited to CAPS, 239 of whom were excluded, resulting in a final study population of 1184 children and young people. We identified five clusters at baseline and six trajectory groups using longitudinal follow-up data. Disease course was not well predicted from clusters at baseline; however, in both cross-sectional and longitudinal analyses, substantial proportions of children and young people had high patient or parent global scores despite low or improving joint counts and physician global scores. Participants in these groups were older, and a higher proportion of them had enthesitisrelated JIA and lower socioeconomic status, compared with those in other groups. / Interpretation: Almost one in four children and young people with JIA in our study reported persistent, high patient or parent global scores despite having low or improving active joint counts and physician’s global scores. Distinct patient subgroups defined by disease manifestation or trajectories of progression could help to better personalise health-care services and treatment plans for individuals with JIA. / Funding: Medical Research Council, Versus Arthritis, Great Ormond Street Hospital Children’s Charity, Olivia’s Vision, and National Institute for Health Researc

saeRS and sarA Act Synergistically to Repress Protease Production and Promote Biofilm Formation in Staphylococcus aureus

Mutation of the staphylococcal accessory regulator (sarA) limits biofilm formation in diverse strains of Staphylococcus aureus, but there are exceptions. One of these is the commonly studied strain Newman. This strain has two defects of potential relevance, the first being mutations that preclude anchoring of the fibronectin-binding proteins FnbA and FnbB to the cell wall, and the second being a point mutation in saeS that results in constitutive activation of the saePQRS regulatory system. We repaired these defects to determine whether either plays a role in biofilm formation and, if so, whether this could account for the reduced impact of sarA in Newman. Restoration of surface-anchored FnbA enhanced biofilm formation, but mutation of sarA in this fnbA-positive strain increased rather than decreased biofilm formation. Mutation of sarA in an saeS-repaired derivative of Newman (P18L) or a Newman saeRS mutant (ΔsaeRS) resulted in a biofilm-deficient phenotype like that observed in clinical isolates, even in the absence of surface-anchored FnbA. These phenotypes were correlated with increased production of extracellular proteases and decreased accumulation of FnbA and/or Spa in the P18L and ΔsaeRS sarA mutants by comparison to the Newman sarA mutant. The reduced accumulation of Spa was reversed by mutation of the gene encoding aureolysin, while the reduced accumulation of FnbA was reversed by mutation of the sspABC operon. These results demonstrate that saeRS and sarA act synergistically to repress the production of extracellular proteases that would otherwise limit accumulation of critical proteins that contribute to biofilm formation, with constitutive activation of saeRS limiting protease production, even in a sarA mutant, to a degree that can be correlated with increased enhanced capacity to form a biofilm. Although it remains unclear whether these effects are mediated directly or indirectly, studies done with an sspA::lux reporter suggest they are mediated at a transcriptional level

Identification of a Novel, Small Molecule Partial Agonist for the Cyclic AMP Sensor, EPAC1

Screening of a carefully selected library of 5,195 small molecules identified 34 hit compounds that interact with the regulatory cyclic nucleotide-binding domain (CNB) of the cAMP sensor, EPAC1. Two of these hits (I942 and I178) were selected for their robust and reproducible inhibitory effects within the primary screening assay. Follow-up characterisation by ligand observed nuclear magnetic resonance (NMR) revealed direct interaction of I942 and I178 with EPAC1 and EPAC2-CNBs in vitro. Moreover, in vitro guanine nucleotide exchange factor (GEF) assays revealed that I942 and, to a lesser extent, I178 had partial agonist properties towards EPAC1, leading to activation of EPAC1, in the absence of cAMP, and inhibition of GEF activity in the presence of cAMP. In contrast, there was very little agonist action of I942 towards EPAC2 or protein kinase A (PKA). To our knowledge, this is the first observation of non-cyclic-nucleotide small molecules with agonist properties towards EPAC1. Furthermore, the isoform selective agonist nature of these compounds highlights the potential for the development of small molecule tools that selectively up-regulate EPAC1 activity

Persistence survey of Toxic Shock Syndrome toxin-1 producing Staphylococcus aureus and serum antibodies to this superantigen in five groups of menstruating women

