Search

Background: A traumatic Brachial Plexus Injury (BPI) involves major trauma to the large nerves of the arm, resulting in partial or complete paralysis, loss of feeling and unremitting pain. Outcome reporting in BPI research is inconsistent hindering synthesis of evidence to inform best care. This research aimed to develop a Core Outcome Set (COS) for adult BPI. Methods: Patient interviews and a systematic review of outcomes in BPI studies identified a long list of outcomes. Key stakeholders (surgeons, therapists and adults with a BPI) rated their importance in a 3 round international online Delphi on a 9-point Likert scale. During online patient and clinician consensus meetings the COS-BPI was determined. A systematic review was conducted to identify potential instruments available to measure the domains in the COS. Results: Sixty -four outcomes were identified from the systematic review and interviews. Seventy-two participants (21 people with a BPI, 20 surgeons and 31 therapists) from nineteen countries rated the importance of these outcomes in the online Delphi. Thirty-eight participants voted on 33 outcomes in the consensus meetings (25 clinicians and researchers and 13 people with the injury). Pain, voluntary movement and carrying out daily routine outcomes were included in the COS-BPI. A systematic review identified that the Brachial Assessment Tool (BrAT) and the Brief Pain Inventory could potentially measure the carrying out daily routine and pain outcomes in the COS-BPI. No suitable instrument to measure voluntary movement was identified. Conclusion: International consensus was reached on a COS for BPI which includes pain, voluntary movement and carrying out daily routine. The BrAT and Brief Pain Inventory can be used to measure the carrying out daily routine and pain domains. This will ensure that relevant outcomes are measured and reported and facilitate comparison across studies supporting BPI data synthesis to inform evidence-based practice.

Ocean chemistry has oscillated throughout Earth history to favour the dominant non-biogenic polymorph of calcium carbonate (CaCO3) to be either calcite or aragonite (Sandberg, 1983). Throughout the Phanerozoic these oscillations have occurred to facilitate aragonite-dominant conditions three times and calcite-dominant conditions twice. These aragonite-calcite seas conditions have previously been viewed as a global phenomenon where conditions fluctuate over time, but not in space, and represent the main environmental context in which the evolution of CaCO3 biomineralisation has occurred (Stanley and Hardie, 1998). CaCO3 is one of the most widely distributed minerals in the marine environment, occurring throughout geological history, both biogenically and non-biogenically (Lowenstam and Weiner, 1989). Marine non-biogenic precipitates are commonly found as carbonate ooids, sedimentary cements and muds (Nichols, 2009). Biogenic CaCO3 is formed via biomineralisation in calcifying organisms (Lowenstam and Weiner, 1989; Allemand et al., 2004), and is much more abundant than the non-biogenic forms. Although CaCO3 is abundant, it only accounts for a small proportion of the global carbon budget. Biogenic CaCO3 is representative of a larger proportion of the global carbon budget than non-biogenically formed CaCO3 (Berelson et al., 2007). The main driving force controlling the precipitation of CaCO3 polymorphs is the Mg:Ca molar ratio of seawater (Morse et al., 2007). However, other parameters such as temperature (Burton and Walter, 1984; Morse et al, 1997; Balthasar and Cusack, 2015), pCO2 (Lee and Morse, 2010), and SO4 (Morse et al., 2007) are also known to influence CaCO3 polymorph formation but are often overlooked in the context of aragonite-calcite seas. Fluctuations in these parameters of Mg:Ca ratio, SO42+ and pCO2 of seawater have been suggested to cause shifts in original composition of non-biogenic marine carbonates, and in turn viewed as the main driving mechanisms facilitating the switch between aragonite and calcite dominance (Morse et al., 1997; Lee and Morse, 2010; Bots et al., 2011). Specifically the influence of temperature is important because it is likely to result in aragonite-calcite sea conditions to vary spatially (Balthasar and Cusack, 2015). Today marine temperatures are changing across the latitudes due to environmental factors. Global CO2 levels have increased significantly since industrialisation (Doney et al., 2009), with 33% entering the oceans and reducing pH (Raven et al., 2005) accelerating climate change (IPCC, 2013) and influencing marine calcification (Fitzer et al., 2014a; 2015b; Bach, 2015; Zhao et al., 2017). Strong links between the carbon cycle and climate change observed in the rock record give evidence that environmental changes such as pCO2 and global warming have impacts on calcification and marine biota (Hönish et al., 2012). The first objective was to determine the influence of Mg:Ca ratio, temperature and water movement on the first-formed precipitates of non-biogenic CaCO3 precipitation yielded via a continuous addition technique experiments (Chapter 3). CaCO3 precipitation was induced by continuously adding bicarbonate to a bulk solution of known Mg:Ca ratio (1,2 or 3), and fixed salinity of 35 (practical salinity scale), at 20°C and 30ºC in still conditions, and then repeated with the solution being shaken at 