Frontiers of finance: Evolution and efficient markets

In this review article we explore several recent advances in the quantitative modeling of financial markets. We begin with the Efficient Markets Hypothesis and describe how this controversial idea has stimulated a number of new directions of research, some focusing on more elaborate mathematical models that are captable of rationalizing the empirical facrts, others taking a completely different different tack in rejecting rationality altogether. One of the most promising directions is to view financial markets from a biological perspective and, specifically, with an evolutionary framework in which markets, instruments, institutions, and investors interact and evolve dynamically according to the "law" of economic selection. Under this view, financial agents compete and adapt, but they do not necessarily do so in an optimal fashion. Evolutionary and ecological models of financial markets is truly a new frontier whose exploration has just begun.Comment: 2 page

Shooting the Auctioneer

Most dynamic stochastic general equilibrium models of the macroeconomy assume that labor is traded in a spot market. Two exceptions by David Andolfatto and Monika Merz combine a two-sided search model with a one-sector real business cycle model. These hybrid models are successful, in some dimensions, but they cannot account for observed volatility in unemployment and vacancies. Following suggestions by Robert Hall and Robert Shimer, this paper shows that a relatively standard DSGE model with sticky wages can account for these facts. Using a second-order approximation to the policy function we simulate moments of an artificial economy with and without sticky wages and we document the dependence of unemployment and vacancy volatility on two key parameters; the disutility of effort and the degree of wage stickiness. We compute the welfare costs of the sticky wage equilibrium and find them to be small.

HERMIT: Mechanized Reasoning during Compilation in the Glasgow Haskell Compiler

It is difficult to write programs which are both correct and fast. A promising approach, functional programming, is based on the idea of using pure, mathematical functions to construct programs. With effort, it is possible to establish a connection between a specification written in a functional language, which has been proven correct, and a fast implementation, via program transformation. When practiced in the functional programming community, this style of reasoning is still typically performed by hand, by either modifying the source code or using pen-and-paper. Unfortunately, performing such semi-formal reasoning by directly modifying the source code often obfuscates the program, and pen-and-paper reasoning becomes outdated as the program changes over time. Even so, this semi-formal reasoning prevails because formal reasoning is time-consuming, and requires considerable expertise. Formal reasoning tools often only work for a subset of the target language, or require programs to be implemented in a custom language for reasoning. This dissertation investigates a solution, called HERMIT, which mechanizes reasoning during compilation. HERMIT can be used to prove properties about programs written in the Haskell functional programming language, or transform them to improve their performance. Reasoning in HERMIT proceeds in a style familiar to practitioners of pen-and-paper reasoning, and mechanization allows these techniques to be applied to real-world programs with greater confidence. HERMIT can also re-check recorded reasoning steps on subsequent compilations, enforcing a connection with the program as the program is developed. HERMIT is the first system capable of directly reasoning about the full Haskell language. The design and implementation of HERMIT, motivated both by typical reasoning tasks and HERMIT's place in the Haskell ecosystem, is presented in detail. Three case studies investigate HERMIT's capability to reason in practice. These case studies demonstrate that semi-formal reasoning with HERMIT lowers the barrier to writing programs which are both correct and fast

Use of routinely collected data in a UK cohort of publicly funded randomised clinical trials [version 2]

Routinely collected data about health in medical records, registries and hospital activity statistics is now routinely collected in an electronic form. The extent to which such sources of data are now being routinely accessed to deliver efficient clinical trials, is unclear. The aim of this study was to ascertain current practice amongst a United Kingdom (UK) cohort of recently funded and ongoing randomised controlled trials (RCTs) in relation to sources and use of routinely collected outcome data. Recently funded and ongoing RCTs were identified for inclusion by searching the National Institute for Health Research journals library. Trials that have a protocol available were assessed for inclusion and those that use or plan to use routinely collected health data (RCHD) for at least one outcome were included. RCHD sources and outcome information were extracted. Of 216 RCTs, 102 (47%) planned to use RCHD. A RCHD source was the sole source of outcome data for at least one outcome in 46 (45%) of those 102 trials. The most frequent sources are Hospital Episode Statistics (HES) and Office for National Statistics (ONS), with the most common outcome data to be extracted being on mortality, hospital admission, and health service resource use. Our study has found that around half of publicly funded trials in a UK cohort (NIHR HTA funded trials that had a protocol available) plan to collect outcome data from routinely collected data sources. This is much higher than the figure of 8% found in a cohort of 189 RCTs published since 2000, the majority of which were carried out in North America (McCord et al ., 2019)

