Judges, Conflict, and the Past

Drawing upon interviews with senior judicial figures in Northern Ireland, South Africa and elsewhere, this article considers the role of the judiciary in a political conflict.1 Using the socio-legal literature on judicial performance and audience as well as transitional justice, the article argues that judges in Northern Ireland ‘performed’ to a number of ‘imagined’ audiences including Parliament, ‘the public’ and their judicial peers - all of which it is argued shaped their view of the judicial role. In light of ongoing efforts to deal with the past in the jurisdiction, and the experiences of other transitional societies, the article argues that the judiciary can and should engage in a mature, reflexive and, where appropriate, self-critical examination of the good and bad of their own institutional history during the conflict. It also argues that such a review of judicial performance requires an external audience in order to encourage the judiciary to see truth beyond the limits of legalism.

Authority, Nationality, and Minorities

Prominent normative theories for accommodating minority national groups appeal to the value of national cultures and/or the psychology of group recognition. This article aims to show that an argument from political authority provides a better justification. Building on Joseph Raz's theory of authority, the article argues that members of minority national groups are disadvantaged in relation to their majority counterparts under standard democratic institutions; such institutions do not provide minority national groups with comparable access to the conditions for legitimate political authority. Constitutional arrangements for accommodating minority national groups—such as territorial self-government or power-sharing—are justified insofar as they might offset this disadvantage.

Refining the Chronology of the Neolithic Settlement at Pool, Sanday, Orkney: Implications for the Emergence and Development of Grooved Ware

New radiocarbon dates for the Neolithic settlement at Pool on Sanday, Orkney, are interpreted in a formal chronological framework. Phases 2.2 and 2.3, during which flat-based Grooved Ware pottery with incised decoration developed, have been modelled as probably dating to between the 31st and 28th centuries cal bc. There followed a hiatus of a century or so, before the resumption of occupation in Phase 3, which has a different Grooved Ware style featuring the use of applied decoration. This has been modelled as probably dating from the 26th to the 24th centuries cal bc. The implications of these results are discussed for the emergence and development of Grooved Ware, and for the trajectory of settlement and monumentality on Sanday.

Genome-wide association study for sight-threatening diabetic retinopathy reveals association with genetic variation near the GRB2 gene

AIMS/HYPOTHESIS: Diabetic retinopathy is a serious complication of diabetes mellitus and can lead to blindness. A genetic component, in addition to traditional risk factors, has been well described although strong genetic factors have not yet been identified. Here, we aimed to identify novel genetic risk factors for sight-threatening diabetic retinopathy using a genome-wide association study.

METHODS: Retinopathy was assessed in white Australians with type 2 diabetes mellitus. Genome-wide association analysis was conducted for comparison of cases of sight-threatening diabetic retinopathy (n = 336) with diabetic controls with no retinopathy (n = 508). Top ranking single nucleotide polymorphisms were typed in a type 2 diabetes replication cohort, a type 1 diabetes cohort and an Indian type 2 cohort. A mouse model of proliferative retinopathy was used to assess differential expression of the nearby candidate gene GRB2 by immunohistochemistry and quantitative western blot.

RESULTS: The top ranked variant was rs3805931 with p = 2.66 × 10(-7), but no association was found in the replication cohort. Only rs9896052 (p = 6.55 × 10(-5)) was associated with sight-threatening diabetic retinopathy in both the type 2 (p = 0.035) and the type 1 (p = 0.041) replication cohorts, as well as in the Indian cohort (p = 0.016). The study-wide meta-analysis reached genome-wide significance (p = 4.15 × 10(-8)). The GRB2 gene is located downstream of this variant and a mouse model of retinopathy showed increased GRB2 expression in the retina.

CONCLUSIONS/INTERPRETATION: Genetic variation near GRB2 on chromosome 17q25.1 is associated with sight-threatening diabetic retinopathy. Several genes in this region are promising candidates and in particular GRB2 is upregulated during retinal stress and neovascularisation.

A coactivator role of CARM1 in the dysregulation of β-catenin activity in colorectal cancer cell growth and gene expression

