Practical and Ethical Problems with 'Vulnerability'

This project analyzes the concept of vulnerability and the way that it is applied as a label in the context of human subject research. Vulnerability as a concept represents concern for an individual's or group's acute inability to protect her or their own interests. In the research context, this concept is applied as a label across large populations in an attempt to signify a need for added protections when these populations are enrolled in research because of the heightened susceptibility of these groups to harms, wrongs, or exploitation. Although there are legitimate reasons for extending heightened protections to particular individuals, the way the concept is currently applied in the research context fails to protect all those who are in need of protections, and furthermore, causes harm or wrongs individuals and those populations so-termed 'vulnerable'. The label is too broad, and tends to extend protections to those who are not in need of them to their potential detriment. Furthermore, the label fails to draw attention to the manner in which these groups are vulnerable and thus appropriate and adequate protections may not be offered. The label of 'vulnerability' can also carry with it a stigma, which may be internalized by members of these vulnerable populations. Instead of conceptualizing vulnerability as an individual's or group's inability to protect her or their own interests due to some feature of those so labeled, vulnerability should be conceptualized in a way that does not obscure the relational features of the concept — i.e., that the type of vulnerability of interest in research frequently is the result of relationships of power, and research protections should adopt a framework based on such a conceptualization. The focus ought to be on those features or situational characteristics that are likely to override an individual's assertion of her own interests. This approach would avoid the situating of the inability to protect one's own interests within the individual, and would allow for a practical enactment of protections which serve everyone equally when they are in situations of experiencing vulnerability in relation to a particular other or institution

Killing of Escherichia coli by Crohn's Disease Monocyte-derived Macrophages and Its Enhancement by Hydroxychloroquine and Vitamin D

BACKGROUND: Crohn's disease (CD) is associated with defective innate immunity, including impaired neutrophil chemotaxis, and mucosal invasion by bacteria, particularly adherent and invasive Escherichia coli that replicate inside macrophage phagolysosomes. We compared CD and healthy control (HC) macrophages for their abilities to kill E. coli and generate neutrophil chemoattractants and also assessed the effects of hydroxychloroquine (HCQ) and vitamin D on killing of phagocytosed E. coli. METHODS: Peripheral blood monocyte-derived macrophages from CD and HC were compared for bacterial killing and generation of neutrophil chemoattractants in response to CD-derived E. coli. Escherichia coli replication was also assessed in the presence and absence of HCQ, alone and with antibiotics, and vitamin D. RESULTS: Monocyte-derived macrophages from patients with CD were similar to HC in allowing replication of phagocytosed CD-derived E. coli: HM605 {CD: N = 10, mean fold replication in 3 hr = 1.08 (95% confidence interval [CI], 0.39–1.78); HC: N = 9, 1.50 (95% CI, 1.02–1.97); P = 0.15} and also in generation of neutrophil chemoattractants in response to E. coli (mean fold chemotaxis relative to control: CD = 2.55 [95% CI, 2.31–2.80]; HC = 2.65 [95% CI, 2.46–2.85], P = 0.42). HCQ and 1,25 OH(2)-vitamin D(3) both caused dose-dependent inhibition of intramacrophage E. coli replication 3-hour postinfection; HCQ: 73.9% inhibition (P < 0.001) at 1 μg/mL, accompanied by raised intraphagosomal pH, and 1,25 OH(2)-vitamin D(3): 80.7% inhibition (P < 0.05) at 80 nM. HCQ had synergistic effects with doxycycline and ciprofloxacin. CONCLUSIONS: CD and HC macrophages perform similarly in allowing replication of phagocytosed E. coli and generating neutrophil chemoattractants. Replication of phagocytosed E. coli was substantially decreased by HCQ and vitamin D. These warrant further therapeutic trials in CD in combination with relevant antibiotics

Environmental isotope data: oxygen isotope concentration in precipitation in N-E Italy (Friuli Venezia Giulia)

Mineralogica et Petrografica Act