"On the Spot": travelling artists and Abolitionism, 1770-1830

Until recently the visual culture of Atlantic slavery has rarely been critically scrutinised. Yet in the first decades of the nineteenth century slavery was frequently represented by European travelling artists, often in the most graphic, sometimes voyeuristic, detail. This paper examines the work of several itinerant artists, in particular Augustus Earle (1793-1838) and Agostino Brunias (1730–1796), whose very mobility along the edges of empire was part of a much larger circulatory system of exchange (people, goods and ideas) and diplomacy that characterised Europe’s Age of Expansion. It focuses on the role of the travelling artist, and visual culture more generally, in the development of British abolitionism between 1770 and 1830. It discusses the broad circulation of slave imagery within European culture and argues for greater recognition of the role of such imagery in the abolitionist debates that divided Britain. Furthermore, it suggests that the epistemological authority conferred on the travelling artist—the quintessential eyewitness—was key to the rhetorical power of his (rarely her) images. Artists such as Earle viewed the New World as a boundless source of fresh material that could potentially propel them to fame and fortune. Johann Moritz Rugendas (1802-1858), on the other hand, was conscious of contributing to a global scientific mission, a Humboldtian imperative that by the 1820s propelled him and others to travel beyond the traditional itinerary of the Grand Tour. Some artists were implicated in the very fabric of slavery itself, particularly those in the British West Indies such as William Clark (working 1820s) and Richard Bridgens (1785-1846); others, particularly those in Brazil, expressed strong abolitionist sentiments. Fuelled by evangelical zeal to record all aspects of the New World, these artists recognised the importance of representing the harsh realities of slave life. Unlike those in the metropole who depicted slavery (most often in caustic satirical drawings), many travelling artists believed strongly in the evidential value of their images, a value attributed to their global mobility. The paper examines the varied and complex means by which visual culture played a significant and often overlooked role in the political struggles that beset the period

Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis

Rationale: T-cell responses during tuberculosis (TB) help contain Mycobacterium tuberculosis in vivo but also cause collateral damage to host tissues. Immune regulatory mechanisms may limit this immunopathology, and suppressed cellular immune responses in patients with TB suggest the presence of regulatory activity. CD4+CD25high regulatory T cells mediate suppressed cellular immunity in several chronic infections but have not been described in TB.Objective: To determine whether regulatory T cells are increased in patients with TB and whether they suppress cellular immune responses.Methods: We compared the frequency of circulating regulatory T cells in 27 untreated patients with TB and 23 healthy control subjects using two specific markers: cell-surface CD25 expression and FoxP3 mRNA expression in peripheral blood mononuclear cells.Measurements and Main Results: We detected a threefold increase in the frequency of CD4+CD25high T cells (p < 0.001) and a 2.2-fold increase in FoxP3 expression (p = 0.006) in patients with TB, and there was a positive correlation between these markers (r = 0.58, p < 0.001). Increased expression of interleukin-10 and transforming growth factor-beta1 mRNA was also detected in patients with TB but did not correlate with regulatory T-cell markers. Ex vivo depletion of CD4+CD25high cells from peripheral blood mononuclear cells resulted in increased numbers of M. tuberculosis antigen–specific IFN-{gamma}–producing T cells in seven of eight patients with TB (p = 0.005). Finally, FoxP3 expression was increased 2.3-fold in patients with extrapulmonary TB compared with patients with purely pulmonary TB (p = 0.01) and was amplified 2.6-fold at disease sites relative to blood (p = 0.043).Conclusions: Regulatory T cells are expanded in patients with TB and may contribute to suppression of Th1-type immune responses

Dynamic relationship between IFN-gamma and IL-2 profile of Mycobacterium tuberculosis-specific T cells and antigen load

Distinct IFN-gamma and IL-2 profiles of Ag-specific CD4(+) T cells have recently been associated with different clinical disease states and Ag loads in viral infections. We assessed the kinetics and functional profile of Mycobacterium tuberculosis Ag-specific T cells secreting IFN-gamma and IL-2 in 23 patients with untreated active tuberculosis when bacterial and Ag loads are high and after curative treatment, when Ag load is reduced. The frequencies of M. tuberculosis Ag-specific IFN-gamma-secreting T cells declined during 28 mo of follow-up with an average percentage decline of 5.8% per year (p = 0.005), while the frequencies of Ag-specific IL-2-secreting T cells increased during treatment (p = 0.02). These contrasting dynamics for the two cytokines led to a progressive convergence of the frequencies of IFN-gamma- and IL-2-secreting cells over 28 mo. Simultaneous measurement of IFN-gamma and IL-2 secretion at the single-cell level revealed a codominance of IFN-gamma-only secreting and IFN-gamma/IL-2 dual secreting CD4(+) T cells in active disease that shifted to dominance of IFN-gamma/IL-2-secreting CD4(+) T cells and newly detectable IL-2-only secreting CD4(+) T cells during and after treatment. These distinct T cell functional signatures before and after treatment suggest a novel immunological marker of mycobacterial load and clinical status in tuberculosis that now requires validation in larger prospective studies

