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  • 1
    Language: English
    In: The Lancet, 22 September 2012, Vol.380(9847), pp.1099-1108
    Description: Most surgeons have adopted damage control surgery for severely injured patients, in which the initial operation is abbreviated after control of bleeding and contamination to allow ongoing resuscitation in the intensive-care unit. Developments in early resuscitation that emphasise rapid control of bleeding, restrictive volume replacement, and prevention or early management of coagulopathy are making definitive surgery during the first operation possible for many patients. Improved topical haemostatic agents and interventional radiology are becoming increasingly useful adjuncts to surgical control of bleeding. Better understanding of trauma-induced coagulopathy is paving the way for the replacement of blind, unguided protocols for blood component therapy with systemic treatments targeting specific deficiencies in coagulation. Similarly, treatments targeting dysregulated inflammatory responses to severe injury are under investigation. As point-of-care diagnostics become more suited to emergency environments, timely targeted intervention for haemorrhage control will result in better patient outcomes and reduced demand for blood products. Our Series paper describes how our understanding of the roles of the microcirculation, inflammation, and coagulation has shaped new and emerging treatment strategies.
    Keywords: Medicine
    ISSN: 0140-6736
    E-ISSN: 1474-547X
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  • 2
    In: Medical Journal of Australia, September 2013, Vol.199(5), pp.310-311
    Description: The dilemma that clinicians involved in the resuscitation of severely injured patients face with regards to the inclusion of tranexamic acid (TxA) in trauma management protocols is discussed. However, on the other hand, the need for more evidence to solve ongoing knowledge gaps has been emphasised, especially evidence of who benefits and whether anyone is harmed when TxA is administered to patients treated to modern civilian and military trauma standards.
    Keywords: Emergency Medicine
    ISSN: 0025-729X
    E-ISSN: 1326-5377
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  • 3
    Language: English
    In: The Lancet, 2011, Vol.377(9771), pp.1052-1054
    Description: Unlike coagulopathy that is secondary to haemodilution, hypothermia, or acidosis, acute traumatic coagulopathy is a hyperacute process in which systemic fibrinolysis releases D-dimers that are detectable within 30 min of injury.5 While the mechanisms are poorly understood, shock and tissue injury seem...
    Keywords: Medicine
    ISSN: 0140-6736
    E-ISSN: 1474-547X
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  • 4
    Language: English
    In: BMJ: British Medical Journal, 24 November 2012, Vol.345(7884), pp.46-47
    Description: KEY POINTS Give tranexamic acid to trauma patients at risk of major haemorrhage as early as possible, but not at all if three hours have passed since injury Incorporate tranexamic acid into protocols for prehospital trauma care where feasible Seekfurther evidence, including mechanistic studies and confirmatory trials of benefits and potential harms in advanced trauma systems
    Keywords: Medicine;
    ISSN: 09598138
    E-ISSN: 17561833
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  • 5
    Language: English
    In: Journal of Biomechanics, 15 March 2013, Vol.46(5), pp.949-955
    Description: Stem–cement and cement–bone interfacial failures as well as cement fractures have been noted in cemented total hip arthroplasty (THA) as the cause of aseptic loosening. Attempts to reduce the risk of femoral component loosening include improving the stem–cement interface by various coatings, using a textured or porous coated stem surfaces or by using a tapered stem having a highly-polished surface. The latter approach, often referred to as “force-closed” femoral stem design, would theoretically result in stem stabilization subsequent to debonding and ‘taper-lock’. Previous work using three-dimensional finite element analysis has shown a state of stress at the stem–cement interface indicative of ‘taper-lock’ for the debonded stem and indicated that stem–cement interface friction and bone cement creep played a significant role in the magnitudes of stresses and subsidence of the stem. However, the previous analysis did not include the viscoelastic properties of bone, which has been hypothesized to permit additional expansion of the bone canal and allow additional stem subsidence ( ). The goal of this study was to investigate the effect of bone viscoelastic behavior on stem subsidence using a 3D finite element analysis. It was hypothesized that the viscoelastic behavior of bone in the hoop direction would allow expansion of the bone reducing the constraint on bone over time and permit additional stem subsidence, which may account for the discrepancies between predicted and clinical subsidence measurements. Analyses were conducted using physiological loads, ‘average peak loads’ and ‘high peak loads’ for ‘normal patient’ and ‘active patient’ ( ) from which short and long term subsidence was predicted. Results indicated that bone creep does contribute to higher stem subsidence initially and after 10 years of simulated loading. However, it was concluded that the “constraint” upon the cement mantle is not mitigated enough to result in stem subsidence equivalent to that observed clinically.
    Keywords: Cemented Total Hip Arthroplasty ; Cortical Bone Creep ; Bone Cement Creep ; Stem Subsidence ; Stem–Cement Interface Failure ; Medicine ; Engineering ; Anatomy & Physiology
    ISSN: 0021-9290
    E-ISSN: 1873-2380
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  • 6
    Language: English
    In: The Lancet, 22 September 2012, Vol.380(9847), pp.1033-1034
    Description: By 2030, road traffic injuries are predicted to be the world's fifth leading cause of death and the third leading cause of disability.1 The Lancet's accompanying Series on trauma surgery updates present knowledge of three broad aspects of acute trauma care: haemorrhagic shock (responsible for most preventable trauma deaths),2 traumatic brain injury (the cause of most trauma-related deaths in developed trauma systems),3 and major musculoskeletal injury (the reason for most operations and the cause of much disability).4 The Series reveals substantial progress in the understanding of genomic, proteomic, and physiological changes that begin within seconds or minutes of severe injury, are affected by resuscitation and surgery, and are strongly associated with patient outcomes. The Series points to some promising topics in brain injury, fracture healing, coagulopathy, and the immune-inflammatory response to severe injury. Because studies of monotherapies to target discrete mechanisms have often yielded disappointing results, future clinical studies should explore broad-acting therapeutic strategies and treatment combinations.
