Microscopic Optical Trapping of Ultracold Neutral Atoms for Applications in Quantum Information

In this thesis, the development of an experimental system for microscopic dipole trapping of ultracold neutral rubidium atoms is presented. The purpose of this system is to advance towards the experimental realisation of a quantum computational protocol utilising neutral atoms as qubits. It is intended that the quantum gate operations between qubits will be implemented by a scheme using Rydberg blockade, imposing a restriction on the maximum size of the dipole-trapped atom cloud; the spatial extent of the atomic ensemble contained in this trap must be smaller than the blockade radius to ensure that one single collective Rydberg state per qubit can be achieved. Therefore the experiment was designed with the intent of fulfilling these challenging requirements. This project involved the design and construction of an improved ultra-high vacuum chamber containing the optical setup for the experiment, successfully achieving pressures below 5 x 10-10 mbar. A magneto-optical trap was produced to act as a background reservoir of atoms from which to load the dipole trap. Numerous experimental measurements were done to characterise the physical properties of the trapped atoms, including the number, density and temperature of atoms, as well as the lifetime of the trap. The results of these measurements led to the conclusion that a suitable reservoir for loading the dipole trap had been produced. Significant work was carried out to set up and obtain the dipole trap in the laboratory. Measurements of the characteristic properties of the trap and the atoms confined in the trap were carried out to investigate the behaviour of the atoms and to validate our design. Ultimately a trap containing tens of atoms was achieved, with an atom cloud diameter of ~1.2 µm in two dimensions, being well within the estimated Rydberg blockade radius of ~4.4 µm for n ~ 60 as intended. The two-photon excitation laser system for the probing of Rydberg states, for future applications in Rydberg blockade-based quantum gate operations, was also developed during the course of this work. Different Rydberg states were detected experimentally by the observation of Autler-Townes splitting in a three-level atom scheme. Overall, the work presented in this thesis provides a strong groundwork for the advancement towards neutral atom-based quantum gates, including the development of the experimental system and the production of standard procedures to carry out characterisation measurements of the traps efficiently in the future. The main achievements of this work are the establishment of the experimental apparatus, the achievement of a microscopic dipole trap which conforms to the requirements of an atomic qubit, and the significant growth in the knowledge of atom trapping specific to our system

Radiation-responsive miRNAs predicted by miRStress are biologically relevant.

<p>A: The miRNAs which are most frequently deregulated following radiation stress, as reported by miRStress, were used to ‘predict’ radiation-responsive pathways, as described in the methods. Control pathways were selected by using a list of control miRNAs. These were then compared to a list of KEGG pathways which are observed (as opposed to predicted) to actually change following radiation (in a total of 18 datasets). The average frequency with which the predicted control or radiation pathways appears in the observed pathways is shown. On average the radiation predicted-pathways are more frequently present in the observed pathways (t test, p 0.002). In other words, the radiation miRNAs are predicted to target pathways which actually change following radiation. Error bars show standard error of the mean for 20 (for radiation) and 21 (for control) pathways. B: Radiation and control miRNAs used in part A were used to test for correlations between SF5 (surviving fraction of cells following a 5 Gray radiation dose) and miRNA level across the NCI-60 panel. A Pearson correlation was obtained for each radiation and control miRNA (not all were available on the microarray platform). The average Pearson correlation value (see methods) for the control and radiation miRNAs is shown. The radiation miRNAs have a significantly higher correlation with radiosensitivity compared to the control miRNAs (t test, p = 0.02). </p

Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI) : a phase 3, placebo-controlled, randomised trial

Background: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. Methods: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). Findings: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3·3 years (IQR 2·8–3·8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7·3%] of 5558 vs 480 [8·6%] of 5596; HR 0·85 [95% CI 0·74–0·97], p=0·013). The same effect was not observed in patients without PCI (p=0·76, p interaction=0·16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3·1%] with ticagrelor vs 183 (3·3%) with placebo; HR 0·96 [95% CI 0·78–1·18], p=0·68), as well as all-cause death (282 [5·1%] vs 323 [5·8%]; 0·88 [0·75–1·03], p=0·11). TIMI major bleeding occurred in 111 (2·0%) of 5536 patients receiving ticagrelor and 62 (1·1%) of 5564 patients receiving placebo (HR 2·03 [95% CI 1·48–2·76], p<0·0001), and fatal bleeding in 6 (0·1%) of 5536 patients with ticagrelor and 6 (0·1%) of 5564 with placebo (1·13 [0·36–3·50], p=0·83). Intracranial haemorrhage occurred in 33 (0·6%) and 31 (0·6%) patients (1·21 [0·74–1·97], p=0·45). Ticagrelor improved net clinical benefit: 519/5558 (9·3%) versus 617/5596 (11·0%), HR=0·85, 95% CI 0·75–0·95, p=0·005, in contrast to patients without PCI where it did not, p interaction=0·012. Benefit was present irrespective of time from most recent PCI. Interpretation: In patients with diabetes, stable coronary artery disease, and previous PCI, ticagrelor added to aspirin reduced cardiovascular death, myocardial infarction, and stroke, although with increased major bleeding. In that large, easily identified population, ticagrelor provided a favourable net clinical benefit (more than in patients without history of PCI). This effect shows that long-term therapy with ticagrelor in addition to aspirin should be considered in patients with diabetes and a history of PCI who have tolerated antiplatelet therapy, have high ischaemic risk, and low bleeding risk

