Numerical study on some rheological problems of fibre suspensions

This thesis deals with numerical investigations on some rheological problems of fibre suspensions: the fibre level simulation of non-dilute fibre suspensions in shear flow; the numerical simulation of complex fibre suspension flows and simulating the particle motion in viscoelastic flows. These are challenging problems in rheology. Two numerical approaches were developed for simulating non-dilute fibre suspensions from the fibre level. The first is based on a model that accounts for full hydrodynamic interactions between fibres, which are approximately calculated as a superposition of the long-range and short-range hydrodynamic interactions. The long-range one is approximated by using slender body theory and includes infinite particle interactions. The short-range one is approximated in terms of the normal lubrication forces between close neighbouring fibres. The second is based on a model that accounts only for short-range interactions, which comprise the lubrication forces and normal contact and friction forces. These two methods were applied to simulate the microstructure evolution and rheological properties of non-dilute fibre suspensions. The Brownian configuration method was combined with the highly stable finite element method to simulate the complex flow of fibre suspensions. The method is stable and robust, and can provide both micro and macro information. It does not require any closure approximations in calculating the fibre stress tensor and is more efficient and variance reduction, compared to CONNFFESSITT, for example. The flow of fibre suspensions past a sphere in a tube and the shear induced fibre migration were successfully simulated using this method The completed double layer boundary element method was extended to viscoelastic flow cases. A point-wise solver was developed to solve the constitutive equation point by point and the fixed least square method was employed to interpolate and differentiate data locally. The method avoids volume meshing and only requires the boundary mesh on particle surfaces and data points in the flow domain. A sphere settling in the Oldroyd-B fluid and a prolate spheroid rotating in shear flow of the Oldroyd-B fluid were simulated. Based on the simulated orbit of a prolate spheroid in shear flow, a constitutive model for the weakly viscoelastic fibre suspensions was proposed and its predictions were compared with some available experimental results. All simulated results are in general agreement with experimental and other numerical results reported in literature. This indicates that these numerical methods are useful tools in rheological research

Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2–3 trial

Background: Peri-operative chemotherapy and surgery is a standard of care for patients with resectable oesophagogastric adenocarcinoma. Bevacizumab, a monoclonal antibody against VEGF, improves the proportion of patients responding to treatment in advanced gastric cancer. We aimed to assess the safety and efficacy of adding bevacizumab to peri-operative chemotherapy in patients with resectable gastric, oesophagogastric junction, or lower oesophageal adenocarcinoma. Methods: In this multicentre, randomised, open-label phase 2–3 trial, we recruited patients aged 18 years and older with histologically proven, resectable oesophagogastric adenocarcinoma from 87 UK hospitals and cancer centres. We randomly assigned patients 1:1 to receive peri-operative epirubicin, cisplatin, and capecitabine chemotherapy or chemotherapy plus bevacizumab, in addition to surgery. Patients in the control group (chemotherapy alone) received three pre-operative and three post-operative cycles of epirubicin, cisplatin, and capecitabine chemotherapy: 50 mg/m2 epirubicin and 60 mg/m2 cisplatin on day 1 and 1250 mg/m2 oral capecitabine on days 1–21. Patients in the investigational group received the same treatment as the control group plus 7·5 mg/kg intravenous bevacizumab on day 1 of every cycle of chemotherapy and for six further doses once every 21 days following chemotherapy, as maintenance treatment. Randomisation was done by means of a telephone call to the Medical Research Council Clinical Trials Unit, where staff used a computer programme that implemented a minimisation algorithm with a random element to establish the allocation for the patient at the point of randomisation. Patients were stratified by chemotherapy centre, site of tumour, and tumour stage. The primary outcome for the phase 3 stage of the trial was overall survival (defined as the time from randomisation until death from any cause), analysed in the intention-to-treat population. Here, we report the primary analysis results of the trial; all patients have completed treatment and the required number of primary outcome events has been reached. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN 46020948, and with ClinicalTrials.gov, number NCT00450203. Findings: Between Oct 31, 2007, and March 25, 2014, 1063 patients were enrolled and randomly assigned to receive chemotherapy alone (n=533) or chemotherapy plus bevacizumab (n=530). At the time of analysis, 508 deaths were recorded (248 in the chemotherapy alone group and 260 in the chemotherapy plus bevacizumab group). 3-year overall survival was 50·3% (95% CI 45·5–54·9) in the chemotherapy alone group and 48·1% (43·2–52·7) in the chemotherapy plus bevacizumab group (hazard ratio [HR] 1·08, 95% CI 0·91–1·29; p=0·36). Apart from neutropenia no other toxic effects were reported at grade 3 or worse severity in more than 10% of patients in either group. Wound healing complications were more prevalent in the bevacizumab group, occurring in 53 (12%) patients in this group compared with 33 (7%) patients in the chemotherapy alone group. In patients who underwent oesophagogastrectomy, post-operative anastomotic leak rates were higher in the chemotherapy plus bevacizumab group (23 [10%] of 233 in the chemotherapy alone group vs 52 [24%] of 220 in the chemotherapy plus bevacizumab group); therefore, recruitment of patients with lower oesophageal or junctional tumours planned for an oesophagogastric resection was stopped towards the end of the trial. Serious adverse events for all patients included anastomotic leaks (30 events in chemotherapy alone group vs 69 in the chemotherapy plus bevacizumab group), and infections with normal neutrophil count (42 events vs 53). Interpretation: The results of this trial do not provide any evidence for the use of bevacizumab in combination with peri-operative epiribicin, cisplatin, and capecitabine chemotherapy for patients with resectable gastric, oesophagogastric junction, or lower oesophageal adenocarcinoma. Bevacizumab might also be associated with impaired wound healing. Funding: Cancer Research UK, MRC Clinical Trials Unit at University College London, and F Hoffmann-La Roche Limited