Background: Menstrual Toxic Shock Syndrome (mTSS) is thought to be associated with the vaginal colonization with specific strains of Staphylococcus aureus TSST-1 in women who lack sufficient antibody titers to this toxin. There are no published studies that examine the seroconversion in women with various colonization patterns of this organism. Thus, the aim of this study was to evaluate the persistence of Staphylococcus aureus colonization at three body sites (vagina, nares, and anus) and serum antibody to toxic shock syndrome toxin-producing Staphylococcus aureus among a small group of healthy, menstruating women evaluated previously in a larger study. Methods: One year after the completion of that study, 311 subjects were recalled into 5 groups. Four samples were obtained from each participant at several visits over an additional 6-11 month period: 1) an anterior nares swab; 2) an anal swab; 3) a vagina swab; and 4) a blood sample. Gram stain, a catalase test, and a rapid S. aureus-specific latex agglutination test were performed to phenotypically identify S. aureus from sample swabs. A competitive ELISA was used to quantify TSST-1 production. Human TSST-1 IgG antibodies were determined from the blood samples using a sandwich ELISA method. Results: We found only 41% of toxigenic S. aureus and 35.5% of non-toxigenic nasal carriage could be classified as persistent. None of the toxigenic S. aureus vaginal or anal carriage could be classified as persistent. Despite the low persistence of S. aureus colonization, subjects colonized with a toxigenic strain were found to display distributions of antibody titers skewed toward higher titers than other subjects. Seven percent (5/75) of subjects became seropositive during recall, but none experienced toxic shock syndrome-like symptoms. Conclusions: Nasal carriage of S. aureus appears to be persistent and the best predicator of subsequent colonization, whereas vaginal and anal carriage appear to be more transient. From these findings, it appears that antibody titers in women found to be colonized with toxigenic S. aureus remained skewed toward higher titers whether or not the colonies were found to be persistent or transient in nature. This suggests that colonization at some point in time is sufficient to elevate antibody titer levels and those levels appear to be persistent. Results also indicate that women can become seropositive without experiencing signs or symptoms of toxic shock syndrome

Asc1 Supports Cell-Wall Integrity Near Bud Sites by a Pkc1 Independent Mechanism

Background: The yeast ribosomal protein Asc1 is a WD-protein family member. Its mammalian ortholog, RACK1 was initially discovered as a receptor for activated protein C kinase (PKC) that functions to maintain the active conformation of PKC and to support its movement to target sites. In the budding yeast though, a connection between Asc1p and the PKC signaling pathway has never been reported. Methodology/Principal Findings: In the present study we found that asc1-deletion mutant (asc1D) presents some of the hallmarks of PKC signaling mutants. These include an increased sensitivity to staurosporine, a specific Pkc1p inhibitor, and susceptibility to cell-wall perturbing treatments such as hypotonic- and heat shock conditions and zymolase treatment. Microscopic analysis of asc1D cells revealed cell-wall invaginations near bud sites after exposure to hypotonic conditions, and the dynamic of cells ’ survival after this stress further supports the involvement of Asc1p in maintaining the cell-wall integrity during the mid-to late stages of bud formation. Genetic interactions between asc1 and pkc1 reveal synergistic sensitivities of a double-knock out mutant (asc1D/pkc1D) to cell-wall stress conditions, and high basal level of PKC signaling in asc1D. Furthermore, Asc1p has no effect on the cellular distribution or redistribution of Pkc1p at optimal or at cell-wall stress conditions. Conclusions/Significance: Taken together, our data support the idea that unlike its mammalian orthologs, Asc1p act

Heterogeneous Response to a Quorum-Sensing Signal in the Luminescence of Individual Vibrio fischeri

The marine bacterium Vibrio fischeri regulates its bioluminescence through a quorum sensing mechanism: the bacterium releases diffusible small molecules (autoinducers) that accumulate in the environment as the population density increases. This accumulation of autoinducer (AI) eventually activates transcriptional regulators for bioluminescence as well as host colonization behaviors. Although V.fischeri quorum sensing has been extensively characterized in bulk populations, far less is known about how it performs at the level of the individual cell, where biochemical noise is likely to limit the precision of luminescence regulation. We have measured the time-dependence and AI-dependence of light production by individual V.fischeri cells that are immobilized in a perfusion chamber and supplied with a defined concentration of exogenous AI. We use low-light level microscopy to record and quantify the photon emission from the cells over periods of several hours as they respond to the introduction of AI. We observe an extremely heterogeneous response to the AI signal. Individual cells differ widely in the onset time for their luminescence and in their resulting brightness, even in the presence of high AI concentrations that saturate the light output from a bulk population. The observed heterogeneity shows that although a given concentration of quorum signal may determine the average light output from a population of cells, it provides far weaker control over the luminescence output of each individual cell