Winning Ideas: Lessons from Free-market Economics

For economic ideas to take root and change history, a number of ingredients need to be present, ranging from individual agents to policy implementation. This paper identifies certain strategic levers that underlay the success of free market economists in promoting their approach in academia, society, and government. How did these economists move from a marginalized position where they could not publish or receive tenure and where their students were not hired at other leading universities, to a position of dominance? In particular, it examines the impact of F.A. Hayek, and of such institutions as the Mont Pelerin Society, the Institute for Economic Affairs (IEA) in Britain, and the funding arrangements. The paper draws on the wealth of secondary literature regarding the spread of free market economic ideas, particularly in the US, Latin America, and the UK, to identify five strategic activities and methods of transmission that were central to their advance, and will be relevant to others.

Functional Nanocomposite Surfaces for Antibacterial, Oil–Water Separation, and Optical Applications

Surface functionalisation can be used to modify the interaction between liquids and solid surfaces which is of importance in many applications such as self-cleaning, anti-fouling, and anti-fogging. The use of nanocomposite materials also provides a way of improving particular properties of the film even when small amounts of nano-material is used. The use of nanocomposite coatings to tailor the wettability, as well as to incorporate additional properties into surface coatings has been studied in this thesis for antibacterial, oil–water separation, and optical applications. Chapter 1 provides an introduction to nanocomposite coatings including a brief review of how they are prepared and for what applications they are used. Chapter 2 provides information on how surface wettability is measured as well as summarising the other experimental techniques used throughout this thesis. Chapter 3 describes the application of polymer–nanoparticle–fluorosurfactant complex nanocomposite coatings for antibacterial oil–water separation applications. Porous substrates coated with these polymer–nanoparticle–fluorosurfactant complex nanocomposite coatings are found to readily separate oil–water mixtures under both static and continuous flow as well as displaying antibacterial surface properties against Escherichia coli (Gram-negative bacteria) and Staphylococcus aureus (Gram-positive bacteria). A key advantage of this approach for coating substrates is its single-step simplicity. Potential applications include provision of safe drinking water, environmental pollution clean-up, and anti-fogging. Chapter 4 utilises a single-step, low temperature, solventless atomised spray plasma deposition technique for the preparation of antibacterial polymer–metallosurfactant nanocomposite coatings which are highly active against both Escherichia coli (Gram-negative bacteria) and Staphylococcus aureus (Gram-positive bacteria). Chapter 5 extends the use of the atomised spray plasma deposition technique into optical applications with the preparation of high refractive index hybrid polymer and polymer–inorganic nanocomposite coatings. Refractive indices as high as 1.936 at 635 nm wavelength have been obtained for 4-bromostyrene / toluene + TiO2 layers using very low titania loadings (8% w/v). Thin films with any desired refractive index up to 1.936 can be easily deposited by varying the precursor mixture composition

Benchmarking Deep Learning Architectures for Predicting Readmission to the ICU and Describing Patients-at-Risk

Objective: To compare different deep learning architectures for predicting the risk of readmission within 30 days of discharge from the intensive care unit (ICU). The interpretability of attention-based models is leveraged to describe patients-at-risk. Methods: Several deep learning architectures making use of attention mechanisms, recurrent layers, neural ordinary differential equations (ODEs), and medical concept embeddings with time-aware attention were trained using publicly available electronic medical record data (MIMIC-III) associated with 45,298 ICU stays for 33,150 patients. Bayesian inference was used to compute the posterior over weights of an attention-based model. Odds ratios associated with an increased risk of readmission were computed for static variables. Diagnoses, procedures, medications, and vital signs were ranked according to the associated risk of readmission. Results: A recurrent neural network, with time dynamics of code embeddings computed by neural ODEs, achieved the highest average precision of 0.331 (AUROC: 0.739, F1-Score: 0.372). Predictive accuracy was comparable across neural network architectures. Groups of patients at risk included those suffering from infectious complications, with chronic or progressive conditions, and for whom standard medical care was not suitable. Conclusions: Attention-based networks may be preferable to recurrent networks if an interpretable model is required, at only marginal cost in predictive accuracy

Hepatic acute-phase proteins control innate immune responses during infection by promoting myeloid-derived suppressor cell function

