The dynamics of Southern Ocean storm tracks

The mechanisms that initiate and maintain oceanic "storm tracks" (regions of anomalously high eddy kinetic energy) are studied in a wind-driven, isopycnal, primitive equation model with idealized bottom topography. Storm tracks are found downstream of the topography in regions strongly influenced by a largescale stationary meander that is generated by the interaction between the background mean flow and the topography. In oceanic storm tracks the length scale of the stationary meander differs from that of the transient eddies, a point of distinction from the atmospheric storm tracks. When the zonal length and height of the topography are varied, the storm-track intensity is largely unchanged and the downstream storm-track length varies only weakly. The dynamics of the storm track in this idealized configuration are investigated using a wave activity flux (related to the Eliassen-Palmflux and eddy energy budgets). It is found that vertical fluxes of wave activity (which correspond to eddy growth by baroclinic conversion) are localized to the region influenced by the standing meander. Farther downstream, organized horizontal wave activity fluxes (which indicate eddy energy fluxes) are found. A mechanism for the development of oceanic storm tracks is proposed: the standing meander initiates localized conversion of energy from the mean field to the eddy field, while the storm track develops downstream of the initial baroclinic growth through the ageostrophic flux ofMontgomery potential. Finally, the implications of this analysis for the parameterization and prediction of storm tracks in ocean models are discussed

Improving the risk stratification, diagnosis and classification of patients with suspected myocardial infarction

