Establishing the ‘Truth’ of the Matter: Confessional Reflexivity as Introspection and Avowal

The conceptualisation of reflexivity commonly found in social anthropology deploys the term as if it were both a ‘virtuous’ mechanism of self‐reflection and an ethical technique of truth telling, with reflexivity frequently deployed as an moral practice of introspection and avowal. Further, because reflexivity is used as a methodology for constructing the authority of ethnographic accounts, reflexivity in anthropology has come to closely resemble Foucault’s descriptions of confession. By discussing Lynch’s (2000) critical analysis of reflexivity as an ‘academic virtue’, I consider his argument through the lens of my own concept of ‘confessional reflexivity’. While supporting Lynch’s diagnosis of the ‘problem of reflexivity’, I attempt to critique his ethnomethodological cure as essentialist, I conclude that a way forward might be found by blending Foucault’s (1976, 1993) theory of confession with Bourdieu’s (1992) theory of ‘epistemic reflexivity’.

Remembering forwards: or how to live together in the future with divided memories

Memory is thought to be about the past. The past is a problem in conflict transformation. This lecture suggests memory can also be about the future. It introduces the notion of remembering forwards, which is contrasted with remembering backwards. The distinction between these two forms of remembering defines the burden of memory in post-conflict societies generally and specifically in Ireland. In societies emerging out of conflict, where divided memories in part constituted the conflict, social memory privileges remembering backward. Collective and personal memories elide within social memory to perpetuate divided group identities and contested personal narratives. Above all, social memory works to arbitrate the future, by predisposing an extreme memory culture that locks people into the past. Forgetting the past is impossible and undesirable. What is needed in societies emerging out of conflict is to be released from the hold that oppressive and haunting memories have over people. This lecture will suggest that this is found in the idea of remembering forwards. This is not the same as forgetting. It is remembering to cease to remember oppressive and haunting memories. It does not involve non-remembrance but active remembering: remembering to cease to remember the past. While the past lives in us always, remembering forwards assists us in not living in the past. Remembering forwards thus allows us to live in tolerance in the future despite the reality that divided memories endure and live on. The lecture further argues that these enduring divided memories need to be reimagined by the application of truth, tolerance, togetherness and trajectory. The lecture suggests that it is through remembering forwards with truth, tolerance, togetherness and trajectory that people in post-conflict societies can inherit the future despite their divided pasts and live in tolerance in the midst of contested memories.

FcγRIIa and FcγRIIIa polymorphisms and cetuximab benefit in the microscopic disease

Purpose: FcγR polymorphisms have been reported to enhance the immune-mediated effects of cetuximab in metastatic colorectal cancer. There are no data on the relationship between these polymorphisms and cetuximab in the early-stage setting. We performed a pharmacogenomic analysis of EXPERT-C, a randomized phase II trial of neoadjuvant CAPOX followed by chemoradiotherapy, surgery, and adjuvant CAPOX ± cetuximab in high-risk, locally advanced rectal cancer.

Experimental Design: FcγRIIa-H131R and FcγRIIIa-V158F polymorphisms were analyzed on DNA from peripheral blood samples. Kaplan–Meier method and Cox regression analysis were used to calculate survival estimates and compare treatment arms.

Results: Genotyping was successfully performed in 105 of 164 (64%) patients (CAPOX = 54, CAPOX-C = 51). No deviation from the Hardy–Weinberg equilibrium or association of these polymorphisms with tumor RAS status was observed. FcγRIIa-131R (HR, 0.38; P = 0.058) and FcγRIIIa-158F alleles (HR, 0.21; P = 0.007) predicted improved progression-free survival (PFS) in patients treated with cetuximab. In the CAPOX-C arm, carriers of both 131R and 158F alleles had a statistically significant improvement in PFS (5 years: 78.4%; HR, 0.22; P = 0.002) and overall survival (OS; 5 years: 86.4%; HR, 0.24; P = 0.018) when compared with patients homozygous for 131H and/or 158V (5-year PFS: 35.7%; 5-year OS: 57.1%). An interaction between cetuximab benefit and 131R and 158F alleles was found for PFS (P = 0.017) and remained significant after adjusting for prognostic variables (P = 0.003).