80rpm mimicking more natural marine conditions. The mineralogy and crystal morphology of precipitates was determined using Raman Spectroscopy and Scanning Electron Microscopy. Results in Chapter 3 indicated that polymorphs co-precipitate, with the ratio of aragonite to calcite increasing with increased Mg:Ca ratio and elevated temperature. The main difference between still and shaken conditions was that overall, more crystals of aragonite compared to calcite precipitate in shaking conditions. The crystal size is less influenced in aragonite, but calcite crystals were smaller. These results contradict current views on aragonite-calcite seas as spatially homogenous ocean states need to be re-examined to include the effect of temperature on the spatial distribution of CaCO3 polymorphs. Examining polymorph growth under these experimental constraints allows us to gain a better understanding of how temperature and Mg:Ca together control non-biogenic aragonite and calcite precipitation providing a more realistic environmental framework in which to evaluate the evolution of biomineralisation. To further this work, the same continuous addition technique was used with the presence of sulphate in the mother solution (Chapter 4). Sulphate being the 4th most common marine ion (Halvey et al., 2012) and known to have an influence on mineralogy (Kontrec et al., 2004). The presence of sulphate increase the aragonite to calcite proportion formed compared to sulphate-free conditions (Chapter 4). Elevated temperature with sulphate further increased the proportion of aragonite to calcite facilitated (Chapter 4). In the presence of sulphate the main difference between sulphate-free environments and those with sulphate environments was: in still conditions the presence of sulphate increased the crystal number more than the crystal size at 20°C; at 30°C or in shaken conditions the presence of sulphate increased the crystal size of aragonite to calcite much more than it had influence on the crystal number. Non-biogenically the influence of sulphate lowered the threshold of Mg:Ca ratio that the switch between calcite and aragonite would be facilitated at (Bots et al., 2011). This would have implications for marine calcification as pure calcite seas would become very rare and imply that organisms would be forming calcified hard parts out with the supported mineralogies. Biogenic application of these results is complex however as organisms often have the ability to select aragonite as their main polymorph for their own functional requirements (Weiner and Dove, 2003). The growth parameters of non-biogenic polymorph formations grown from artificial seawater can be used to understand how organism control can influence the polymorph formation under similar conditions (Kawano et al., 2009). Assessing the elemental composition of mussel shells grown under know conditions of temperature and pCO2 allowed the environmental influences on mineralogy be assessed under possible the projected changes in climate forecast to occur by 2100 by IPCC (2013). Prior to this research, no study had used Mytilus edulis shell elemental composition to test the influence of aragonite-calcite sea conditions on mineralogy. This research compiles a detailed source of information on the constraints from environmental sources such as temperature and pCO2, on the elemental concentrations within shell formation and what potential changes could occur in response to a changing marine environment (Chapter 5). Here elevated temperature significantly increased the concentration of magnesium in calcite, but did not influence the magnesium concentration of aragonite unless combined with elevated pCO2. The concentrations of sulphur in calcite were significantly decreased at elevated pCO2 or combined increased temperature and pCO2 as concentrations of sodium were found to be increased under these conditions. In aragonite the concentrations of both sulphur and sodium were significantly different under all scenarios. Strontium did not yield any significant results in this research in either calcite or aragonite. Results observed indicate that the shell elemental concentrations are influenced differently in aragonite or calcite, and further influenced by environmental conditions based on the original mineralogy. This suggests that physiological mechanisms under the constraints of increased temperature and pCO2 can override the seawater chemistry influences of aragonite-calcite seas impacting on mineralogy. This research allows comparison of how non-biogenic and biogenic CaCO3 formation is influenced by seawater chemistry and environmental parameters to determine the dominant mineralogy. Increased temperature in both formations has shown to increase the impact of magnesium on calcite enabling the facilitation of aragonite. However, magnesium has influence on biogenic aragonite in extreme combined conditions of elevated temperature and pCO2. This work indicates that CaCO3 formation is complex and requires a multi-variable approach to understanding the mechanisms that facilitate the dominant mineralogy. By including variables such as temperature, this research suggests that aragonite-calcite seas conditions do not facilitate globally homogeneous switches in mineralogy, but the mineralogy is indeed influenced on latitudinal scales by other factors that influence the mechanisms involved.