Myocardial infarction is a leading cause of morbidity and mortality worldwide. The purpose of this thesis was to develop strategies for the assessment of patients with suspected myocardial infarction using a high-sensitivity cardiac troponin I assay, and to evaluate the relationship between the aetiology of myocardial infarction and long term clinical outcomes to identify opportunities to modify outcomes. In the United Kingdom, approximately 1 million patients present to hospital with chest pain each year and are assessed for suspected myocardial infarction, yet fewer than 20% of patients receive this diagnosis. Prior clinical standards mandated the admission of patients for serial cardiac troponin testing to identify myocardial necrosis and determine if myocardial infarction had occurred. However, new high-sensitivity assays offer a magnitude improvement in diagnostic precision, and as such provide a novel approach to diagnose or exclude myocardial infarction at an earlier stage. In our first study, I evaluate the performance of a high-sensitivity cardiac troponin I assay as a risk stratification tool in patients with suspected acute coronary syndrome. A systematic review and individual patient-level data meta-analysis was performed, including prospective studies measuring high-sensitivity cardiac troponin I in patients with suspected acute coronary syndrome, where the diagnosis was adjudicated according to the universal definition of myocardial infarction. The primary outcome was myocardial infarction or cardiac death during the index hospitalization or at 30 days. Meta-estimates for primary and secondary outcomes were derived using a binomial-normal random effects model. Performance was evaluated in subgroups and across a range of troponin concentrations (2-16 ng/L) using individual patient data. A total of 22,457 patients were included in the meta-analysis (age 62 [15.5] years; n=9,329 (41.5%) women), of whom 2,786 (12.4%) experienced myocardial infarction or cardiac death at 30 days. Cardiac troponin I concentrations were <5 ng/L at presentation in 11,012 (49%) patients, with a negative predictive value of 99.5% (95% confidence interval [CI] 99.3-99.6) for myocardial infarction or cardiac death at 30 days. Lower thresholds did not improve safety, but did significantly reduce the proportion identified as low risk. This threshold of 5 ng/L formed the basis for the development of a diagnostic pathway for patients with suspected acute coronary syndrome. In a cohort study of 1,218 patients with suspected acute coronary syndrome who underwent high-sensitivity cardiac troponin I measurement at presentation, 3 and 6 or 12 hours, I derived and validated a novel pathway (rule out myocardial infarction if <5 ng/L at presentation, or change <3 ng/L and <99th centile at 3 hours), and compared this with the established European Society of Cardiology 3-hour pathway (rule out myocardial infarction if <99th centile at presentation, or at 3 hours if symptoms <6 hours). The primary outcome was a comparison of the negative predictive value (NPV) of both pathways for myocardial infarction or cardiac death at 30 days. The primary outcome was evaluated in pre-specified subgroups stratified by age, gender, time of symptom onset and known ischaemic heart disease. In those <99th centile at presentation, the ESC pathway ruled out myocardial infarction in 28.1% (342/1,218) and 78.9% (961/1,218) at presentation and 3 hours respectively, missing 18 index and two 30-day events (NPV 97.9%, 95% confidence intervals [CI] 96.9-98.7%). The novel pathway ruled out 40.7% (496/1,218) and 74.2% (904/1,218) at presentation and 3 hours, missing two index and two 30-day events (NPV 99.5%, 95% CI 99.0-99.9%; P<0.001 for comparison). The NPV of the novel pathway was greater than the ESC pathway overall (P<0.001), and in all subgroups including those presenting early or known to have ischaemic heart disease. There are a number of additional approaches for the rule out of myocardial infarction. Clinical risk scores apply conventional risk factors to estimate the probability of myocardial infarction. The most widely implemented scores, HEART, EDACS, GRACE and TIMI, have been extensively validated when used alongside contemporary troponin assays, however, their impact on pathways applying high-sensitivity cardiac troponin testing is less clear. In 1,935 patients with suspected acute coronary syndrome, I evaluated the safety and efficacy of our novel pathway or the European Society of Cardiology 3-hour pathway alone, or in conjunction with low-risk TIMI (0 or 1), GRACE (≤108), EDACS (<16) or HEART (≤3) scores. Myocardial infarction or cardiac death at 30-days occurred in 14.3% (276/1,935). The ESC pathway ruled out 70% with 27 missed events giving a negative predictive value (NPV) of 97.9% (95% confidence interval [CI], 97.1 to 98.6%). Addition of a HEART score ≤3 reduced the proportion ruled out by the ESC pathway to 25%, but improved the NPV to 99.7% (95%CI 99.0 to 100%, P<0.001). The novel pathway ruled out 65% with three missed events for a NPV of 99.7% (95%CI 99.4 to 99.9%). No risk score improved the NPV, but all reduced the proportion ruled out (24-47%, P<0.001 for all). Whilst myocardial infarction due to atherosclerotic plaque rupture and thrombosis (type 1) is well described, the natural disease course of myocardial infarction due to oxygen supply-demand imbalance without atherothrombosis (type 2) is poorly understood. I aimed to define long-term outcomes and explore risk stratification in patients with type 2 myocardial infarction and myocardial injury. Consecutive patients (n=2,122) with elevated cardiac troponin I concentrations (≥0.05 μg/L) were identified at a tertiary cardiac centre. All diagnoses were adjudicated as per the Universal Definition of Myocardial Infarction. The primary outcome was all-cause death. Secondary outcomes included major adverse cardiovascular events (MACE; non-fatal myocardial infarction or cardiovascular death) and non-cardiovascular death. To explore competing risks, cause-specific hazard ratios were obtained using Cox regression models. The adjudicated index diagnosis was type 1 or type 2 myocardial infarction or myocardial injury in 1,171 (55.2%), 429 (20.2%) and 522 (24.6%) patients, respectively. At five years, all-cause death rates were higher in those with type 2 myocardial infarction (62.5%) or myocardial injury (72.4%) compared with type 1 myocardial infarction (36.7%). The majority of excess deaths in those with type 2 myocardial infarction or myocardial injury were due to non-cardiovascular causes (HR 2.32, 95%CI 1.92-2.81, versus type 1 myocardial infarction). Despite this, the observed crude MACE rates were similar between groups (30.6% versus 32.6%), with differences apparent after adjustment for co-variates (HR 0.82, 95%CI 0.69-0.96). Coronary heart disease was an independent predictor of MACE in those with type 2 myocardial infarction or myocardial injury (HR 1.71, 95%CI 1.31-2.24). Patients with type 2 myocardial infarction were less likely to receive secondary prevention therapy, suggesting a treatment gap may exist and there may be potential to modify clinical outcomes. A risk stratification threshold has been defined using high-sensitivity cardiac troponin I which identifies patients at very low risk of myocardial infarction or cardiac death. A diagnostic pathway incorporating this risk stratification threshold appears safer than established guidelines which apply the 99th centile alone. The use of clinical risk scores does not appear to improve the safety of this approach, however, does significantly reduce efficacy. Overall, these findings demonstrate the potential of high-sensitivity cardiac troponin testing to improve the efficiency of the assessment of patients with suspected acute coronary syndrome without compromising patient safety. The observations in those with myocardial injury and infarction have identified a phenotype of patients with type 2 myocardial infarction and coronary artery disease who are at increased cardiovascular risk, and who may benefit from targeted secondary prevention. The studies presented will inform the design of future clinical trials, and may inform international guidelines for the assessment of patients with suspected acute coronary syndrome