Acute-phase proteins (APPs) are an evolutionarily conserved family of proteins produced mainly in the liver in response to infection and inflammation. Despite vast pro- and antiinflammatory properties ascribed to individual APPs, their collective function during infections remains poorly defined. Using a mouse model of polymicrobial sepsis, we show that abrogation of APP production by hepatocyte-specific gp130 deletion, the signaling receptor shared by IL-6 family cytokines, strongly increased mortality despite normal bacterial clearance. Hepatic gp130 signaling through STAT3 was required to control systemic inflammation. Notably, hepatic gp130–STAT3 activation was also essential for mobilization and tissue accumulation of myeloid-derived suppressor cells (MDSCs), a cell population mainly known for antiinflammatory properties in cancer. MDSCs were critical to regulate innate inflammation, and their adoptive transfer efficiently protected gp130-deficient mice from sepsis-associated mortality. The hepatic APPs serum amyloid A and Cxcl1/KC cooperatively promoted MDSC mobilization, accumulation, and survival, and reversed dysregulated inflammation and restored survival of gp130-deficient mice. Thus, gp130-dependent communication between the liver and MDSCs through APPs controls inflammatory responses during infection

The Double Galaxy Cluster Abell 2465 I. Basic Properties: Optical Imaging and Spectroscopy

Optical imaging and spectroscopic observations of the z = 0.245 double galaxy cluster Abell 2465 are described. This object appears to be undergoing a major merger. It is a double X-ray source and is detected in the radio at 1.4 GHz. This paper investigates signatures of the interaction of the two components. Redshifts were measured to determine velocity dispersions and virial radii of each component. The technique of fuzzy clustering was used to assign membership weights to the galaxies in each clump. Using redshifts of 93 cluster members within 1.4 Mpc of the subcluster centres, the virial masses and anisotropy parameters are derived. 37% of the spectroscopically observed galaxies show emission lines and are predominantly star forming in the diagnostic diagram. No strong AGN sources were found. The emission line galaxies tend to lie between the two cluster centres with more near the SW clump. The luminosity functions of the two subclusters differ. The NE component is similar to many rich clusters, while the SW component has more faint galaxies. The NE clump's light profile follows a single NFW profile with c = 10 while the SW is better fit with an extended outer region and a compact inner core, consistent with available X-ray data indicating that the SW clump has a cooling core. The observed differences and properties of the two components of Abell 2465 are interpreted to have been caused by a collision 2-4 Gyr ago, after which they have moved apart and are now near their apocentres, although the start of a merger remains a possibility. The number of emission line galaxies gives weight to the idea that galaxy cluster collisions trigger star formation.Comment: 21 pages, 18 Figures Replaced typos, mostly in references To appear in MNRAS, Accepted 2010 December 16. Received 2010 December 15; in original form 2010 November 0

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Survival results from an adaptive, multiarm, multistage, platform randomised controlled trial

BACKGROUND Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. METHODS Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m(2)) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at ClinicalTrials.gov (NCT00268476) and ControlledTrials.com (ISRCTN78818544). FINDINGS 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60-71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6%) men were previously treated with local therapy, and median prostate-specific antigen was 65 ng/mL (IQR 23-184). Median follow-up was 43 months (IQR 30-60). There were 415 deaths in the control group (347 [84%] prostate cancer). Median overall survival was 71 months (IQR 32 to not reached) for SOC-only, not reached (32 to not reached) for SOC + ZA (HR 0·94, 95% CI 0·79-1·11; p=0·450), 81 months (41 to not reached) for SOC + Doc (0·78, 0·66-0·93; p=0·006), and 76 months (39 to not reached) for SOC + ZA + Doc (0·82, 0·69-0·97; p=0·022). There was no evidence of heterogeneity in treatment effect (for any of the treatments) across prespecified subsets. Grade 3-5 adverse events were reported for 399 (32%) patients receiving SOC, 197 (32%) receiving SOC + ZA, 288 (52%) receiving SOC + Doc, and 269 (52%) receiving SOC + ZA + Doc. INTERPRETATION Zoledronic acid showed no evidence of survival improvement and should not be part of standard of care for this population. Docetaxel chemotherapy, given at the time of long-term hormone therapy initiation, showed evidence of improved survival accompanied by an increase in adverse events. Docetaxel treatment should become part of standard of care for adequately fit men commencing long-term hormone therapy. FUNDING Cancer Research UK, Medical Research Council, Novartis, Sanofi-Aventis, Pfizer, Janssen, Astellas, NIHR Clinical Research Network, Swiss Group for Clinical Cancer Research

Abiraterone acetate plus prednisolone for metastatic patients starting hormone therapy: 5-year follow-up results from the STAMPEDE randomised trial (NCT00268476)

