No evidence for linkage or association of neuregulin-1 (NRG1) with disease in the Irish study of high-density schizophrenia families (ISHDSF)

The neuregulin-1 gene (NRG1) at chromosome 8p21-22 has been implicated as a schizophrenia susceptibility gene in Icelandic, Scottish, Irish and mixed UK populations. The shared ancestry between these populations led us to investigate the NRG1 polymorphisms and appropriate marker haplotypes for linkage and/or association to schizophrenia in the Irish study of high-density schizophrenia families (ISHDSF). Neither single-point nor multi-point linkage analysis of NRG1 markers gave evidence for linkage independent of our pre-existing findings telomeric on 8p. Analysis of linkage disequilibrium (LD) across the 252 kb interval encompassing the 7 marker core Icelandic/Scottish NRG1 haplotype revealed two separate regions of modest LD, comprising markers SNP8NRG255133, SNP8NRG249130 and SNP8NRG243177 (telomeric) and microsatellites 478B14-428, 420M9-1395, D8S1810 and 420M9-116I12 (centromeric). From single marker analysis by TRANSMIT and FBAT we found no evidence for association with schizophrenia for any marker. Haplotype analysis for the three SNPs in LD region 1 and, separately, the four microsatellites in LD region 2 (analyzed in overlapping 2-marker windows), showed no evidence for overtransmission of specific haplotypes to affected individuals. We therefore conclude that if NRG1 does contain susceptibility alleles for schizophrenia, they impact quite weakly on risk in the ISHDSF.

De-linkage Processes and Grassroots Movements in Transitional Justice

Transitional justice literature has highlighted a negative relationship between enforced disappearances and reconciliation in post-conflict settings. Little attention has been paid to how human rights issues can become stepping-stones to reconciliation. The article explains the transformation of the Cypriot Committee on Missing Persons (CMP) from an inoperative body into a successful humanitarian forum, paving the way for the pro-rapprochement bi-communal grassroots mobilization of the relatives of the missing. By juxtaposing the experience of Cyprus with other societies confronting similar problems, the article shows how the issue of the missing can become a driving force for reconciliation. The findings indicate that a policy delinking humanitarian exhumations from the prospect of a wider political settlement facilitates positive transformation in protracted human rights problems and opens up a window of opportunity to grassroots actors.

Large panel-survey data demonstrated country-level and ethnic minority variation in consent for health record linkage

Objectives
To investigate individual, household and country variation in consent to health record linkage.

Study Design and Setting
Data from 50,994 individuals aged 16-74 years recruited to wave 1 of a large UK general purpose household survey (January 2009 – December 2010) were analysed using multi-level logistic regression models.

Results
Overall, 70.7% of respondents consented to record linkage. Younger age, marriage, tenure, car ownership and education were all significantly associated with consent, though there was little deviation from 70% in subgroups defined by these variables. There were small increases in consent rates in individuals with poor health when defined by self-reported long term limiting illness (adjusted OR 1.11; 95%CIs 1.06, 1.16), less so when defined by General Health Questionnaire score (adjusted OR=1.05; 95%CIs 1.00, 1.10), but the range in absolute consent rates between categories was generally less than 10%. Larger differences were observed for those of non-white ethnicity who were 38% less likely to consent (adjusted OR 0.62; 95%CIs 0.59, 0.66). Consent was higher in Scotland than England (adjusted OR 1.17; 95%CIs 1.06, 1.29) but lower in Northern Ireland (adjusted OR 0.56; 95%CIs 0.50, 0.63).

Conclusion
The modest overall level of systematic bias in consent to record linkage provides reassurance for record linkage potential in general purpose household surveys. However, the low consent rates amongst non-white ethnic minority survey respondents will further compound their low survey participation rates. The reason for the country-level variation requires further study.

Complete nucleotide sequence of φCHU: A Luz24likevirus infecting Pseudomonas aeruginosa and displaying a unique host range

A complete nucleotide sequence of the new Pseudomonas aeruginosa Luz24likevirus phiCHU was obtained. This virus was shown to have a unique host range whereby it grew poorly on the standard laboratory strain PAO1, but infected 26 of 46 clinical isolates screened, and strains harboring IncP2 plasmid pMG53. It was demonstrated that phiCHU has single strand interruptions in its genome. Analysis of the phiCHU genome also suggested that recombination event(s) participated in the evolution of the leftmost portion of the genome, presumably encoding early genes.

Complete control of high-harmonic generation for high average power applications

We present a new dual-gas multi-jet HHG source which can be perfectly controlled via phasematching of the long and short trajectory contributions and is applicable for high average power driver laser systems. © 2011 Optical Society of America.

