A computational framework for modelling micro-scale fluids in the presence of surface tension

Immunisation, pioneered by Edward Jenner (1749-1823), has saved millions of lives and has helped the human race survive several disease pandemics. Today, the immunisation industry conducts vast amounts of research, not only developing new vaccinations, but also new methods of diagnosis. Currently, blood samples are taken manually using a syringe, loaded into a centrifuge and spun for several hours to separate out the different parts of the blood sample. These parts can then be tested manually for a range of ailments. In some areas of the world, access to such a device is unavailable and even if it was, this can be a long, energy intensive and costly process. Hence, new faster methods involving the use of microchips and surface acoustic waves and are an inviting possibility. Utilising the field of fluid dynamics, notably the work of Newton, Euler, Cauchy, Navier and Stokes, combined with modern computational methods allows for an engineering perspective to be taken on this problem. This thesis combines many novel contributions to create a computational modelling framework to model external excitation of axisymmetric micro-scale fluid droplets. In the present work fluid motion is governed by an axisymmetric form of the Navier-Stokes equations, with focus on incompressible Newtonian fluids, and this is presented in full. At the micro-scale, surface tension is the most dominant force, hence additional contributions are derived and included due to surface tension and contact line forces. Additionally, to reduce spurious oscillations within the pressure field, the pressure Laplacian stabilisation (PLS) technique is implemented. A derivation of the technique as well as an investigation into the effect of the stabilisation parameter is presented. The kinematics of the system are of great importance. At the micro-scale, tracking of the surface of the fluid is highly desirable and most advantageous, and the choice of kinematic description must reflect this. Unlike more traditional computational methods adopting an Eulerian description or a Lagrangian description of the governing equations, the presented computational framework makes use of the Arbitrary Lagrangian Eulerian (ALE) description. The ALE formulation avoids many of the drawbacks of traditional methods whilst allowing for accurate tracking of the fluid surface and minimising the requirement for frequent remeshing. Taking the current, deformed, configuration as the reference configuration in an Updated Lagrangian (UL) manner, combines into a kinematic description termed the Updated Arbitrary Lagrangian Eulerian (UALE) formulation. The physics underlying this formulation are presented in detail within this thesis. Several problems, examining a range of droplet volume, contact angle and experimental configuration are presented to validate the computational framework against analytical solutions. Of the various problems examined, all show a very good correlation to analytical solutions. Differences, if any, are attributed to the density of the mesh, which is shown to alter the amplitude but not the frequency of oscillation, or over-simplification made in the analytical solutions. Lastly, a new hypothesis is tested which until recently was extremely difficult to verify. The current hypothesis in the literature proposes that upon reaching the fluid-solid inter- face, surface acoustic waves propagate through the fluid causing motion. Conversely, the new hypothesis proposes that upon reaching the fluid-solid interface, surface acoustic waves propagate capillary waves up the surface of the droplet, changing the apparent wetting angle and inducing motion. This is implemented by changing the contact angle in time to simulate the action of surface acoustic waves and the resulting analysis recorded the occurrence of jetting thereby confirming the hypothesis. Further testing can be conducted and this technology utilised in the development of new disease diagnosis devices. The computational framework has been very successful in modelling a range of micro-scale problems. Further development of this framework will allow for a greater understanding of the effect of surface acoustic waves on a fluid droplet. In turn, this will allow for the improved design of surface acoustic wave devices

Completion Dissection or Observation for Sentinel-Node Metastasis in Melanoma.

Sentinel-lymph-node biopsy is associated with increased melanoma-specific survival (i.e., survival until death from melanoma) among patients with node-positive intermediate-thickness melanomas (1.2 to 3.5 mm). The value of completion lymph-node dissection for patients with sentinel-node metastases is not clear. In an international trial, we randomly assigned patients with sentinel-node metastases detected by means of standard pathological assessment or a multimarker molecular assay to immediate completion lymph-node dissection (dissection group) or nodal observation with ultrasonography (observation group). The primary end point was melanoma-specific survival. Secondary end points included disease-free survival and the cumulative rate of nonsentinel-node metastasis. Immediate completion lymph-node dissection was not associated with increased melanoma-specific survival among 1934 patients with data that could be evaluated in an intention-to-treat analysis or among 1755 patients in the per-protocol analysis. In the per-protocol analysis, the mean (±SE) 3-year rate of melanoma-specific survival was similar in the dissection group and the observation group (86±1.3% and 86±1.2%, respectively; P=0.42 by the log-rank test) at a median follow-up of 43 months. The rate of disease-free survival was slightly higher in the dissection group than in the observation group (68±1.7% and 63±1.7%, respectively; P=0.05 by the log-rank test) at 3 years, based on an increased rate of disease control in the regional nodes at 3 years (92±1.0% vs. 77±1.5%; P<0.001 by the log-rank test); these results must be interpreted with caution. Nonsentinel-node metastases, identified in 11.5% of the patients in the dissection group, were a strong, independent prognostic factor for recurrence (hazard ratio, 1.78; P=0.005). Lymphedema was observed in 24.1% of the patients in the dissection group and in 6.3% of those in the observation group. Immediate completion lymph-node dissection increased the rate of regional disease control and provided prognostic information but did not increase melanoma-specific survival among patients with melanoma and sentinel-node metastases. (Funded by the National Cancer Institute and others; MSLT-II ClinicalTrials.gov number, NCT00297895 .)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

A review of the impacts of tobacco industry privatisation: Implications for policy.

