Anaemia, Iron-Deficiency and Reducing Transfusion in Cardiac Surgery and A Novel Method for the Measurement of Total Haemoglobin Mass

Anaemia and iron-deficiency are common in cardiac surgical patients and are associated with poor surgical and patient-centred outcomes. Pre-operative anaemia is increasingly being treated with intravenous iron despite a lack of high-quality evidence of its effectiveness. This thesis explores these topics with a literature review exploring anaemia, iron-deficiency, and transfusion in cardiac surgery, and further review on transfusion risk-prediction models, and treatment of pre-operative anaemia with intravenous iron. The first methodological chapter describes the development of a new risk-scoring system to predict those who are likely to require peri-operative red blood cell transfusion in cardiac surgical patients in the UK. This risk scoring system was then modified and recalibrated using an Australian database to create an alternative score applicable to that population, described in the subsequent chapter. The use of intravenous iron has increased significantly since the introduction of new iron-preparations and is now recommended in many treatment pathways and guidelines. This has occurred in advance of high-quality evidence that it can effectively treat anaemia in the pre-operative period and have any meaningful effect on patient outcomes. Chapter 5 describes a UK-wide multicentre trial that demonstrated that IV iron can significantly increase haemoglobin concentration in cardiac surgical patients in the pre-operative period. Challenges in the recruitment for larger studies of anaemic cardiac surgical patients led to an exploration of the recent trends in anaemia-rates over the last 5-7 years, which is described in Chapter 6. This demonstrates that anaemia rates in certain areas have decreased significantly over that period and there has been concomitant exponential increase in the use of intravenous iron preparations in various medical settings. The final methodological chapter describes a novel method for measuring total haemoglobin mass, which may be a more appropriate method of assessing anaemia in various disease states. Previous methods have been difficult to establish and complicated to undertake. This chapter describes a new method using a modification of an existing respiratory function test which is demonstrated to be a simple method of estimating total haemoglobin mass and plasma volume

Hurricane Sandy Effects on Coastal Marsh Elevation Change

High-magnitude storm events such as Hurricane Sandy are powerful agents of geomorphic change in coastal marshes, potentially altering their surface elevation trajectories. But how do a storm’s impacts vary across a large region spanning a variety of wetland settings and storm exposures and intensities. We determined the short-term impacts of Hurricane Sandy at 223 surface elevation table–marker horizon stations in estuarine marshes located across the northeast region of the United States by comparing post- storm surface elevation change with pre-storm elevation trends. We hypothesized that the storm’s effect on marsh elevation trends would be influenced by position relative to landfall (right or left) and distance from landfall. The structural equation model presented predicts that marshes located to the left of landfall were more likely to experience an elevation gain greater than expected, and this positive deviation from pre-storm elevation trends tended to have a greater magnitude than those experiencing negative deviations (elevation loss), potentially due to greater sediment deposition. The magnitude of negative deviations from elevation change in marshes to the right of landfall was greater than for positive deviations, with a greater effect in marshes within 200 km of landfall, potentially from the extent and magnitude of storm surge. Overall, results provide an integrated picture of how storm characteristics combined with the local wetland setting are important to a storm’s impact on surface elevation, and that the surface elevation response can vary widely among sites across a region impacted by the same storm

An orthogonal C-H borylation - cross-coupling strategy for the preparation of tetrasubstituted "A(2)B(2)''-chrysene derivatives with tuneable photophysical properties

Cl-substituents serve as a functionalisable regiocontrol element for the orthogonal functionalisation of chrysene.</p

A One Medicine Mission for an Effective Rabies Therapy

Despite the disease's long history, little progress has been made toward a treatment for rabies. The prognosis for patient recovery remains dire. For any prospect of survival, patients require aggressive critical care, which physicians in rabies endemic areas may be reluctant or unable to provide given the cost, clinical expertise required, and uncertain outcome. Systematic clinical research into combination therapies is further hampered by sporadic occurrence of cases. In this Perspective, we examine the case for a One Medicine approach to accelerate development of an effective therapy for rabies through the veterinary care and investigational treatment of naturally infected dogs in appropriate circumstances. We review the pathogenesis of rabies virus in humans and dogs, including recent advances in our understanding of the molecular basis for the severe neurological dysfunction. We propose that four categories of disease process need to be managed in patients: viral propagation, neuronal degeneration, inflammation and systemic compromise. Compassionate critical care and investigational treatment of naturally infected dogs receiving supportive therapy that mimics the human clinical scenario could increase opportunities to study combination therapies that address these processes, and to identify biomarkers for prognosis and therapeutic response. We discuss the safety and ethics of this approach, and introduce the Canine Rabies Treatment Initiative, a non-profit organization with the mission to apply a One Medicine approach to the investigation of diagnostic, prognostic, and therapeutic options for rabies in naturally infected dogs, to accelerate transformation of rabies into a treatable disease for all patients

Entomo-venomics: the evolution, biology and biochemistry of insect venoms

The insects are a hyperdiverse class containing more species than all other animal groups combined-many of which employ venom to capture prey, deter predators and micro-organisms, or facilitate parasitism or extra-oral digestion. However, with the exception of those made by Hymenoptera (wasps, ants and bees), little is known about insect venoms. Here, we review the current literature on insects that use venom for prey capture and predator deterrence, finding evidence for fourteen independent origins of venom usage among insects, mostly among the hyperdiverse holometabolan orders. Many lineages, including the True Bugs (Heteroptera), robber flies (Asilidae), and larvae of many Neuroptera, Coleoptera and Diptera, use mouthpart-associated venoms to paralyse and pre-digest prey during hunting. In contrast, some Hymenoptera and larval Lepidoptera, and one species of beetle, use non-mouthpart structures to inject venom in order to cause pain to deter potential predators. Several recently published insect venom proteomes indicate molecular convergence between insects and other venomous animal groups, with all insect venoms studied so far being potently bioactive cocktails containing both peptides and larger proteins, including novel peptide and protein families. This review summarises the current state of the field of entomo-venomics