    Keywords: Medicine
    ISSN: 0140-6736
    E-ISSN: 1474-547X
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  • 7
    Language: English
    In: The Lancet, 22 September 2012, Vol.380(9847), pp.1088-1098
    Description: Severe traumatic brain injury remains a major health-care problem worldwide. Although major progress has been made in understanding of the pathophysiology of this injury, this has not yet led to substantial improvements in outcome. In this report, we address present knowledge and its limitations, research innovations, and clinical implications. Improved outcomes for patients with severe traumatic brain injury could result from progress in pharmacological and other treatments, neural repair and regeneration, optimisation of surgical indications and techniques, and combination and individually targeted treatments. Expanded classification of traumatic brain injury and innovations in research design will underpin these advances. We are optimistic that further gains in outcome for patients with severe traumatic brain injury will be achieved in the next decade.
    Keywords: Medicine
    ISSN: 0140-6736
    E-ISSN: 1474-547X
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  • 8
    Language: English
    In: The Journal of Pediatrics, April 2013, Vol.162(4), pp.713-718.e2
    Description: To investigate whether prenatal exposure to nicotine has an impact on several reading skill outcomes in school age children. Using a longitudinal sample of 5119 school age children in the Avon Longitudinal Study of Parents and Children, this study investigated specific reading skill outcomes in the area of speed, fluency, accuracy, spelling, and comprehension in relation to prenatal nicotine exposure, after adjusting for potential mediators and confounders. Prenatal nicotine exposure was divided into 3 categories: high (〉17 mg per day), low (≤17 mg per day), and no exposure. We found that prenatal nicotine exposure was associated with increased risk of underperformance in specific reading skill outcomes after adjusting for potential mediators and confounders ( = .006). The effect of poor performance in decoding single words was most pronounced among children with prenatal exposure to high levels of nicotine in conjunction with a phonological deficit. Overall, the results showed that maternal smoking has moderate to large associations with delayed or decreased reading skills of children in the Longitudinal Study of Parents and Children. High prenatal nicotine exposure has a negative association with reading performance in school age children. In addition, modeling showed that environmental factors significantly moderated the interaction between prenatal nicotine exposure and reading skill outcomes.
    Keywords: Medicine
    ISSN: 0022-3476
    E-ISSN: 1097-6833
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  • 9
    Language: English
    In: Biomaterials, November 2012, Vol.33(32), pp.8160-8166
    Description: The delivery of nucleic acids such as plasmid DNA and siRNA into cells is a cornerstone of biological research and is of fundamental importance for medical therapeutics. Although most gene delivery therapeutics in clinical trials are based on viral vectors, safety issues remain a major concern. Non-viral vectors, such as cationic lipids and polymers, offer safer alternatives but their gene delivery efficiencies are usually not high enough for clinical applications. Thus, there is a high demand for more efficient and safe non-viral vectors. Here, we present a facile two-step method based on thiol-yne click chemistry for parallel synthesis of libraries of new biomimetic cationic thioether lipids. A library of novel lipids was synthesized using the developed method and more than 10% of the lipids showed highly efficient transfection in different cell types, surpassing the efficiency of several popular commercial transfection reagents. One of the new lipids showed highly efficient siRNA delivery to multiple cell types and could successfully deliver DNA plasmid to difficult-to-transfect mouse embryonic stem cells (mESC). Analysis of structure–activity relationship revealed that the length of the hydrophobic alkyl groups was a key parameter for efficient cell transfection and was more important for transfection efficiency than the nature of cationic head groups. The correlation of the size and surface charge of liposomes with transfection efficiency is described.
    Keywords: Thiol-Yne Chemistry ; Cationic Lipid ; Gene Delivery ; Biomimetic Lipid ; Medicine ; Engineering
    ISSN: 0142-9612
    E-ISSN: 1878-5905
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  • 10
    Language: English
    In: Intensive Care Medicine, 2016, Vol.42(1), pp.3-15
    Description: INTRODUCTIONThe Glasgow Coma Scale (GCS) provides a structured method for assessment of the level of consciousness. Its derived sum score is applied in research and adopted in intensive care unit scoring systems. Controversy exists on the reliability of the GCS. The aim of this systematic review was to summarize evidence on the reliability of the GCS. METHODSA literature search was undertaken in MEDLINE, EMBASE and CINAHL. Observational studies that assessed the reliability of the GCS, expressed by a statistical measure, were included. Methodological quality was evaluated with the consensus-based standards for the selection of health measurement instruments checklist and its influence on results considered. Reliability estimates were synthesized narratively. RESULTSWe identified 52 relevant studies that showed significant heterogeneity in the type of reliability estimates used, patients studied, setting and characteristics of observers. Methodological quality was good (n = 7), fair (n = 18) or poor (n = 27). In good quality studies, kappa values were ≥0.6 in 85%, and all intraclass correlation coefficients indicated excellent reliability. Poor quality studies showed lower reliability estimates. Reliability for the GCS components was higher than for the sum score. Factors that may influence reliability include education and training, the level of consciousness and type of stimuli used. CONCLUSIONSOnly 13% of studies were of good quality and inconsistency in reported reliability estimates was found. Although the reliability was adequate in good quality studies, further improvement is desirable. From a methodological perspective, the quality of reliability studies needs to be improved. From a clinical perspective, a renewed focus on training/education and standardization of assessment is required.
    Keywords: Glasgow Coma Scale ; Glasgow Coma Score ; Grading scales ; Reliability ; Reproducibility of results ; Systematic review
    ISSN: 0342-4642
    E-ISSN: 1432-1238
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