68 research outputs found

    Hybrid healthcare governance for improvement? Combining top-down and bottom-up approaches to public sector regulation

    Get PDF
    Improving healthcare governance is an enduring challenge for policy-makers. We consider two national healthcare regulators adopting novel ‘hybrid’ regulatory control strategies in pursuit of improvement. Hybrids combine elements usually found separately. Scotland and Ireland’s regulators combine: (1) top-down formal regulatory mechanisms deterring breaches of protocol and enacting penalties where they occur (e.g. standard-setting, monitoring, accountability); and (2) bottom-up capacity building and persuasive encouragement of adherence to guidance by professional self-determination, implementation and improvement support (e.g. training, stimulating interventions). We identify socio-historical contextual factors constraining and enabling regulatory hybridity, whether and how it can be recreated, and circumstances when the approaches might be delivered separately. Using our findings, we develop a goal-oriented governance framework illustrating distinct, yet complementary, national and local organizational roles: (1) ensuring the adoption and implementation of best-practice, (2) enabling and (3) empowering staff to adapt and add to national mandates and (4) embedding cultures of improvement

    Fire, water, and biodiversity in the sierra nevada: A possible triple win

    Get PDF
    Reducing the risk of large, severe wildfires while also increasing the security of mountain water supplies and enhancing biodiversity are urgent priorities in western US forests. After a century of fire suppression, Yosemite and Sequoia-Kings Canyon National Parks located in California’s Sierra Nevada initiated programs to manage wildfires and these areas present a rare opportunity to study the effects of restored fire regimes. Forest cover decreased during the managed wildfire period and meadow and shrubland cover increased, especially in Yosemite’s Illilouette Creek basin that experienced a 20% reduction in forest area. These areas now support greater pyrodiversity and consequently greater landscape and species diversity. Soil moisture increased and drought-induced tree mortality decreased, especially in Illilouette where wildfires have been allowed to burn more freely resulting in a 30% increase in summer soil moisture. Modeling suggests that the ecohydrological co-benefits of restoring fire regimes are robust to the projected climatic warming. Support will be needed from the highest levels of government and the public to maintain existing programs and expand them to other forested areas

    Whole brain radiotherapy (WBRT) after local treatment of brain metastases in melanoma patients: Statistical Analysis Plan

    Get PDF
    Background: The WBRTMel trial is a multinational, open-label, phase III randomised controlled trial comparing whole brain radiotherapy (WBRT) to observation following local treatment of one to three melanoma brain metastases with surgery and/or stereotactic irradiation. The primary trial endpoint was to determine the effect of adding WBRT to local treatment on distant intracranial control, and the secondary endpoints were neurocognitive function, quality of life (QoL), performance status, overall survival, death from intracranial causes, death from melanoma and cost-effectiveness. Objective: The objective of this update is to outline and publish the pre-determined statistical analysis plan (SAP) before the database lock and the start of analysis. Methods: The SAP describes basic analysis principles, methods for dealing with a range of commonly encountered data analysis issues and the specific statistical procedures for analysing efficacy and safety outcomes. The SAP was approved after closure of recruitment and before completion of patient follow-up. It outlines the planned primary analyses and a range of subgroup and sensitivity analyses regarding the clinical and QoL outcomes. Health economic outcomes are not included in this plan but will be analysed separately. The SAP will be adhered to for the final data analysis of this trial to avoid analysis bias arising from knowledge of the data. Results: The resulting SAP is consistent with best practice and will allow open and transparent reporting. Conclusion: We have developed a SAP for the WBRTMel trial which will be followed to ensure high-quality standards of internal validity to minimise analysis bias

    Phenotypic plasticity in cell walls of maize brown midrib mutants is limited by lignin composition

    Get PDF
    The hydrophobic cell wall polymer lignin is deposited in specialized cells to make them impermeable to water and prevent cell collapse as negative pressure or gravitational force is exerted. The variation in lignin subunit composition that exists among different species, and among different tissues within the same species suggests that lignin subunit composition varies depending on its precise function. In order to gain a better understanding of the relationship between lignin subunit composition and the physico-chemical properties of lignified tissues, detailed analyses were performed of near-isogenic brown midrib2 (bm2), bm4, bm2-bm4, and bm1-bm2-bm4 mutants of maize. This investigation was motivated by the fact that the bm2-bm4 double mutant is substantially shorter, displays drought symptoms even when well watered, and will often not develop reproductive organs, whereas the phenotypes of the individual bm single mutants and double mutant combinations other than bm2-bm4 are only subtly different from the wild-type control. Detailed cell wall compositional analyses revealed midrib-specific reductions in Klason lignin content in the bm2, bm4, and bm2-bm4 mutants relative to the wild-type control, with reductions in both guaiacyl (G)- and syringyl (S)-residues. The cellulose content was not different, but the reduction in lignin content was compensated by an increase in hemicellulosic polysaccharides. Linear discriminant analysis performed on the compositional data indicated that the bm2 and bm4 mutations act independently of each other on common cell wall biosynthetic steps. After quantitative analysis of scanning electron micrographs of midrib sections, the variation in chemical composition of the cell walls was shown to be correlated with the thickness of the sclerenchyma cell walls, but not with xylem vessel surface area. The bm2-bm4 double mutant represents the limit of phenotypic plasticity in cell wall composition, as the bm1-bm2-bm4 and bm2-bm3-bm4 mutants did not develop into mature plants, unlike the triple mutants bm1-bm2-bm3 and bm1-bm3-bm4