Conclusion: This is the first study investigating FcγRIIa and FcγRIIIa polymorphisms in patients with early-stage colorectal cancer treated with cetuximab. We showed an increased clinical benefit from cetuximab in the presence of 131R and 158F alleles.

Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer's disease.

Genome-wide association studies (GWAS) have identified several risk variants for late-onset Alzheimer's disease (LOAD)1, 2. These common variants have replicable but small effects on LOAD risk and generally do not have obvious functional effects. Low-frequency coding variants, not detected by GWAS, are predicted to include functional variants with larger effects on risk. To identify low-frequency coding variants with large effects on LOAD risk, we carried out whole-exome sequencing (WES) in 14 large LOAD families and follow-up analyses of the candidate variants in several large LOAD case–control data sets. A rare variant in PLD3 (phospholipase D3; Val232Met) segregated with disease status in two independent families and doubled risk for Alzheimer’s disease in seven independent case–control series with a total of more than 11,000 cases and controls of European descent. Gene-based burden analyses in 4,387 cases and controls of European descent and 302 African American cases and controls, with complete sequence data for PLD3, reveal that several variants in this gene increase risk for Alzheimer’s disease in both populations. PLD3 is highly expressed in brain regions that are vulnerable to Alzheimer’s disease pathology, including hippocampus and cortex, and is expressed at significantly lower levels in neurons from Alzheimer’s disease brains compared to control brains. Overexpression of PLD3 leads to a significant decrease in intracellular amyloid-β precursor protein (APP) and extracellular Aβ42 and Aβ40 (the 42- and 40-residue isoforms of the amyloid-β peptide), and knockdown of PLD3 leads to a significant increase in extracellular Aβ42 and Aβ40. Together, our genetic and functional data indicate that carriers of PLD3 coding variants have a twofold increased risk for LOAD and that PLD3 influences APP processing. This study provides an example of how densely affected families may help to identify rare variants with large effects on risk for disease or other complex traits.

'Truth, Ethics and Efficacy in the Training of Actors for Role Play'

Krysia M. Yardley-Matwiejczuk has addressed the clinical and psychological implications of role-play (Role Play: Theory and Practice, Sage Publications, 1997) and Judith Ackroyd has thoroughly reassessed the place of roleplay in education (Role Reconsidered, Trentham Books, 2004). But there has been no systematic analysis of the implications for actor training of this growing area of employment. This paper interrogates some of the implications of role-play for actor trainers, particularly in relation to the need for a clear ethical framework governing spontaneous performance in non-theatrical environments. The paper also suggests guidelines on ‘distancing’ and ‘presencing’ techniques to equip actors to cope with the unpredictability of role play-based performance.

Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA)

BACKGROUND: In this study we aimed to evaluate the role of a SNP in intron I of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers.

Non-uptake of predictive genetic testing for BRCA1/2 among relatives of known carriers: Attributes, cancer worry, and barriers to testing in a multicenter clinical cohort

BRCA1/2 test decliners/deferrers have received almost no attention in the literature and this is the first study of this population in the United Kingdom. The aim of this multicenter study is to examine the attributes of a group of individuals offered predictive genetic testing for breast/ovarian cancer predisposition who did not wish to proceed with testing at the time of entry into this study. This forms part of a larger study involving 9 U.K. centers investigating the psychosocial impact of predictive genetic testing for BRCA1/2. Cancer worry and reasons for declining or deferring BRCA1/2 predictive genetic testing were evaluated by questionnaire following genetic counseling. A total of 34 individuals declined the offer of predictive genetic testing. Compared to the national cohort of test acceptors, test decliners are significantly younger. Female test decliners have lower levels of cancer worry than female test acceptors. Barriers to testing include apprehension about the result, traveling to the genetics clinic, and taking time away from work/family. Women are more likely than men to worry about receiving less screening if found not to be a carrier. The findings do not indicate that healthy BRCA1/2 test decliners are a more vulnerable group in terms of cancer worry. However, barriers to testing need to be discussed in genetic counseling.