State-owned tobacco companies, which still account for 40% of global cigarette production, face continued pressure from, among others, the International Monetary Fund (IMF), to be privatised. This review of available literature on tobacco industry privatisation suggests that any economic benefits of privatisation may be lower than supposed, because private owners avoid competitive tenders (thus underpaying for assets), negotiate lengthy tax holidays and are complicit in the smuggling of cigarettes to avoid import and excise duties. It outlines how privatisation leads to increased marketing, more effective distribution and lower prices, creating additional demand for cigarettes among new and existing smokers, leading to increased cigarette consumption, higher smoking prevalence and lower age of smoking initiation. Privatisation also weakens tobacco control because private owners, in their drive for profits, lobby aggressively against effective policies and ignore or overturn existing policies. This evidence suggests that further tobacco industry privatisation is likely to increase smoking and that instead of transferring assets from state to private ownership, alternative models of supply should be explored

Therapeutic Value of Sentinel Lymph Node Biopsy in Patients With Melanoma: A Randomized Clinical Trial.

Sentinel lymph node (SLN) biopsy is a standard staging procedure for cutaneous melanoma. Regional disease control is a clinically important therapeutic goal of surgical intervention, including nodal surgery. To determine how frequently SLN biopsy without completion lymph node dissection (CLND) results in long-term regional nodal disease control in patients with SLN metastases. The second Multicenter Selective Lymphadenectomy Trial (MSLT-II), a prospective multicenter randomized clinical trial, randomized participants with SLN metastases to either CLND or nodal observation. The current analysis examines observation patients with regard to regional nodal recurrence. Trial patients were aged 18 to 75 years with melanoma metastatic to SLN(s). Data were collected from December 2004 to April 2019, and data were analyzed from July 2020 to January 2022. Nodal observation with ultrasonography rather than CLND. In-basin nodal recurrence. Of 823 included patients, 479 (58.2%) were male, and the mean (SD) age was 52.8 (13.8) years. Among 855 observed basins, at 10 years, 80.2% (actuarial; 95% CI, 77-83) of basins were free of nodal recurrence. By univariable analysis, freedom from regional nodal recurrence was associated with age younger than 50 years (hazard ratio [HR], 0.49; 95% CI, 0.34-0.70; P &lt; .001), nonulcerated melanoma (HR, 0.36; 95% CI, 0.36-0.49; P &lt; .001), thinner primary melanoma (less than 1.5 mm; HR, 0.46; 95% CI, 0.27-0.78; P = .004), axillary basin (HR, 0.61; 95% CI, 0.44-0.86; P = .005), fewer positive SLNs (1 vs 3 or more; HR, 0.32; 95% CI, 0.14-0.75; P = .008), and SLN tumor burden (measured by diameter less than 1 mm [HR, 0.39; 95% CI, 0.26-0.60; P = .001] or less than 5% area [HR, 0.36; 95% CI, 0.24-0.54; P &lt; .001]). By multivariable analysis, younger age (HR, 0.57; 95% CI, 0.39-0.84; P = .004), thinner primary melanoma (HR, 0.40; 95% CI, 0.22-0.70; P = .002), axillary basin (HR, 0.55; 95% CI, 0.31-0.96; P = .03), SLN metastasis diameter less than 1 mm (HR, 0.52; 95% CI, 0.33-0.81; P = .007), and area less than 5% (HR, 0.58; 95% CI, 0.38-0.88; P = .01) were associated with basin control. When looking at the identified risk factors of age (50 years or older), ulceration, Breslow thickness greater than 3.5 mm, nonaxillary basin, and tumor burden of maximum diameter of 1 mm or greater and/or metastasis area of 5% or greater and excluding missing value cases, basin disease-free rates at 5 years were 96% (95% CI, 88-100) for patients with 0 risk factors, 89% (95% CI, 82-96) for 1 risk factor, 86% (95% CI, 80-93) for 2 risk factors, 80% (95% CI, 71-89) for 3 risk factors, 61% (95% CI, 48-74) for 4 risk factors, and 54% (95% CI, 36-72) for 5 or 6 risk factors. This randomized clinical trial was the largest prospective evaluation of long-term regional basin control in patients with melanoma who had nodal observation after removal of a positive SLN. SLN biopsy without CLND cleared disease in the affected nodal basin in most patients, even those with multiple risk factors for in-basin recurrence. In addition to its well-validated value in staging, SLN biopsy may also be regarded as therapeutic in some patients. ClinicalTrials.gov Identifier: NCT00297895