Aberrant activation of Wnt/β-catenin signaling, resulting in the expression of Wnt-regulated oncogenes, is recognized as a critical factor in the etiology of colorectal cancer. Occupancy of β-catenin at promoters of Wnt target genes drives transcription, but the mechanism of β-catenin action remains poorly understood. Here, we show that CARM1 (coactivator-associated arginine methyltransferase 1) interacts with β-catenin and positively modulates β-catenin-mediated gene expression. In colorectal cancer cells with constitutively high Wnt/β-catenin activity, depletion of CARM1 inhibits expression of endogenous Wnt/β-catenin target genes and suppresses clonal survival and anchorage-independent growth. We also identified a colorectal cancer cell line (RKO) with a low basal level of β-catenin, which is dramatically elevated by treatment with Wnt3a. Wnt3a also increased the expression of a subset of endogenous Wnt target genes, and CARM1 was required for the Wnt-induced expression of these target genes and the accompanying dimethylation of arginine 17 of histone H3. Depletion of β-catenin from RKO cells diminished the Wnt-induced occupancy of CARM1 on a Wnt target gene, indicating that CARM1 is recruited to Wnt target genes through its interaction with β-catenin and contributes to transcriptional activation by mediating events (including histone H3 methylation) that are downstream from the actions of β-catenin. Therefore, CARM1 is an important positive modulator of Wnt/β-catenin transcription and neoplastic transformation, and may thereby represent a novel target for therapeutic intervention in cancers involving aberrantly activated Wnt/β-catenin signaling.

Extent and mechanism of phase separation during the extrusion of calcium phosphate pastes

The aim of this study was to increase understanding of the mechanism and dominant drivers influencing phase separation during ram extrusion of calcium phosphate (CaP) paste for orthopaedic applications. The liquid content of extrudate was determined, and the flow of liquid and powder phases within the syringe barrel during extrusion were observed, subject to various extrusion parameters. Increasing the initial liquid-to-powder mass ratio, LPR, (0.4-0.45), plunger rate (5-20 mm/min), and tapering the barrel exit (45°-90°) significantly reduced the extent of phase separation. Phase separation values ranged from (6.22 ± 0.69 to 18.94 ± 0.69 %). However altering needle geometry had no significant effect on phase separation. From powder tracing and liquid content determination, static zones of powder and a non-uniform liquid distribution was observed within the barrel. Measurements of extrudate and paste LPR within the barrel indicated that extrudate LPR remained constant during extrusion, while LPR of paste within the barrel decreased steadily. These observations indicate the mechanism of phase separation was located within the syringe barrel. Therefore phase separation can be attributed to either; (1) the liquid being forced downstream by an increase in pore pressure as a result of powder consolidation due to the pressure exerted by the plunger or (2) the liquid being drawn from paste within the barrel, due to suction, driven by dilation of the solids matrix at the barrel exit. Differentiating between these two mechanisms is difficult; however results obtained suggest that suction is the dominant phase separation mechanism occurring during extrusion of CaP paste.

Studying Gender in Conference Talks -- data from the 223rd meeting of the American Astronomical Society

We present a study on the gender balance, in speakers and attendees, at the recent major astronomical conference, the American Astronomical Society meeting 223, in Washington, DC. We conducted an informal survey, yielding over 300 responses by volunteers at the meeting. Each response included gender data about a single talk given at the meeting, recording the gender of the speaker and all question-askers. In total, 225 individual AAS talks were sampled. We analyze basic statistical properties of this sample. We find that the gender ratio of the speakers closely matched the gender ratio of the conference attendees. The audience asked an average of 2.8 questions per talk. Talks given by women had a slightly higher number of questions asked (3.2$\pm$0.2) than talks given by men (2.6$\pm$0.1). The most significant result from this study is that while the gender ratio of speakers very closely mirrors that of conference attendees, women are under-represented in the question-asker category. We interpret this to be an age-effect, as senior scientists may be more likely to ask questions, and are more commonly men. A strong dependence on the gender of session chairs is found, whereby women ask disproportionately fewer questions in sessions chaired by men. While our results point to laudable progress in gender-balanced speaker selection, we believe future surveys of this kind would help ensure that collaboration at such meetings is as inclusive as possible.

Closed circuit rebreathing to achieve inert gas wash-in for multiple breath wash-out

Multiple breath wash-out (MBW) testing requires prior wash-in of inert tracer gas. Wash-in efficiency can be enhanced by a rebreathing tracer in a closed circuit. Previous attempts to deploy this did not account for the impact of CO2 accumulation on patients and were unsuccessful. We hypothesised that an effective rebreathe wash-in could be delivered and it would not alter wash-out parameters. Computer modelling was used to assess the impact of the rebreathe method on wash-in efficiency. Clinical testing of open and closed circuit wash-in–wash-out was performed in healthy controls and adult patients with cystic fibrosis (CF) using a circuit with an effective CO2 scrubber and a refined wash-in protocol. Wash-in efficiency was enhanced by rebreathing. There was no difference in mean lung clearance index between the two wash-in methods for controls (6.5 versus 6.4; p=0.2, n=12) or patients with CF (10.9 versus 10.8; p=0.2, n=19). Test time was reduced by rebreathe wash-in (156 versus 230 s for CF patients, p<0.001) and both methods were well tolerated. End wash-in CO2 was maintained below 2% in most cases. Rebreathe–wash-in is a promising development that, when correctly deployed, reduces wash-in time and facilitates portable MBW testing. For mild CF, wash-out outcomes are equivalent to an open circuit.