Are lower levels of red blood cell transfusion more cost-effective than liberal levels after cardiac surgery? Findings from the TITRe2 randomised controlled trial.

OBJECTIVE: To assess the incremental cost and cost-effectiveness of a restrictive versus a liberal red blood cell transfusion threshold after cardiac surgery. DESIGN: A within-trial cost-effectiveness analysis with a 3-month time horizon, based on a multicentre superiority randomised controlled trial from the perspective of the National Health Service (NHS) and personal social services in the UK. SETTING: 17 specialist cardiac surgery centres in UK NHS hospitals. PARTICIPANTS: 2003 patients aged >16 years undergoing non-emergency cardiac surgery with a postoperative haemoglobin of <9 g/dL. INTERVENTIONS: Restrictive (transfuse if haemoglobin <7.5 g/dL) or liberal (transfuse if haemoglobin <9 g/dL) threshold during hospitalisation after surgery. MAIN OUTCOME MEASURES: Health-related quality of life measured using the EQ-5D-3L to calculate quality-adjusted life years (QALYs). RESULTS: The total costs from surgery up to 3 months were £17 945 and £18 127 in the restrictive and liberal groups (mean difference is -£182, 95% CI -£1108 to £744). The cost difference was largely attributable to the difference in the cost of red blood cells. Mean QALYs to 3 months were 0.18 in both groups (restrictive minus liberal difference is 0.0004, 95% CI -0.0037 to 0.0045). The point estimate for the base-case cost-effectiveness analysis suggested that the restrictive group was slightly more effective and slightly less costly than the liberal group and, therefore, cost-effective. However, there is great uncertainty around these results partly due to the negligible differences in QALYs gained. CONCLUSIONS: We conclude that there is no clear difference in the cost-effectiveness of restrictive and liberal thresholds for red blood cell transfusion after cardiac surgery. TRIAL REGISTRATION NUMBER: ISRCTN70923932; Results

A review of assessment methods for river hydromorphology

The work leading to this paper has received funding for the EU’s FP7 under Grant Agreement No. 282656 (REFORM

River Styles and stream power analysis reveal the diversity of fluvial morphology in a Philippine tropical catchment

Availability of data and materials: Following review, all GIS datasets will be made available through the NERC data repository.Copyright © The Authors 2022. Characterisation of hydromorphological attributes is crucial for effective river management. Such information is often overlooked in tropical regions such as the Philippines where river management strategies mainly focus on issues around water quality and quantity. We address this knowledge gap using the River Styles Framework as a template to identify the diversity of river morphodynamics. We identify eight distinct River Styles (river types) in the Bislak catchment (586 km2) in the Philippines, showing considerable geomorphic diversity within a relatively small catchment area. Three River Styles in a Confined valley setting occupy 57% of the catchment area, another three in a partly confined valley setting occupy 37%, and two in the remaining 6% are found in a laterally unconfined valley setting. Five characteristic downstream patterns of River Styles were identified across the catchment. We observe that variation in channel slope for a given catchment area (i.e., total stream power) is insufficient to differentiate between river types. Hence, topographic analyses should be complemented with broader framed, catchment-specific approaches to river characterisation. The outputs and understandings from the geomorphic analysis of rivers undertaken in this study can support river management applications by explicitly incorporating understandings of river diversity and dynamics. This has the potential to reshape how river management is undertaken, to shift from reactive, engineering-based approaches that dominate in the Philippines, to more sustainable, ecosystem-based approaches to management.Department of Science and Technology—Philippine Council for Industry, Energy and Emerging Technology Research and Development (DOST-PCIEERD)—NERC Newton Fund grant (NE/S003312); Global Challenges Research Fund (SFC-GCRF) grant (2019)

Goals and principles for programmatic river restoration monitoring and evaluation: collaborative learning across multiple projects

River restoration is a relatively recent undertaking, with high levels of complexity and uncertainty involved. Many restoration projects have been monitored over the past three decades, however, results have rarely been compared across projects thereby limiting our ability to identify factors that influence restoration outcomes. Programmatic monitoring and evaluation (ProME) that builds on standardized surveys and systematic cross‐project comparison allows for collaborative learning, transfer of results across restoration projects and for adaptive management and monitoring. We present a conceptual framework for ProME consisting of four goals and nine principles. First, ProME accounts for complexity, uncertainty, and change in order to contribute to sustainable river management over the long term. Second, ProME promotes collaborative learning and adaptation by standardizing the sampling design for the field surveys at multiple projects and by disseminating findings across stakeholders. Third, ProME verifies to what extent restoration has been achieved, i.e., it must quantify the size and direction of change. Fourth, ProME identifies why the observed effects were present, thereby improving our mechanistic understanding of river functioning. We conclude with potential extensions of the framework (e.g., evaluating cumulative effects of projects within a catchment). Our conceptual framework presents a structured approach toward a more systematic learning and evidence‐based action in river restoration, while taking into account the wider picture of environmental change within which river restoration projects will inevitably operate

