Inferential stability in systems biology

The modern biological sciences are fraught with statistical difficulties. Biomolecular stochasticity, experimental noise, and the “large p, small n” problem all contribute to the challenge of data analysis. Nevertheless, we routinely seek to draw robust, meaningful conclusions from observations. In this thesis, we explore methods for assessing the effects of data variability upon downstream inference, in an attempt to quantify and promote the stability of the inferences we make. We start with a review of existing methods for addressing this problem, focusing upon the bootstrap and similar methods. The key requirement for all such approaches is a statistical model that approximates the data generating process. We move on to consider biomarker discovery problems. We present a novel algorithm for proposing putative biomarkers on the strength of both their predictive ability and the stability with which they are selected. In a simulation study, we find our approach to perform favourably in comparison to strategies that select on the basis of predictive performance alone. We then consider the real problem of identifying protein peak biomarkers for HAM/TSP, an inflammatory condition of the central nervous system caused by HTLV-1 infection. We apply our algorithm to a set of SELDI mass spectral data, and identify a number of putative biomarkers. Additional experimental work, together with known results from the literature, provides corroborating evidence for the validity of these putative biomarkers. Having focused on static observations, we then make the natural progression to time course data sets. We propose a (Bayesian) bootstrap approach for such data, and then apply our method in the context of gene network inference and the estimation of parameters in ordinary differential equation models. We find that the inferred gene networks are relatively unstable, and demonstrate the importance of finding distributions of ODE parameter estimates, rather than single point estimates

Corporate Speech in Citizens United vs. Federal Election Commission

In its January 20th, 2010 decision in Citizens United vs. Federal Election Commission, the United States Supreme Court ruled that certain restrictions on independent expenditures by corporations for political advocacy violate the First Amendment of the Constitution, which provides that “Congress shall make no law […] abridging the freedom of speech, or of the press; or the right of the people peaceably to assemble, and to petition the Government for a redress of grievances.” Justice Kennedy, writing for the 5-4 majority, held that “[b]y suppressing the speech of manifold corporations, both for-profit and non-profit, the Government prevents their voices and view-points from reaching the public and advising voters on which person or entities are hostile to their interests” (Citizens United vs. Federal Election Commission 558 U.S. 38-9 (2010); emphasis added). Much of the language of the opinion, and some of its reasoning, as this passage illustrates, presupposes that corporations are agents capable of speech, and that it is (at least in part) in the light of this that limitations on political advocacy by corporations are prohibited by the Constitution. While there are other strands in the argument, they are interwoven with the conception of the corporation as agent and speaker, with its voice and its viewpoints. The dissenters on the court objected on precisely this point (among others). Justice Stevens wrote sarcastically in his dissent, joined by Justices Ginsburg, Breyer, and Sotomayor, that “[u]nder the majority’s view, I suppose it may be a First Amendment problem that corporations are not permitted to vote, given that voting is, among other things, a form of speech” (558 U.S. 33 (2010)). Justice Sotomayor suggested in oral argument that the Court’s century-old practice of treating corporations as persons rests on a conceptual mistake. My concern in this essay is not with the question whether the restrictions violate the Constitution. There are many issues that bear on this which will be outside the scope of my discussion. My concern is with the proper conceptual framework for understanding the agency of corporations and corporate speech, and the role that conceptions of these play in the background of the majority’s reasoning. The issue is legal, but it also has philosophical, conceptual and semantic aspects. It will be the latter aspects, and their potential to shed light on legal reasoning, that are my main focus. An adequate framework requires saying what properly speaking the corporation is, how agency is expressed through the corporation, whose agency it is, centrally whether the corporation is an agent or person in its own right, and in what sense it can be said to be capable of speech. I draw on recent work in collective action theory, particularly with respect to the semantics of collective action sentences (Ludwig 2007) and the analysis of the proxy agency in collective action (Ludwig 2014), to show (i) that corporations are neither genuine agents nor (therefore) capable of engaging in genuine speech, (ii) that consequently the First Amendment does not apply to corporations per se, and (iii) that a better understanding of the mechanisms of corporate agency casts doubt on more indirect arguments for extending the First Amendment to “corporate speech” as well

The future for primary physical education

An in-depth examination of secondary research was undertaken together with a focussed case study to investigate whether current practices within primary physical education (PE) were best serving the learning needs of children in primary schools. A secondary purpose of this research was to examine the implications for this area of primary education regarding the professionalisation of sports coaching. The study was conducted within a unitary authority in the South West of England. Semi-structured interviews were conducted, firstly with both Partnership Development Managers (PDMs), followed up by questionnaires carried out with all of their School Sport Co-ordinators (SSCo's). Subsequent semi-structured interviews were then conducted with a primary school head teacher, a head of primary Initial Teacher Education (ITE), and with the only specialist primary PE teacher found within this authority. These research processes extrapolated information which highlighted current practices in many primary schools with regards to their PE delivery, and the findings illustrated that whilst current PE provision in most secondary schools was generally believed to be of a high standard, embracing recent initiatives and the current National Curriculum, the delivery of PE in primary schools was found to be less consistent. After several processes of inductive research it was concluded that widespread changes in the whole primary PE provision, starting from Initial Teacher Education, ought to be considered