Online Learning and Profit Maximization from Revealed Preferences

We consider the problem of learning from revealed preferences in an online setting. In our framework, each period a consumer buys an optimal bundle of goods from a merchant according to her (linear) utility function and current prices, subject to a budget constraint. The merchant observes only the purchased goods, and seeks to adapt prices to optimize his profits. We give an efficient algorithm for the merchant's problem that consists of a learning phase in which the consumer's utility function is (perhaps partially) inferred, followed by a price optimization step. We also consider an alternative online learning algorithm for the setting where prices are set exogenously, but the merchant would still like to predict the bundle that will be bought by the consumer for purposes of inventory or supply chain management. In contrast with most prior work on the revealed preferences problem, we demonstrate that by making stronger assumptions on the form of utility functions, efficient algorithms for both learning and profit maximization are possible, even in adaptive, online settings

Anaesthesia for emergency and elective hip surgery: improving patient outcomes.

This thesis is presented in two parts. The first is concerned with the management of patients undergoing repair of hip fracture while the second part describes a randomised controlled trial examining analgesic options after total hip replacement. Musculoskeletal disease has the fourth greatest impact on the health of the world’s population (when both death and disability are considered) and is the second most common cause of disability globally. Disability due to musculoskeletal disease has risen by 45% over the last 20 years compared to the 33% average increase seen across other disease groups. This is likely to increase unless action is taken to resolve some of the problems. This has been recognised by The European Parliament Leading Committee on the Horizon 2020 Programme (the European Union Research Framework Programme) resulting in the identification of rheumatic and musculoskeletal conditions as a priority for research over the next 7 years. Glasgow Royal Infirmary is a tertiary referral centre for orthopaedic and trauma surgery undertaking a high volume of both elective and emergency procedures each year. I wished to investigate current standards of care relating to patients undergoing emergency surgery and to establish whether by benchmarking our practice against national data, we could identify areas for improvement. Hip fracture repair was chosen for analysis as it is a common, serious and costly condition that occurs in an increasingly elderly, frail and dependent patient population. Hip fracture is a worldwide concern and a significant public health challenge. Important patient outcomes such as time to theatre, 30 day mortality and length of stay were analysed and compared against national audit data. These data compared favourably. Prior to commencing this work, staff members were asked to communicate any opportunities they saw for care to be improved. Certain sub-populations were identified by staff as meriting particular attention. These were patients admitted to ICU and patients taking warfarin. The sub-population of patients who were taking warfarin and required admission for repair of hip fracture were particularly frail and resulted in a number of management challenges for staff. A quality improvement endeavour was employed in order to standardise management, reduce confusion, expedite time to theatre and ensure adequate thromboprophylaxis throughout the peri-operative period. This work resulted in the production of a protocol to guide management and is subject to ongoing review and audit. The role of anaesthesia in the performance of elective total hip replacement surgery was also investigated. Total hip replacement is one of the most commonly performed surgical procedures in the United Kingdom, can result in improved quality of life, and is considered to be cost effective. In Glasgow Royal Infirmary, anaesthesia is most commonly performed using spinal anaesthetic with the addition of an opioid. Spinal opioids, whilst effective, are associated with side-effects of which the most serious is respiratory depression. Other adverse effects such as pruritus and nausea and vomiting may delay recovery and impact upon a patient’s satisfaction with their experience. I carried out a randomised controlled, double blinded trial to assess whether a regional anaesthetic technique (ultrasound guided fascia iliaca block) could be used as an alternative to spinal morphine. This technique has not yet been assessed clinically in the published literature, though it has shown promise as being more reliable when compared to the landmark based technique. A non-inferiority design was employed in order to compare these two techniques. The primary outcome was 24 hour intravenous morphine consumption. After obtaining the necessary approvals from the West of Scotland Research and Ethics Committee and the West of Scotland Research and Development Department, recruitment was commenced in May 2011. Peer review was received from a journal of trial methodology and the protocol was published. Further peer review and funding was received from the European Society for Anaesthesia and Pain Therapy as well as a local peri-operative research fund. This study shows that ultrasound guided fascia iliaca block is not non-inferior to spinal morphine, or in other words, that ultrasound guided fascia iliaca block is unacceptably worse than spinal morphine in the provision of analgesia after hip replacement. Adverse effects were not statistically significantly different between groups and reassuringly, there were no episodes of respiratory depression or sedation in either group. This study has clear implications for practice and would suggest that spinal morphine remains an effective anaesthetic and analgesic agent in this patient group

Routine prophylactic esketamine for the prevention of maternal pain during cesarean delivery