The surgical safety checklist and patient outcomes after surgery: a prospective observational cohort study, systematic review and meta-analysis

© 2017 British Journal of Anaesthesia Background: The surgical safety checklist is widely used to improve the quality of perioperative care. However, clinicians continue to debate the clinical effectiveness of this tool. Methods: Prospective analysis of data from the International Surgical Outcomes Study (ISOS), an international observational study of elective in-patient surgery, accompanied by a systematic review and meta-analysis of published literature. The exposure was surgical safety checklist use. The primary outcome was in-hospital mortality and the secondary outcome was postoperative complications. In the ISOS cohort, a multivariable multi-level generalized linear model was used to test associations. To further contextualise these findings, we included the results from the ISOS cohort in a meta-analysis. Results are reported as odds ratios (OR) with 95% confidence intervals. Results: We included 44 814 patients from 497 hospitals in 27 countries in the ISOS analysis. There were 40 245 (89.8%) patients exposed to the checklist, whilst 7508 (16.8%) sustained ≥1 postoperative complications and 207 (0.5%) died before hospital discharge. Checklist exposure was associated with reduced mortality [odds ratio (OR) 0.49 (0.32–0.77); P\u3c0.01], but no difference in complication rates [OR 1.02 (0.88–1.19); P=0.75]. In a systematic review, we screened 3732 records and identified 11 eligible studies of 453 292 patients including the ISOS cohort. Checklist exposure was associated with both reduced postoperative mortality [OR 0.75 (0.62–0.92); P\u3c0.01; I2=87%] and reduced complication rates [OR 0.73 (0.61–0.88); P\u3c0.01; I2=89%). Conclusions: Patients exposed to a surgical safety checklist experience better postoperative outcomes, but this could simply reflect wider quality of care in hospitals where checklist use is routine

Prospective observational cohort study on grading the severity of postoperative complications in global surgery research

Background The Clavien–Dindo classification is perhaps the most widely used approach for reporting postoperative complications in clinical trials. This system classifies complication severity by the treatment provided. However, it is unclear whether the Clavien–Dindo system can be used internationally in studies across differing healthcare systems in high- (HICs) and low- and middle-income countries (LMICs). Methods This was a secondary analysis of the International Surgical Outcomes Study (ISOS), a prospective observational cohort study of elective surgery in adults. Data collection occurred over a 7-day period. Severity of complications was graded using Clavien–Dindo and the simpler ISOS grading (mild, moderate or severe, based on guided investigator judgement). Severity grading was compared using the intraclass correlation coefficient (ICC). Data are presented as frequencies and ICC values (with 95 per cent c.i.). The analysis was stratified by income status of the country, comparing HICs with LMICs. Results A total of 44 814 patients were recruited from 474 hospitals in 27 countries (19 HICs and 8 LMICs). Some 7508 patients (16·8 per cent) experienced at least one postoperative complication, equivalent to 11 664 complications in total. Using the ISOS classification, 5504 of 11 664 complications (47·2 per cent) were graded as mild, 4244 (36·4 per cent) as moderate and 1916 (16·4 per cent) as severe. Using Clavien–Dindo, 6781 of 11 664 complications (58·1 per cent) were graded as I or II, 1740 (14·9 per cent) as III, 2408 (20·6 per cent) as IV and 735 (6·3 per cent) as V. Agreement between classification systems was poor overall (ICC 0·41, 95 per cent c.i. 0·20 to 0·55), and in LMICs (ICC 0·23, 0·05 to 0·38) and HICs (ICC 0·46, 0·25 to 0·59). Conclusion Caution is recommended when using a treatment approach to grade complications in global surgery studies, as this may introduce bias unintentionally