Non-volant modes of migration in terrestrial arthropods

Animal migration is often defined in terms appropriate only to the ‘to-and-fro’ movements of large, charismatic (and often vertebrate) species. However, like other important biological processes, the definition should apply over as broad a taxonomic range as possible in order to be intellectually satisfying. Here we illustrate the process of migration in insects and other terrestrial arthropods (e.g. arachnids, myriapods, and non-insect hexapods) but provide a different perspective by excluding the ‘typical’ mode of migration in insects, i.e. flapping flight. Instead, we review non-volant migratory movements, including: aerial migration by wingless species, pedestrian and waterborne migration, and phoresy. This reveals some fascinating and sometimes bizarre morphological and behavioural adaptations to facilitate movement. We also outline some innovative modelling approaches exploring the interactions between atmospheric transport processes and biological factors affecting the ‘dispersal kernels’ of wingless arthropods

Altered movement patterns but not muscle recruitment in moderately trained triathletes during running after cycling

Previous studies have shown that cycling can directly influence neuromuscular control during subsequent running in some highly trained triathletes, despite these triathletes\u27 years of practice of the cycle-run transition. The aim of this study was to determine whether cycling has the same direct influence on neuromuscular control during running in moderately trained triathletes. Fifteen moderately trained triathletes participated. Kinematics of the pelvis and lower limbs and recruitment of 11 leg and thigh muscles were compared between a control run (no prior exercise) and a 30 min run that was preceded by a 15 min cycle (transition run). Muscle recruitment was different between control and transition runs in only one of 15 triathletes (&lt;7%). Changes in joint position (mean difference of 3&deg;) were evident in five triathletes, which persisted beyond 5 min of running in one triathlete. Our findings suggest that some moderately trained triathletes have difficulty reproducing their pre-cycling movement patterns for running initially after cycling, but cycling appears to have little influence on running muscle recruitment in moderately trained triathletes. <br /

Aspirin desensitization in patients undergoing percutaneous coronary intervention: A survey of current practice

Background: Aspirin remains the mainstay of anti-platelet therapy in cardiac patients.However, if a patient is allergic to aspirin and dual anti-platelet therapy is indicated — suchas with percutaneous coronary intervention (PCI), then there is no clear guidance. Onepossibility is aspirin desensitization. A variety of protocols exist for the rapid desensitization ofpatients with aspirin allergy. The aim of this survey was to assess current knowledge andpractice regarding aspirin desensitization in the UK.Methods and results: We conducted a UK wide survey of all UK 116 PCI centers andobtained complete responses from 40 (35.4%) centers. Of these, just 7 (17.5%) centers hadpreviously desensitised patients; 29 (87.9%) centers suggested a lack of a local protocolprevented them from desensitizing, with 10 (30.3%) unsure of how to conduct desensitization.Only 5 (12.5%) centers had a local policy for aspirin desensitization although 25 (64.1%)units had a clinical strategy for dealing with aspirin allergy; the majority (72%) giving higherdoses of thienopyridine class drugs.Conclusions: In the UK, there appears to be no consistent approach to patients with aspirinallergy. Patients undergoing PCI benefit from dual anti-platelet therapy (including aspirin),and aspirin desensitization in those with known allergy may facilitate this. Sustained effortshould be placed on encouraging UK centers to use desensitization as a treatment modalityprior to PCI rather than avoiding aspirin altogether

Three coronary arteries arising from the right coronary cusp with a malignant sub-pulmonary course of the left anterior descending artery

AbstractWe describe a case of a 45-year-old man presenting with acute myocardial infarction investigated by computed tomography coronary angiography. Interestingly all three coronary arteries arose from the right coronary cusp. The left anterior descending artery (LAD) subtended an acute angle from the aortic root, associated with significant kinking and stenosis at the ostium, before passing anteriorly, taking a sub-pulmonic course and descending in the anterior interventricular groove. The distal vessel was small with an atrophic appearance. The circumflex artery followed a retro-aortic route, before trifurcating to supply the lateral and posterior walls of the left ventricle. The right coronary artery was normal. Given his unstable presentation and the potentially lethal course of the LAD, he was referred for grafting of the LAD vessel which successfully ameliorated his symptoms and has thus far prevented recurrent myocardial infarction.<Learning objective: Computed tomography coronary angiography is becoming increasingly accessible to physicians for the investigation of patients with suspected coronary disease and the planning of surgery. As such, coronary anomalies are likely to be encountered more frequently, and it is important to appreciate their clinical significance.