Abiraterone acetate plus prednisolone (AAP) previously demonstrated improved survival in STAMPEDE, a multiarm, multistage platform trial in men starting long-term hormone therapy for prostate cancer. This long-term analysis in metastatic patients was planned for 3 years after the first results. Standard-of-care (SOC) was androgen deprivation therapy. The comparison randomised patients 1:1 to SOC-alone with or without daily abiraterone acetate 1000 mg + prednisolone 5 mg (SOC + AAP), continued until disease progression. The primary outcome measure was overall survival. Metastatic disease risk group was classified retrospectively using baseline CT and bone scans by central radiological review and pathology reports. Analyses used Cox proportional hazards and flexible parametric models, accounting for baseline stratification factors. One thousand and three patients were contemporaneously randomised (November 2011 to January 2014): median age 67 years; 94% newly-diagnosed; metastatic disease risk group: 48% high, 44% low, 8% unassessable; median PSA 97 ng/mL. At 6.1 years median follow-up, 329 SOC-alone deaths (118 low-risk, 178 high-risk) and 244 SOC + AAP deaths (75 low-risk, 145 high-risk) were reported. Adjusted HR = 0.60 (95% CI: 0.50-0.71; P = 0.31 × 10−9) favoured SOC + AAP, with 5-years survival improved from 41% SOC-alone to 60% SOC + AAP. This was similar in low-risk (HR = 0.55; 95% CI: 0.41-0.76) and high-risk (HR = 0.54; 95% CI: 0.43-0.69) patients. Median and current maximum time on SOC + AAP was 2.4 and 8.1 years. Toxicity at 4 years postrandomisation was similar, with 16% patients in each group reporting grade 3 or higher toxicity. A sustained and substantial improvement in overall survival of all metastatic prostate cancer patients was achieved with SOC + abiraterone acetate + prednisolone, irrespective of metastatic disease risk group

Tragicomic presentations of self : starring Phil Silvers as Bilko : the incomplete comic human

When a performer becomes over-associated with a particular, celebrated comic character can this lead to problems, not merely in terms of type-casting, but in creating confusions for the actor’s own perception of self? In instances where a comic creation is perceived to be an extension of the performer’s actual ‘self’, what dissonances in self construct may arise between the comic actor’s created persona and his/her own presentation of self? This article considers the nature of tensions created through the permeation of persona and person which can beset comedians who become closely identified with their particular mediated role. Can, indeed, over-association with their successful ‘signature’ comic role be seen to prove psychologically destabilising for certain performers whose own fragile, sense of identity becomes further compromised by presentation of their own most familiar and definitive, comic creations? Drawing specifically upon the career and comedy of Phil Silvers (aka ‘Sergeant ‘Bilko’), this article attempts to evaluate the forms of crises of identity that can arise between presentations of public and private selves for those performers who become, in effect, ‘public comic property’

Exploring the impact of public health teams on alcohol premises licensing in England and Scotland (ExILEnS): procotol for a mixed methods natural experiment evaluation.

Background: Recent regulatory changes in the system by which premises are licensed to sell alcohol, have given health representatives a formal role in the process in England and Scotland. The degree to which local public health teams engage with this process varies by locality in both nations, which have different licensing regimes. This study aims to critically assess the impact on alcohol-related harms - and mechanisms - of public health stakeholders’ engagement in alcohol premises licensing from 2012 to 2018, comparing local areas with differing types and intensities of engagement, and examining practice in Scotland and England. Methods: The study will recruit 20 local authority areas where public health stakeholders have actively engaged with the alcohol premises licensing system (the 'intervention’) and match them to a group of 20 lower activity areas using genetic matching. Four work packages are included: (1) Structured interviews and documentary analysis will examine the type and level of intervention activity from 2012 to 2018, creating a novel composite measure of the intensity of such activity and will assess the local licensing system and potential confounding activities over the same period. In-depth interviews with public health, licensing, police and others will explore perceived mechanisms of change, acceptability, and impact. (2) Using longitudinal growth models and time series analyses, the study will evaluate the impact of high and low levels of activity on alcohol-related harms using routine data from baseline 2009 to 2018. (3) Intervention costs, estimated National Health Service cost savings and health gains will be evaluated using the Sheffield Alcohol Policy Model to estimate impact on alcohol consumption and health inequalities. (4) The study will engage public health teams to create a new theory of change for public health involvement in the licensing process using our data. We will share findings with local, national and international stakeholders. Discussion: This interdisciplinary study examines, for the first time, whether and how public health stakeholders involvement in alcohol licensing impacts on alcohol harms. Using mixed methods and drawing on complex systems thinking, it will make an important contribution to an expanding literature evaluating interventions not suited to traditional epidemiological research