No abstract available

In vitro and Computational Modelling of Drug Delivery across the Outer Blood-Retinal Barrier

The ability to produce rapid, cost-effective and human-relevant data has the potential to accelerate development of new drug delivery systems. Intraocular drug delivery is an area undergoing rapid expansion due to the increase in sight-threatening diseases linked to increasing age and lifestyle factors. The outer bloodretinal barrier (OBRB) is important in this area of drug delivery, as it separates the eye from the systemic blood flow. This study reports the development of complementary in vitro and in silico models to study drug transport from silicone oil across the outer blood-retinal barrier. Monolayer cultures of a human retinal pigmented epithelium cell line, ARPE-19, were added to chambers and exposed to a controlled flow to simulate drug clearance across the OBRB. Movement of dextran molecules and release of ibuprofen from silicone oil in this model were measured. Corresponding simulations were developed using COMSOL Multiphysics computational fluid dynamics (CFD) software and validated using independent in vitro data sets. Computational simulations were able to predict dextran movement and ibuprofen release, with all of the features of the experimental release profiles being observed in the simulated data. Simulated values for peak concentrations of permeated dextran and ibuprofen released from silicone oil were within 18% of the in vitro results. This model could be used as a predictive tool of drug transport across this important tissue

Long-term functional patency and cost-effectiveness of arteriovenous fistula creation under regional anesthesia: a randomized controlled trial

BACKGROUND:Regional anesthesia improves short-term blood flow through arteriovenous fistulas (AVFs). We previously demonstrated that, compared with local anesthesia, regional anesthesia improves primary AVF patency at 3 months. METHODS:To study the effects of regional versus local anesthesia on longer-term AVF patency, we performed an observer-blinded randomized controlled trial at three university hospitals in Glasgow, United Kingdom. We randomly assigned 126 patients undergoing primary radiocephalic or brachiocephalic AVF creation to receive regional anesthesia (brachial plexus block; 0.5% L-bupivacaine and 1.5% lidocaine with epinephrine) or local anesthesia (0.5% L-bupivacaine and 1% lidocaine). This report includes findings on primary, functional, and secondary patency at 12 months; reinterventions; and additional access procedures (primary outcome measures were previously reported). We analyzed data by intention to treat, and also performed cost-effectiveness analyses. RESULTS:At 12 months, we found higher primary patency among patients receiving regional versus local anesthesia (50 of 63 [79%] versus 37 of 63 [59%] patients; odds ratio [OR], 2.7; 95% confidence interval [95% CI], 1.6 to 3.8; P=0.02) as well as higher functional patency (43 of 63 [68%] versus 31 of 63 [49%] patients; OR, 2.1; 95% CI, 1.5 to 2.7; P=0.008). In 12 months, 21 revisional procedures, 53 new AVFs, and 50 temporary dialysis catheters were required. Regional anesthesia resulted in net savings of £195.10 (US$237.36) per patient at 1 year, and an incremental cost-effectiveness ratio of approximately £12,900 (US$15,694.20) per quality-adjusted life years over a 5-year time horizon. Results were robust after extensive sensitivity and scenario analyses. CONCLUSIONS:Compared with local anesthesia, regional anesthesia significantly improved both primary and functional AVF patency at 1 year and is cost-effective. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER:Local Anaesthesia versus Regional Block for Arteriovenous Fistulae, NCT01706354

The relationship between anaesthetic technique, clinicopathological characteristics and the magnitude of the postoperative systemic inflammatory response in patients undergoing elective surgery for colon cancer

Background/aim: The magnitude of the postoperative systemic inflammatory response (SIR) is now recognised to be associated with both short and long-term outcomes in patients undergoing surgery for colon cancer. During such surgery, it is unclear whether the anaesthetic regimens influence the magnitude of the postoperative SIR, independent of other factors. The aim of the present study was to examine the association between anaesthetic agents, clinicopathological characteristics and the magnitude of the postoperative SIR in patients undergoing elective surgery for colon cancer. Methods: Patients with colon cancer who underwent elective open or laparoscopic surgery between 2008 and 2016 (n = 409) were studied at a single center. The relationship between type of anaesthesia, surgical technique; open (n = 241) versus laparoscopic (n = 168) and clinicopathological characteristics was examined by using chi-square testing. The chi-square test was used to determine which anaesthetic group influences the POD 2 CRP for only patients undergoing elective open colon surgery. Results: The majority of patients were <75 years old, male, normal weight or obese, underwent open surgery and had regional anaesthesia, in particular an epidural approach. There was a significant association between type of anaesthesia and post-operative CRP on day 2 (p <0.001) in patients undergoing open surgery but not laparoscopic surgery. Other factors associated with type of anaesthesia included; year of operation (p <0.01), surgical technique (p <0.001), and preoperative dexamethasone (p <0.01). Conclusion: In patients undergoing surgery for elective colon cancer, the type of anaesthesia varied over time. The type of anaesthesia appears to influence the magnitude of the postoperative SIR on post-operative day 2 in open surgery but not laparoscopic surgery. Future work using prospective study design is required to better define this relationship