Reducing weight and BMI following gestational diabetes: A systematic review and meta-analysis of digital and telemedicine interventions

Women with past gestational diabetes mellitus (GDM) are at risk of subsequent type 2 diabetes and adverse cardiovascular events. Digital and telemedicine interventions targeting weight loss and reductions in body mass index (BMI) may help reduce risk for women with GDM. The aim was to compare the effectiveness of digital or telemedicine intervention with usual care. Randomized controlled trials (RCTs) were identified in Embase, Medline, CINAHL, PsycINFO and the Cochrane Library. Included trials recruited women with prior GDM but without pre-existing diabetes, and tested a digital or telemedicine intervention with or without an in-person component. Data extraction was carried out independently by two authors. The search yielded 898 citations. Eighteen articles reporting 15 trials were included, of which 8 tested digital interventions. Reported outcomes included weight, BMI, fasting plasma glucose and waist circumference. None of the included trials reported type 2 diabetes incidence or cardiovascular risk. Data were pooled using a random-effects model. The point estimate favored the intervention but was non-significant for both BMI (−0.90 kg/m2, 95% CI −1.89 to 0.09; p=0.08) and weight (−1.83 kg, 95% CI −4.08 to 0.42, p=0.11). Trials evaluating digital and telemedicine interventions identified clinically relevant, but non-significant improvements in BMI and weight compared with control. No trials assessed type 2 diabetes occurrence as an outcome. More well-designed RCTs with adequate power and long-term follow-up are needed to identify the impact of these interventions on type 2 diabetes occurrence

High-throughput chromatin accessibility profiling at single-cell resolution.

Here we develop a high-throughput single-cell ATAC-seq (assay for transposition of accessible chromatin) method to measure physical access to DNA in whole cells. Our approach integrates fluorescence imaging and addressable reagent deposition across a massively parallel (5184) nano-well array, yielding a nearly 20-fold improvement in throughput (up to ~1800 cells/chip, 4-5 h on-chip processing time) and library preparation cost (~81¢ per cell) compared to prior microfluidic implementations. We apply this method to measure regulatory variation in peripheral blood mononuclear cells (PBMCs) and show robust, de novo clustering of single cells by hematopoietic cell type

Lobelia dortmanna - light, growth strategy and zonation

This thesis seeks to distinguish the main environmental parameters controlling the growth of Lobelia dortmanna and, by consideration of field conditions, describe which of these controls is most important in determining the zonation of the species, both horizontal and vertical, in Scottish lochs. A detailed analysis of growth across one season was undertaken in a Sutherland lochan, studying populations on sites of different nutrient status. Continuous recordings of temperature and light and monthly measurements of photosynthesis, soluble carbohydrate content and leaf production show continuous growth across the year. However, major increases in growth are strongly correlated to light increases, and only weakly with temperature. No differences occur between sites, so nutrient limitation is not thought to be important in growth. Germination studies reveal that seeds are absolute requirers of light for germination, are red-light promoted and require a cold stratification period before germination. Seeds germinate in low light, under conditions that seedlings subsequently cannot survive in. Examination of the light regime in Scottish lochs reveals that there is sufficient light for germination below the depth limit of zonation. Thus zonation is not controlled by a light requirement for germination. Studies of photosynthesis, pigment and carboxylase variations with depth in L. dortmanna reveal some ability to respond to shading, particularly increasing chlorophyll levels. However, chlorophyll/ carboxylase ratios do not change, so indicating the plant is not typical of shade-adapting species. It is concluded that light control of photosynthetic production is the most important factor in controlling growth and zonation

The DiGEM trial protocol--a randomised controlled trial to determine the effect on glycaemic control of different strategies of blood glucose self-monitoring in people with type 2 diabetes [ISRCTN47464659].

