Deliberately infecting healthy volunteers with malaria parasites: Perceptions and experiences of participants and other stakeholders in a Kenyan-based malaria infection study

Controlled human malaria infection (CHMI) studies involve the deliberate infection of healthy volunteers with malaria parasites under controlled conditions to study immune responses and/or test drug or vaccine efficacy. An empirical ethics study was embedded in a CHMI study at a Kenyan research programme to explore stakeholders’ perceptions and experiences of deliberate infection and moral implications of these. Data for this qualitative study were collected through focus group discussions, in-depth interviews and non-participant observation. Sixty-nine participants were involved, including CHMI study volunteers, community representatives and research staff. Data were managed using QSR Nvivo 10 and analysed using an inductive-deductive approach, guided by ethics literature. CHMI volunteers had reasonable understanding of the study procedures. Decisions to join were influenced by study incentives, trust in the research institution, their assessment of associated burdens and motivation to support malaria vaccine development. However, deliberate malaria infection was a highly unusual research strategy for volunteers, community representatives and some study staff. Volunteers’ experiences of physical, emotional and social burdens or harms were often greater than anticipated initially, and fluctuated over time, related to specific procedures and events. Although unlikely to deter volunteers' participation in similar studies in furture, we argue that the dissonance between level of understanding of the burdens involved and actual experiences are morally relevant in relation to community engagement, informed consent processes, and ongoing support for volunteers and research staff. We further argue that ethics oversight of CHMI studies should take account of these issues in deciding whether consent, engagement and the balance of benefits and harms are reasonable in a given context.     

Multiculturalism in crisis: A postmodern perspective on Canada

Using a modified postmodern perspective, Canada's policy of multiculturalism and the emphasis upon ‘unity within diversity’ are related to the theme of globalization and the development of ‘a new world order’. It is argued that Canada is not unique in its efforts to come to terms with the contradictions and conflicts generated by postindustrialism and the realignment of superpowers. Questions of identity, collective self‐determination and the problematic relation between universalism and particularism, in relation to sovereignty, legitimacy, human rights and participation are explored.     

Characterization of tubule and monomer derived from VP4 protein of infectious bursal disease virus

The VP4 protein of infectious bursal disease virus (IBDV) is a serine protease that processes the polyprotein for viral assembly. VP4 has been found to associate primarily with type II IBDV tubules that are 24 nm in diameter. In this study, a chimeric VP4, assigned as HS1VP4, was constructed with a VP4-autocleavage site inserted between the N-terminal His-tag and the VP4 sequence. The results showed that the VP4 forms tubules after the self-cleavage of HS1VP4 when expressed in Escherichia coli. Furthermore, a deletion of 28 amino acids at the C-terminus of VP4 resulted in monomers and dimers instead of tubule formation; mutants of S652A and K692A at active site destroyed the activity. The endopeptidase activity of these monomers and dimers was approximately 12.5 times higher than that of VP4 tubules. Additionally, the formation of tubules inhibited VP4 protease activity, as demonstrated through in vitro assays. The production and characterization of monomers or dimers that have greater endopeptidase activity and protease activity than tubules can provide further insight into VP4 tubule assembly and the regulation of VP4 activity in host cells; this insight will facilitate the development of new anti-IBDV strategies.     

Ensembles of endothelial and mural cells promote angiogenesis in prenatal human brain

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Anatomically-based skeletal coordinate systems for use with impact biomechanics data intended for anthropomorphic test device development

Post-mortem human subjects (PMHS) are frequently used to characterize biomechanical response and injury tolerance of humans to various types of loading by means of instrumentation installed directly on the skeleton. Data extracted from such tests are often used to develop and validate anthropomorphic test devices (ATDs), which function as human surrogates in tests for injury assessment. Given that the location and orientation of installed instrumentation differs between subjects, nominally similar measurements made on different PMHS must be transformed to standardized, skeletal-based local coordinate systems (LCS) before appropriate data comparisons can be made. Standardized PMHS LCS that correspond to ATD instrumentation locations and orientations have not previously been published. This paper introduces anatomically-defined PMHS LCS for body regions in which kinematic measurements are made using ATDs. These LCS include the head, sternum, single vertebrae, pelvis, femurs (distal and proximal), and tibiae (distal and proximal) based upon skeletal landmarks extracted from whole body CT scans. The proposed LCS provide a means to standardize the reporting of PMHS data, and facilitate both the comparison of PMHS impact data across institutions and the application of PMHS data to the development and validation of ATDs.