    The swan genome and transcriptome, its not all black and white

    Get PDF
    BACKGROUND: The Australian black swan (Cygnus atratus) is an iconic species with contrasting plumage to that of the closely related northern hemisphere white swans. The relative geographic isolation of the black swan may have resulted in a limited immune repertoire and increased susceptibility to infectious diseases, notably infectious diseases from which Australia has been largely shielded. Unlike mallard ducks and the mute swan (Cygnus olor), the black swan is extremely sensitive to highly pathogenic avian influenza. Understanding this susceptibility has been impaired by the absence of any available swan genome and transcriptome information. RESULTS: Here, we generate the first chromosome-length black and mute swan genomes annotated with transcriptome data, all using long-read based pipelines generated for vertebrate species. We use these genomes and transcriptomes to show that unlike other wild waterfowl, black swans lack an expanded immune gene repertoire, lack a key viral pattern-recognition receptor in endothelial cells and mount a poorly controlled inflammatory response to highly pathogenic avian influenza. We also implicate genetic differences in SLC45A2 gene in the iconic plumage of the black swan. CONCLUSION: Together, these data suggest that the immune system of the black swan is such that should any avian viral infection become established in its native habitat, the black swan would be in a significant peril. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13059-022-02838-0

    Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans

    Get PDF
    Antibody responses to SARS-CoV-2 can be detected in most infected individuals 10–15 d after the onset of COVID-19 symptoms. However, due to the recent emergence of SARS-CoV-2 in the human population, it is not known how long antibody responses will be maintained or whether they will provide protection from reinfection. Using sequential serum samples collected up to 94 d post onset of symptoms (POS) from 65 individuals with real-time quantitative PCR-confirmed SARS-CoV-2 infection, we show seroconversion (immunoglobulin (Ig)M, IgA, IgG) in >95% of cases and neutralizing antibody responses when sampled beyond 8 d POS. We show that the kinetics of the neutralizing antibody response is typical of an acute viral infection, with declining neutralizing antibody titres observed after an initial peak, and that the magnitude of this peak is dependent on disease severity. Although some individuals with high peak infective dose (ID50 > 10,000) maintained neutralizing antibody titres >1,000 at >60 d POS, some with lower peak ID50 had neutralizing antibody titres approaching baseline within the follow-up period. A similar decline in neutralizing antibody titres was observed in a cohort of 31 seropositive healthcare workers. The present study has important implications when considering widespread serological testing and antibody protection against reinfection with SARS-CoV-2, and may suggest that vaccine boosters are required to provide long-lasting protection

    Characterizing Emerging Canine H3 Influenza Viruses.

    Get PDF
    The continual emergence of novel influenza A strains from non-human hosts requires constant vigilance and the need for ongoing research to identify strains that may pose a human public health risk. Since 1999, canine H3 influenza A viruses (CIVs) have caused many thousands or millions of respiratory infections in dogs in the United States. While no human infections with CIVs have been reported to date, these viruses could pose a zoonotic risk. In these studies, the National Institutes of Allergy and Infectious Diseases (NIAID) Centers of Excellence for Influenza Research and Surveillance (CEIRS) network collaboratively demonstrated that CIVs replicated in some primary human cells and transmitted effectively in mammalian models. While people born after 1970 had little or no pre-existing humoral immunity against CIVs, the viruses were sensitive to existing antivirals and we identified a panel of H3 cross-reactive human monoclonal antibodies (hmAbs) that could have prophylactic and/or therapeutic value. Our data predict these CIVs posed a low risk to humans. Importantly, we showed that the CEIRS network could work together to provide basic research information important for characterizing emerging influenza viruses, although there were valuable lessons learned

    Upscaling marine forest restoration: challenges, solutions and recommendations from the Green Gravel Action Group

    Get PDF
    IntroductionTo counteract the rapid loss of marine forests globally and meet international commitments of the UN Decade on Ecosystem Restoration and the Convention on Biological Diversity ‘30 by 30’ targets, there is an urgent need to enhance our capacity for macroalgal restoration. The Green Gravel Action Group (GGAG) is a global network of 67 members that are working on the restoration of a diverse range of macroalgal forests and it aims to facilitate knowledge exchange to fast-track innovation and implementation of outplanting approaches worldwide. MethodsHere, we overview 25 projects conducted by members of the group that are focused on testing and developing techniques for macroalgal restoration. Based on these projects, we summarise the major challenges associated with scaling up the area of marine forests restored. ResultsWe identify several critical challenges that currently impede more widespread rollout of effective large-scale macroalgal restoration worldwide: 1) funding and capacity limitations, 2) difficulties arising from conditions at restoration sites, 3) technical barriers, and 4) challenges at the restoration-policy interface. DiscussionDespite these challenges, there has been substantial progress, with an increasing number of efforts, community engagement and momentum towards scaling up activities in recent years. Drawing on the collective expertise of the GGAG, we outline key recommendations for the scaling up of restoration efforts to match the goals of international commitments. These include the establishment of novel pathways to fund macroalgal restoration activities, building skills and capacity, harnessing emerging innovations in mobile hatchery and seeding technologies, and the development of the scientific and governance frameworks necessary to implement and monitor macroalgal restoration projects at scale

    Children must be protected from the tobacco industry's marketing tactics.

    Get PDF
    corecore