Materiality, health informatics and the limits of knowledge production

© IFIP International Federation for Information Processing 2014 Contemporary societies increasingly rely on complex and sophisticated information systems for a wide variety of tasks and, ultimately, knowledge about the world in which we live. Those systems are central to the kinds of problems our systems and sub-systems face such as health and medical diagnosis, treatment and care. While health information systems represent a continuously expanding field of knowledge production, we suggest that they carry forward significant limitations, particularly in their claims to represent human beings as living creatures and in their capacity to critically reflect on the social, cultural and political origins of many forms of data ‘representation’. In this paper we take these ideas and explore them in relation to the way we see healthcare information systems currently functioning. We offer some examples from our own experience in healthcare settings to illustrate how unexamined ideas about individuals, groups and social categories of people continue to influence health information systems and practices as well as their resulting knowledge production. We suggest some ideas for better understanding how and why this still happens and look to a future where the reflexivity of healthcare administration, the healthcare professions and the information sciences might better engage with these issues. There is no denying the role of health informatics in contemporary healthcare systems but their capacity to represent people in those datascapes has a long way to go if the categories they use to describe and analyse human beings are to produce meaningful knowledge about the social world and not simply to replicate past ideologies of those same categories

Special Libraries, April 1933

Volume 24, Issue 3https://scholarworks.sjsu.edu/sla_sl_1933/1002/thumbnail.jp

No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). BCAC is funded by Cancer Research UK [C1287/A10118, C1287/A12014] and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 16 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defense (W81XWH-10-1- 0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Project established by the National Cancer Institute and National Human Genome Research Institute.This is the author accepted manuscript. The final version is available from BMJ Group at http://dx.doi.org/10.1136/jmedgenet-2015-103529

'Duck to water' or 'fish out of water'? Diversity in the experience of negotiating the transition to university

Winstone and Hulme present a critical discussion of the notion of transition to university. They argue that the common emphasis on the challenging nature of the transition fails to acknowledge the diversity in students’ experiences; for some students, the liminality and discomfort experienced during this critical period in their educational journey can be a transformational and empowering rite of passage. Rather than homogenising students’ experiences, Winstone and Hulme argue that it is beneficial to explore the transition experience through the lens of students’ expectations and subsequent experiences and to view the transition to university as part of a trajectory of transition experience within a student’s educational journey. The chapter also presents practical suggestions for engaging multiple student voices in understanding and facilitating positive transition experiences

Consumer behaviour and sales forecast accuracy: what’s going on and how should revenue managers respond?

Since the Lehman’s crash in 2008 anecdotal evidence from the Revenue Management Society in the UK suggests that consumer buying behaviour has changed significantly. Consumers are buying different things, at different times and through different channels. As a result forecast accuracy is poor and many companies are turning off the automated forecasting systems and relying on analysts to predict booking behaviour. Historical data alone cannot be used to predict future sales in times of flux such as these and drawing together a wider range of internal and external data would help improve forecast accuracy. The impact on Revenue Managers varies widely. Where sales forecasts are important, adjustments to Revenue Management (RM) System outputs are needed to retain credibility and stop systems ‘panicking’. When customer behaviour is volatile and poorly understood, there may be a need for novel selling mechanisms such as auctions, or online experimentation to probe the market respons