Classification of river morphology and hydrology to support management and restoration

The work leading to this paper has received funding from the European Union’s FP7 programme under Grant Agreement No. 282656 (REFORM

Extrinsic primary afferent signalling in the gut

Visceral sensory neurons activate reflex pathways that control gut function and also give rise to important sensations, such as fullness, bloating, nausea, discomfort, urgency and pain. Sensory neurons are organised into three distinct anatomical pathways to the central nervous system (vagal, thoracolumbar and lumbosacral). Although remarkable progress has been made in characterizing the roles of many ion channels, receptors and second messengers in visceral sensory neurons, the basic aim of understanding how many classes there are, and how they differ, has proven difficult to achieve. We suggest that just five structurally distinct types of sensory endings are present in the gut wall that account for essentially all of the primary afferent neurons in the three pathways. Each of these five major structural types of endings seems to show distinctive combinations of physiological responses. These types are: 'intraganglionic laminar' endings in myenteric ganglia; 'mucosal' endings located in the subepithelial layer; 'muscular–mucosal' afferents, with mechanosensitive endings close to the muscularis mucosae; 'intramuscular' endings, with endings within the smooth muscle layers; and 'vascular' afferents, with sensitive endings primarily on blood vessels. 'Silent' afferents might be a subset of inexcitable 'vascular' afferents, which can be switched on by inflammatory mediators. Extrinsic sensory neurons comprise an attractive focus for targeted therapeutic intervention in a range of gastrointestinal disorders.Australian National Health and Medical Research Counci

Yeast expressed recombinant Hemagglutinin protein of Novel H1N1 elicits neutralising antibodies in rabbits and mice

Currently available vaccines for the pandemic Influenza A (H1N1) 2009 produced in chicken eggs have serious impediments viz limited availability, risk of allergic reactions and the possible selection of sub-populations differing from the naturally occurring virus, whereas the cell culture derived vaccines are time consuming and may not meet the demands of rapid global vaccination required to combat the present/future pandemic. Hemagglutinin (HA) based subunit vaccine for H1N1 requires the HA protein in glycosylated form, which is impossible with the commonly used bacterial expression platform. Additionally, bacterial derived protein requires extensive purification and refolding steps for vaccine applications. For these reasons an alternative heterologous system for rapid, easy and economical production of Hemagglutinin protein in its glycosylated form is required. The HA gene of novel H1N1 A/California/04/2009 was engineered for expression in Pichia pastoris as a soluble secreted protein. The full length HA- synthetic gene having α-secretory tag was integrated into P. pastoris genome through homologous recombination. The resultant Pichia clones having multiple copy integrants of the transgene expressed full length HA protein in the culture supernatant. The Recombinant yeast derived H1N1 HA protein elicited neutralising antibodies both in mice and rabbits. The sera from immunised animals also exhibited Hemagglutination Inhibition (HI) activity. Considering the safety, reliability and also economic potential of Pichia expression platform, our preliminary data indicates the feasibility of using this system as an alternative for large-scale production of recombinant influenza HA protein in the face of influenza pandemic threat

Cytosolic 5'-nucleotidase 1A autoantibody profile and clinical characteristics in inclusion body myositis

OBJECTIVES: Autoantibodies directed against cytosolic 5'-nucleotidase 1A have been identified in many patients with inclusion body myositis. This retrospective study investigated the association between anticytosolic 5'-nucleotidase 1A antibody status and clinical, serological and histopathological features to explore the utility of this antibody to identify inclusion body myositis subgroups and to predict prognosis.MATERIALS AND METHODS: Data from various European inclusion body myositis registries were pooled. Anticytosolic 5'-nucleotidase 1A status was determined by an established ELISA technique. Cases were stratified according to antibody status and comparisons made. Survival and mobility aid requirement analyses were performed using Kaplan-Meier curves and Cox proportional hazards regression.RESULTS: Data from 311 patients were available for analysis; 102 (33%) had anticytosolic 5'-nucleotidase 1A antibodies. Antibody-positive patients had a higher adjusted mortality risk (HR 1.89, 95% CI 1.11 to 3.21, p=0.019), lower frequency of proximal upper limb weakness at disease onset (8% vs 23%, adjusted OR 0.29, 95% CI 0.12 to 0.68, p=0.005) and an increased prevalence of excess of cytochrome oxidase deficient fibres on muscle biopsy analysis (87% vs 72%, adjusted OR 2.80, 95% CI 1.17 to 6.66, p=0.020), compared with antibody-negative patients.INTERPRETATION: Differences were observed in clinical and histopathological features between anticytosolic 5'-nucleotidase 1A antibody positive and negative patients with inclusion body myositis, and antibody-positive patients had a higher adjusted mortality risk. Stratification of inclusion body myositis by anticytosolic 5'-nucleotidase 1A antibody status may be useful, potentially highlighting a distinct inclusion body myositis subtype with a more severe phenotype.</p