Stumbling Blocks in Empirical Legal Research: Case Study Research

This article examines the main assumptions and theoretical underpinnings of case study method in legal studies. It considers the importance of research design, including the crucial roles of the academic literature review, the research question and the use of rival theories to develop hypotheses and the practice of identifying the observable implications of those hypotheses. It considers the selection of data sources and modes of analysis to allow for valid analytical inferences to be drawn in respect of them. In doing so it considers, in brief, the importance of case study selection and variations such as single or multi case approaches. Finally it provides thoughts about the strengths and weaknesses associated with undertaking socio-legal and comparative legal research via a case study method, addressing frequent stumbling blocks encountered by legal researchers, as well as ways to militate them. It is written with those new to the method in mind

Gender and the legal academy in the UK: a product of proxies and hiring and promotion practices

In this chapter we examine the differential numbers of men and women in each of the seniority levels of the legal academy with reference to qualitative studies on gender and the legal academy in the literature, and our initial analysis of the UK Higher Education Statistical Agency’s systematically collected data derived from all higher education institutions in the United Kingdom. We then apply the human resource management research literature to these data to seek to understand how decision-making in the academy may explain ongoing inequalities. Our research suggests that the continued disparity in male-female promotion trajectories is, at least in part, a function of the way in which talent, merit, or excellence is understood and operationalised in the academy more widely. We posit that the disparity in the numbers of men and women at the higher levels of the legal academy will only be successfully countered once we adopt a more sophisticated approach to analysing what makes an excellent law teacher/researcher/administrator and then develop and promote people on that basis

Correction: Detection of Chlamydia in the peripheral blood cells of normal donors using in vitro culture, immunofluorescence microscopy and flow cytometry techniques

BACKGROUND: Chlamydia trachomatis (Ct) and Chlamydia pneumoniae (Cp) are medically significant infectious agents associated with various chronic human pathologies. Nevertheless, specific roles in disease progression or initiation are incompletely defined. Both pathogens infect established cell lines in vitro and polymerase chain reaction (PCR) has detected Chlamydia DNA in various clinical specimens as well as in normal donor peripheral blood monocytes (PBMC). However, Chlamydia infection of other blood cell types, quantification of Chlamydia infected cells in peripheral blood and transmission of this infection in vitro have not been examined. METHODS: Cp specific titers were assessed for sera from 459 normal human donor blood (NBD) samples. Isolated white blood cells (WBC) were assayed by in vitro culture to evaluate infection transmission of blood cell borne chlamydiae. Smears of fresh blood samples (FB) were dual immunostained for microscopic identification of Chlamydia-infected cell types and aliquots also assessed using Flow Cytometry (FC). RESULTS: ELISA demonstrated that 219 (47.7%) of the NBD samples exhibit elevated anti-Cp antibody titers. Imunofluorescence microscopy of smears demonstrated 113 (24.6%) of samples contained intracellular Chlamydia and monoclonals to specific CD markers showed that in vivo infection of neutrophil and eosinophil/basophil cells as well as monocytes occurs. In vitro culture established WBCs of 114 (24.8%) of the NBD samples harbored infectious chlamydiae, clinically a potentially source of transmission, FC demonstrated both Chlamydia infected and uninfected cells can be readily identified and quantified. CONCLUSION: NBD can harbor infected neutrophils, eosinophil/basophils and monocytes. The chlamydiae are infectious in vitro, and both total, and cell type specific Chlamydia carriage is quantifiable by FC

Reconfiguring experimental archaeology using 3D reconstruction

Experimental archaeology has long yielded valuable insights into the tools and techniques that featured in past peoples’ relationship with the material world around them. We can determine, for example, how many trees would need to be felled to construct a large round-house of the southern British Iron Age (over one hundred), infer the exact angle needed to strike a flint core in order to knap an arrowhead in the manner of a Neolithic hunter-gatherer, or recreate the precise environmental conditions needed to store grain in underground silos over the winter months, with only the technologies and materials available to Romano-Briton villagers (see Coles 1973; Reynolds 1993). However, experimental archaeology has, hitherto, confined itself to rather rigid, empirical and quantitative questions such as those posed in these examples. This is quite understandable, and in line with good scientific practice, which stipulates that any ‘experiment’ must be based on replicable data, and be reproducible. Despite their potential in this area however, it is notable that digital reconstruction technologies have yet to play a significant role in experimental archaeology. Whilst many excellent examples of digital 3D reconstruction of heritage sites exist (for example the Digital Roman Forum project: http://dlib.etc.ucla.edu/projects/Forum) most, if not all, of these are characterized by a drive to establish a photorealistic re-creation of physical features. This paper will discuss possibilities that lie beyond straightforward positivist re-creation of heritage sites, in the experimental reconstruction of intangible heritage. Between 2010 and 2012, the authors led the Motion in Place Platform project (MiPP: http://www.motioninplace.org/), a capital grant under the AHRC's DEDEFI scheme developing motion capture and analysis tools for exploring how people move through spaces. In the course of MiPP, a series of experiments were conducted using motion capture hardware and software at the Silchester Roman town archaeological excavation in Hampshire, and at the Butser Ancient Farm facility, where Romano-British and Iron Age dwellings have been constructed according to the best experimental practice. As well as reconstructing such Roman and early British dwellings in 3D, the authors were able to use motion capture to reconstruct the kind of activities that – according to the material evidence – are likely to have been carried out by the occupants who used them. Bespoke motion capture suits developed for the project were employed, and the traces captured and rendered with a combination of Autodesk and Unity3D software. This sheds new light on how the reconstructed spaces - and, by inference, their ancient counterparts - were most likely to have been used. In particular the exercises allowed the evaluation and visualisation of changes in behaviour which occur as a result of familiarity with an environment and the acquisition of expertise over time; and to assess how interaction between different actors affects how everyday tasks are carried out

