Reconciliation in Northern Ireland: The Value of Intergroup contact

Northern Ireland is still a country riven by segregation, caught between peace and reconciliation. Extensive survey research shows that intergroup contact has a key role to play in achieving reconciliation, whether through generic contact, cross-group friends (most effective) or indirect forms of contact. Segregation is most profound in education, but we show the benefits of contact in all mixed schools. A recent evaluation of a new Shared Education Programme (SEP), that provides children with the opportunity to study with and meet pupils from the other community, reveals reliable effects via promoting contact. The Northern Ireland Assembly’s support for SEP is based on sound psychological principles and robust research evidence.

Diagnostic value of increased sensitivity by massively parallel sequencing

Routine molecular diagnostics modalities are unable to confidently detect low frequency mutations (<5-15%) that may indicate response to targeted therapies. We confirm the presence of a low frequency NRAS mutation in a rectal cancer patient using massively parallel sequencing when previous Sanger sequencing results proved negative and Q-PCR testing inconclusive. There is increasing evidence that these low frequency mutations may confer resistance to anti-EGFR therapy. In view of negative/inconclusive Sanger sequencing and Q-PCR results for NRAS mutations in a KRAS wt rectal case, the diagnostic biopsy and 4 distinct subpopulations of cells in the resection specimen after conventional chemo/radiotherapy were massively parallel sequenced using the Ion Torrent PGM. DNA was derived from FFPE rectal cancer tissue and amplicons produced using the Cancer Hotspot Panel V2 and sequenced using semiconductor technology. NRAS mutations were observed at varying frequencies in the patient biopsy (12.2%) and all four subpopulations of cells in the resection with an average frequency of 7.3% (lowest 2.6%). The results of the NGS also provided the mutational status of 49 other genes that may have prognostic or predictive value, including KRAS and PIK3CA. NGS technology has been postulated in diagnostics because of its capability to generate results in large panels of clinically meaningful genes in a cost-effective manner. This case illustrates another potential advantage of this technology: its use for detecting low frequency mutations that may influence therapeutic decisions in cancer treatment.

Predictive Value of Depressive Symptoms for All-Cause Mortality: Findings From the PRIME Belfast Study Examining the Role of Inflammation and Cardiovascular Risk Markers

OBJECTIVES: To improve understanding about the potential underlying biological mechanisms in the link between depression and all-cause mortality and to investigate the role that inflammatory and other cardiovascular risk factors may play in the relationship between depressive symptoms and mortality.

METHODS: Depression and blood-based biological markers were assessed in the Belfast PRIME prospective cohort study (N = 2389 men, aged 50-59 years) in which participants were followed up for 18 years. Depression was measured using the 10-item Welsh Pure Depression Inventory. Inflammation markers (C-reactive protein [CRP], neopterin, interleukin [IL]-1 receptor antagonist [IL-1Ra], and IL-18) and cardiovascular-specific risk factors (N-terminal pro-b-type natriuretic peptide, midregion pro-atrial natriuretic peptide, midregion pro-adrenomedullin, C-terminal pro-endothelin-1 [CT-proET]) were obtained at baseline. We used Cox proportional hazards modeling to examine the association between depression and biological measures in relation to all-cause mortality and explore the mediating effects.

RESULTS: During follow-up, 418 participants died. Higher levels of depressive symptoms were associated with higher levels of CRP, IL-1Ra, and CT-proET. After adjustment for socioeconomic and life-style risk factors, depressive symptoms were significantly associated with all-cause mortality (hazard ratio = 1.10 per scale unit, 95% confidence interval = 1.04-1.16). This association was partly explained by CRP (7.3%) suggesting a minimal mediation effect. IL-1Ra, N-terminal pro-b-type natriuretic peptide, midregion pro-atrial natriuretic peptide, midregion pro-adrenomedullin, and CT-proET contributed marginally to the association between depression and subsequent mortality.

CONCLUSIONS: Inflammatory and cardiovascular risk markers are associated with depression and with increased mortality. However, depression and biological measures show additive effects rather than a pattern of meditation of biological factors in the association between depression and mortality.

The value of tests in the diagnosis and management of glaucoma.

PURPOSE:

To assess the noneconomic value of tests used in the diagnosis and management of glaucoma, and explore the contexts and factors that determine such value.

DESIGN:

Perspective.

METHODS:

Selected articles from primary and secondary sources were reviewed and interpreted in the context of the authors' clinical and research experience, influenced by our perspectives on the tasks of reducing the global problem of irreversible blindness caused by glaucoma. The value of any test used in glaucoma is addressed by 3 questions regarding: its contexts, its kind of value, and its implicit or explicit benefits.

RESULTS:

Tonometry, slit-lamp gonioscopy, and optic disc evaluation remain the foundation of clinic-based case finding, whether in areas of more or less abundant resources. In resource-poor areas, there is urgency in identifying patients at risk for severe functional loss of vision; screening strategies have proven ineffective, and efforts are hindered by the inadequate allocation of support. In resource-abundant areas, the wider spectrum of glaucoma is addressed, with emphasis on early detection of structural changes of little functional consequence; these are increasingly the focus of new and expensive technologies whose clinical value has not been established in longitudinal and population-based studies. These contrasting realities in part reflect differences among the value ascribed, often implicitly, to the tests used in glaucoma.

CONCLUSIONS:

The value of any test is determined by 3 aspects: its context of usage; its comparative worth and to whom its benefit accrues; and how we define historically what we are testing. These multiple factors