BACKGROUND: We do not yet know how to use blood glucose self-monitoring (BGSM) most effectively in the self-management of type 2 diabetes treated with oral medication. Training in monitoring may be most effective in improving glycaemic control and well being when results are linked to behavioural change. METHODS/DESIGN: DiGEM is a three arm randomised parallel group trial set in UK general practices. A total of 450 patients with type 2 diabetes managed with lifestyle or oral glucose lowering medication are included. The trial compares effectiveness of three strategies for monitoring glycaemic control over 12 months (1) a control group with three monthly HbA1c measurements; interpreted with nurse-practitioner; (2) A self-testing of blood glucose group; interpreted with nurse- practitioner to inform adjustment of medication in addition to 1; (3) A self-monitoring of blood glucose group with personal use of results to interpret results in relation to lifestyle changes in addition to 1 and 2. The trial has an 80% power at a 5% level of significance to detect a difference in change in the primary outcome, HbA1c of 0.5% between groups, allowing for an attrition rate of 10%. Secondary outcome measures include health service costs, well-being, and the intervention effect in sub-groups defined by duration of diabetes, current management, health status at baseline and co-morbidity. A mediation analysis will explore the extent to which changes in beliefs about self-management of diabetes between experimental groups leads to changes in outcomes in accordance with the Common Sense Model of illness. The study is open and has recruited more than half the target sample. The trial is expected to report in 2007. DISCUSSION: The DiGEM intervention and trial design address weaknesses of previous research by use of a sample size with power to detect a clinically significant change in HbA1c, recruitment from a well-characterised primary care population, definition of feasible monitoring and behaviour change strategies based on psychological theory and evidence, and measures along the hypothesised causal path from cognitions to behaviours and disease and well being related outcomes. The trial will provide evidence to support, focus or discourage use of specific BGSM strategies.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Biophysical and structural studies of chlorophyll biosynthetic enzymes magnesium chelatase and protochlorophyllide reductase

Photosynthetic organisms must generate chlorophyll, the light capturing molecule integral for photosynthesis, whilst also regulating production to adapt to environmental conditions. Chlorophyll is so fundamental for photosynthesis that it is important to understand its biosynthetic pathway; consequently, this sequence of reactions has been studied extensively for several decades, culminating in the engineering of the heterotroph E. coli to produce chlorophyll. Two key regulatory points in the pathway are i) at the branchpoint between haem and chlorophyll biosynthesis, where a magnesium ion is inserted into the porphyrin ring, catalysed by the multi-subunit enzyme magnesium chelatase (MgCH); and ii) the light-dependent reduction of the C17-C18 double bond, catalysed by protochlorophyllide oxidoreductase (POR). Despite the extensive work performed to biochemically describe these enzymes, the full reaction mechanisms are still unknown, and the limited amount of structural information for either enzyme has hindered complete characterisation. The work reported in this thesis has used a range of biochemical, biophysical and structural techniques to study these biologically important and mechanistically unique enzymes: microscale thermophoresis, kinetic analysis and cross-linking mass spectrometry revealed that the driving force behind chelation, the ATPase activity of the AAA+ ChlI subunit, is linked to the chelating ChlH protein via the regulatory ChlD subunit; X-ray crystallography-guided mutagenesis determined the porphyrin binding site in ChlH; (cryo)-electron microscopy was used to initiate structural investigations into the quaternary organisation of MgCH and POR; and 2-dimensional electronic spectroscopy was applied to the light-initiated reaction catalysed by POR, the first use of this complex technique on an enzyme, potentially revealing a novel intermediate in the reaction that is formed on the femtosecond time-scale. The work presented in this thesis aims to develop our biochemical understanding of MgCH and POR, and lay the foundations for further structural and mechanistic studies of these interesting enzymes of chlorophyll biosynthesis