Chlamydia pneumoniae-Specific IgE Is Prevalent in Asthma and Is Associated with Disease Severity

Background: Several Chlamydia pneumoniae (Cp) biomarkers have been associated with asthma but Cp-specific IgE (Cp IgE) has not been investigated extensively. Our objective was to investigate Cp IgE in community adult asthma patients. Methods: (1) Prevalence of Cp IgE (measured by immunoblotting) and Cp DNA (by polymerase chain reaction) in peripheral blood, and biomarker associations with asthma severity. (2) Case-control studies of Cp IgE association with asthma using healthy blood donor (study 1) and non-asthmatic clinic patient (study 2) controls. Results: Of 66 asthma subjects (mean age 40.9 years, range 5–75, 59% male, 45% ever-smokers) 33 (50%) were Cp IgE positive and 16 (24%) were Cp DNA positive (P = 0.001 for association of Cp IgE and DNA). Cp IgE was detected in 21% of mild intermittent asthma v 79% of severe persistent asthma (test for trend over severity categories, P = 0.002). Cp IgE detection was significantly (P = 0.001) associated with asthma when compared to healthy blood donor controls but not when compared to clinic controls. Conclusions: Half of this sample of community asthma patients had detectable IgE against C. pneumoniae. Cp IgE was strongly and positively associated with asthma severity and with asthma when healthy blood donor controls were used. These results support the inclusion of Cp IgE as a biomarker in future studies of infectious contributions to asthma pathogenesis

The ability to accumulate deoxyuridine triphosphate and cellular response to thymidylate synthase (TS) inhibition

Thymidylate synthase (TS) is an important enzyme catalysing the reductive methylation of dUMP to dTMP that is further metabolized to dTTP for DNA synthesis. Loss of viability following TS inhibition occurs as a consequence of depleted dTTP pools and at least in some cell lines, accumulation of dUTP and subsequent misincorporation of uracil into DNA. The expansion in dUTP pools is largely determined by the expression of the pyrophosphatase, dUTPase. Our previous work has shown that following TS inhibition the ability to accumulate dUTP was associated with an earlier growth inhibitory effect. 3 human lung tumour cell lines and HT29 human colon tumour cells transfected with dUTPase have been used to investigate the relationship between loss of viability following TS inhibition and dUTP accumulation. Cell cycle arrest typical of TS inhibition was an early event in all cell lines and occurred irrespective of the ability to accumulate dUTP or p53 function. However, a large expansion of dUTP pools was associated with mature DNA damage (4 h) and an earlier loss of viability following TS inhibition compared to cells in which dUTP pools were not expanded. In A549 cells damage to mature DNA may have been exacerbated by significantly higher activity of the excision repair enzyme, uracil-DNA glycosylase. Consistent with results using different inhibitors of TS, transfection of dUTPase into HT29 cells significantly reduced the cytotoxicity of a 24 h but not 48 h exposure to ZD9331. Although loss of viability can be mediated through dTTP deprivation alone, the uracil misincorporation pathway resulted in an earlier commitment to cell death. The relevance of this latter pathway in the clinical response to TS inhibitors deserves further investigation. © 2001 Cancer Research Campaign http://www.bjcancer.co

Deoxyuridine triphosphatase (dUTPase) expression and sensitivity to the thymidylate synthase (TS) inhibitorD9331

Uracil DNA misincorporation and misrepair of DNA have been recognized as important events accompanying thymidylate synthase (TS) inhibition. dUTPase catalyses the hydrolysis of dUTP to dUMP, thereby maintaining low intracellular dUTP. We have addressed the relationship between dUTPase expression and cellular sensitivity to TS inhibition in four human lung tumour cell lines. Sensitivity (5-day MTT assay) to the growth inhibitory effects of the non-polyglutamatable, specific quinazoline TS inhibitor ZD9331, varied up to 20-fold (IC 50 3–70 nM). TS protein expression correlated with TS activity (r2= 0.88 P= 0.05). Intracellular concentrations of drug following exposure to ZD9331 (1 μM, 24 h) varied by ~2-fold and dTTP pools decreased by > 80% in all cell lines. No clear associations across the cell lines between intracellular drug concentrations, TS activity/expression, or TTP depletion could be made. dUTPase activity varied 17-fold and correlated with dUTPase protein expression (r2= 0.94 P= 0.03). There was a striking variation in the amount of dUTP formed following exposure to ZD9331 (between 1.3 and 57 pmole 10–6cells) and was in general inversely associated with dUTPase activity. A large expansion in the dUTP pool was associated with increased sensitivity to a 24-h exposure to ZD9331 in A549 cells that have low dUTPase activity/expression. dUTPase expression and activity were elevated (approximately 3-fold) in two variants of a human lymphoblastoid cell line with acquired resistance to TS inhibitors, further suggesting an important role for this enzyme in TS inhibited cells. © 2000 Cancer Research Campaig