Improved diagnostic evaluation of suspected tuberculosis

Background: The role of new T-cell–based blood tests for tuberculosis in the diagnosis of active tuberculosis is unclear.Objective: To compare the performance of 2 interferon-? assays and tuberculin skin testing in adults with suspected tuberculosis.Design: Prospective study conducted in routine practice.Setting: 2 urban hospitals in the United Kingdom.Patients: 389 adults, predominantly of South Asian and black ethnicity, with moderate to high clinical suspicion of active tuberculosis.Intervention: Tuberculin skin testing, the enzyme-linked immunospot assay (ELISpot) incorporating early secretory antigenic target-6 and culture filtrate protein-10 (standard ELISpot), and ELISpot incorporating a novel antigen, Rv3879c (ELISpotPLUS) were performed during diagnostic assessment by independent persons who were blinded to results of the other test.Measurements: Sensitivity, specificity, predictive values, and likelihood ratios.Results: 194 patients had a final diagnosis of active tuberculosis, of which 79% were culture-confirmed. Sensitivity for culture confirmed and highly probable tuberculosis was 89% (95% CI, 84% to 93%) with ELISpotPLUS, 85% (CI, 79% to 90%) with standard ELISpot, 79% (CI, 72% to 85%) with 15-mm threshold tuberculin skin testing, and 83% (CI, 77% to 89%) with stratified thresholds of 15 and 10 mm in vaccinated and unvaccinated patients, respectively. The ELISpotPLUS assay was more sensitive than tuberculin skin testing with 15-mm cutoff points (P = 0.01) but not with stratified cutoff points (P = 0.10). The ELISpotPLUS assay had 4% higher diagnostic sensitivity than standard ELISpot (P = 0.02). Combined sensitivity of ELISpotPLUS and tuberculin skin testing was 99% (CI, 95% to 100%), conferring a negative likelihood ratio of 0.02 (CI, 0 to 0.06) when both test results were negative.Limitations: Local standards for tuberculin skin testing differed from others used internationally. The study sample included few immunosuppressed patients.Conclusion: The ELISpotPLUS assay is more sensitive than standard ELISpot and, when used in combination with tuberculin skin testing, enables rapid exclusion of active infection in patients with moderate to high pretest probability of tuberculosis

Evolutionary algorithms for practical sensor fault tolerant control

The Shaky Hand is a multi-input, multi-output laboratory demonstrator which is modelled on a village fete game. In the original, the aim is to guide, by hand, a wire loop along a wire which has been bent to form a meandering track, 'without touching the loop to the wire. In the original game, touching the hand-held loop against the wire track sets off a loud warning bell and the player loses. The thesis presents the research work associated with the quest for practical solutions to a generic problem: the correct operation of a fallible system. The work covers three distinct areas: modelling of the demonstrator, design and construction of a physical system, and evoiution of algorithms for control of the demonstrator in practice in the presence of sensor faults, using Cartesian Genetic Programming (CGP). The third area forms the core of the thesis. The key challenges in creating the virtual environment to train for generic sensor fault tolerant algorithms are considered and addressed. The evolved algorithms are analysed and then verified using the demonstrator in practice. The practical results showed that sensor fault tolerant control was successfully achieved

A mycolic acid–specific CD1-restricted T cell population contributes to acute and memory immune responses in human tuberculosis infection

Current tuberculosis (TB) vaccine strategies are largely aimed at activating conventional T cell responses to mycobacterial protein antigens. However, the lipid-rich cell wall of Mycobacterium tuberculosis (M. tuberculosis) is essential for pathogenicity and provides targets for unconventional T cell recognition. Group 1 CD1–restricted T cells recognize mycobacterial lipids, but their function in human TB is unclear and their ability to establish memory is unknown. Here, we characterized T cells specific for mycolic acid (MA), the predominant mycobacterial cell wall lipid and key virulence factor, in patients with active TB infection. MA-specific T cells were predominant in TB patients at diagnosis, but were absent in uninfected bacillus Calmette-Guérin–vaccinated (BCG-vaccinated) controls. These T cells were CD1b restricted, detectable in blood and disease sites, produced both IFN-γ and IL-2, and exhibited effector and central memory phenotypes. MA-specific responses contracted markedly with declining pathogen burden and, in patients followed longitudinally, exhibited recall expansion upon antigen reencounter in vitro long after successful treatment, indicative of lipid-specific immunological memory. T cell recognition of MA is therefore a significant component of the acute adaptive and memory immune response in TB, suggesting that mycobacterial lipids may be promising targets for improved TB vaccines

Self‐Motion and Cognition: Plato's Theory of the Soul

I argue that Plato believes that the soul must be both the principle of motion and the subject of cognition because it moves things specifically by means of its thoughts. I begin by arguing that the soul moves things by means of such acts as examination and deliberation, and that this view is developed in response to Anaxagoras. I then argue that every kind of soul enjoys a kind of cognition, with even plant souls having a form of Aristotelian discrimination (krisis), and that there is therefore no completely unintelligent, evil soul in the cosmos that can explain disorderly motions; as a result, the soul is not the principle of all motion but only motion in the cosmos after it has been ordered by the Demiurge