Nutrient enrichment induces dormancy and decreases diversity of active bacteria in salt marsh sediments

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Nature Communications 7 (2016): 12881, doi:10.1038/ncomms12881.Microorganisms control key biogeochemical pathways, thus changes in microbial diversity, community structure and activity can affect ecosystem response to environmental drivers. Understanding factors that control the proportion of active microbes in the environment and how they vary when perturbed is critical to anticipating ecosystem response to global change. Increasing supplies of anthropogenic nitrogen to ecosystems globally makes it imperative that we understand how nutrient supply alters active microbial communities. Here we show that nitrogen additions to salt marshes cause a shift in the active microbial community despite no change in the total community. The active community shift causes the proportion of dormant microbial taxa to double, from 45 to 90%, and induces diversity loss in the active portion of the community. Our results suggest that perturbations to salt marshes can drastically alter active microbial communities, however these communities may remain resilient by protecting total diversity through increased dormancy

Attitudes towards the use of perioperative steroids in resectional colorectal cancer surgery in the UK: a qualitative study

Introduction: Resectional surgery remains the mainstay of treatment for colorectal cancer. A heightened postoperative systemic inflammatory response has been shown to correlate negatively with short/long-term outcomes. Perioperative steroid administration may help to alleviate this systemic inflammatory response. This survey has been carried out to assess current attitudes towards perioperative steroid use and to gauge interest in a randomised control trial in this area. Method: An internet-based survey consisting of 9 questions was circulated via email. Those responses from outside the United Kingdom were excluded. Result: 74 doctors from the United Kingdom, predominantly Consultant Anaesthetists (54%) responded to this survey. 77% gave some or all of their patients steroids, in 75% of cases at the discretion of the anaesthetist. The main perceived benefit was to reduce postoperative nausea and vomiting. Diabetics and those deemed at high risk of wound infection were the group in whom most respondents would be reluctant to give steroids. 32% of respondents had no concerns. 87% of respondents felt that that a randomised trial in this field would be of clinical interest with most respondents (58%) preferring a three-armed trial – no steroids vs low dose steroids vs high dose steroids. Conclusion: – This survey indicated that perioperative steroid use is currently widespread. Sufficient equipoise exists for a trial in this area with regard to examining the impact of dexamethasone on postoperative complications and the postoperative systemic inflammatory response. Respondents favoured a 3-armed trial – no steroids vs low-dose steroids vs high-dose steroids

Replacement of the Trabecular Meshwork Cells—A Way Ahead in IOP Control?

Glaucoma is one of the leading causes of vision loss worldwide, characterised with irreversible optic nerve damage and progressive vision loss. Primary open-angle glaucoma (POAG) is a subset of glaucoma, characterised by normal anterior chamber angle and raised intraocular pressure (IOP). Reducing IOP is the main modifiable factor in the treatment of POAG, and the trabecular meshwork (TM) is the primary site of aqueous humour outflow (AH) and the resistance to outflow. The structure and the composition of the TM are key to its function in regulating AH outflow. Dysfunction and loss of the TM cells found in the natural ageing process and more so in POAG can cause abnormal extracellular matrix (ECM) accumulation, increased TM stiffness, and increased IOP. Therefore, repair or regeneration of TM’s structure and function is considered as a potential treatment for POAG. Cell transplantation is an attractive option to repopulate the TM cells in POAG, but to develop a cell replacement approach, various challenges are still to be addressed. The choice of cell replacement covers autologous or allogenic approaches, which led to investigations into TM progenitor cells, induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs) as potential stem cell source candidates. However, the potential plasticity and the lack of definitive cell markers for the progenitor and the TM cell population compound the biological challenge. Morphological and differential gene expression of TM cells located within different regions of the TM may give rise to different cell replacement or regenerative approaches. As such, this review describes the different approaches taken to date investigating different cell sources and their differing cell isolation and differentiation methodologies. In addition, we highlighted how these approaches were evaluated in different animal and ex vivo model systems and the potential of these methods in future POAG treatment