Does conurbation affect the risk of poor mental health? A population based record linkage study

To determine if urban residence is associated with an increased risk of anxiety/depression independent of psychosocial stressors, concentrated disadvantage or selective migration between urban and rural areas, this population wide record-linkage study utilised data on receipt of prescription medication linked to area level indicators of conurbation and disadvantage. An urban/rural gradient in anxiolytic and antidepressant use was evident that was independent of variation in population composition. This gradient was most pronounced amongst disadvantaged areas. Migration into increasingly urban areas increased the likelihood of medication. These results suggest increasing conurbation is deleterious to mental health, especially amongst residents of deprived areas

The Complete Works of John Milton: Volume III: The Shorter Poems (826pp.)

Stephen B. Dobranski, Milton Quarterly 49.3 (October, 2015), 181-4:

'By addressing classical and neo-Latin works with which Milton's poems appear to engage, Haan has pursued something unattempted yet. Her erudite and engaging commentary on the Poemata is the most extensive and impressive that I have encountered in any edition ... Haan's discussion of Milton's Poemata - including the Testimonia, the one Italian and four Latin encomia by the poet's acquaintances published in 1645 and 1673 - is remarkably detailed and well-researched. In these sections, readers learn, for example, how Milton's Epitaphium Damonis borrows from both classical writers (Theocritus, Moschus) and contemporary models (Castiglione, Zanchi) while transcending all of them through a pattern of resurrection motifs. Or, readers can discover affinities between Milton's lament on the death of the Bishop of Ely and a poem by the Italian humanist Hieronymo Aleander, Jr., or learn about the connections between Milton's Elegia Quinta and George Buchanan's Maiae Calendae ... The Shorter Poems is a scholarly achievement of the highest order.'

Noam Reisner, Review of English Studies 65 (2014), 744-5:
‘Haan shines with her Neo-Latinist expertise by offering a vivid separate introduction to the Latin poems, which sets up Milton’s poemata specifically within the Neo-Latin contexts of the seventeenth century, thereby dispelling any remaining view of these poems as juvenilia (a view which results from reading the poems chronologically). … The present volume will instantly establish itself as the definitive resource for any reader interested in Milton’s shorter poems, and it is scarcely imaginable that it will ever be eclipsed or be in need of replacing. Its contribution is important in all areas, especially in providing for the first time in a single volume truly valuable documents which can teach us a lot more about Milton’s poetic development than simply reading the poems in chronological sequence. But perhaps, this edition’s greatest achievement is the way in which it succeeds in giving Milton’s Latin poems the pride of place they have long deserved as fully integral to Milton’s complete poetic imagination. Haan’s specific achievement in this regard is less in updating the translations than in providing a different context through which to look at the Latin poems themselves. Haan’s detailed commentaries set the Latin poems in a completely fresh light which looks beyond the obvious classical references and allusions, noted by Carey and many other editors, to Milton’s complex engagement with the Neo-Latin literary culture of his time. It is this aspect of the volume, more than anything else, which vindicates its essentialness.'

Caregiving reduces mortality risk for most caregivers: a census-based record linkage study

Importance Countries with advanced welfare systems are increasingly relying on the input of informal caregivers and there are growing concerns for their mental and physical wellbeing. However, the evidence about the relationship between caregiving and mortality risk is less clear.

Methods A census-based record linkage study with mortality follow-up of thirty-three months. A total of 1,122,779 individuals including 183,842 caregivers, of whom 28.2% (51,927) were providing fifty or more hours caregiving per week.

Results Over thirty-three months of follow-up a total of 29,335 deaths occurred, with 2,443 of these to caregivers. Mortality risk for caregivers was lower than for non-caregivers (HR= 0.72: 95%CI=0.69, 0.75 in the fully adjusted model), and the lower risk was evident even for those providing fifty or more hours of caregiving per week (adjusted Hazard Ratio=0.77: 95%CI=0.71, 0.83 and 0.76: 95%CI=0.69, 0.83 for men and women respectively). There was no evidence that this relationship varied by either age or marital status. Even amongst people with chronic health problems such as poor mental health, caregivers had lower mortality risk than non-caregivers. Caregiving is associated with reduced mortality risk for most causes - for example, the risk of death from Ischaemic Heart Disease for caregivers providing fifty or more hours was 27% and 31% lower for men and for women respectively compared to non-caregivers (HR=0.73: 95%CI=0.60, 0.88 and HR=0.69: 95%CI=0.51, 0.92).

Conclusions This large population-based study confirms that for the majority of caregivers the beneficial effects of caregiving in terms of short-term mortality risk appear to outweigh any negative effects, even amongst people with significant health problems. These results underscore the need for a reappraisal of how caregiving is perceived.


Keywords: caregiving, carers, mortality, longitudinal follow-up.
marital status. Even amongst people with chronic health problems such as poor mental health, caregivers had lower mortality risk than non-caregivers. Caregiving is associated with reduced mortality risk for most causes - for example, the risk of death from Ischaemic Heart Disease for caregivers providing fifty or more hours was 27% and 31% lower for men and for women respectively compared to non-caregivers (HR=0.73: 95%CI=0.60, 0.88 and HR=0.69: 95%CI=0.51, 0.92).

Conclusions This large population-based study confirms that for the majority of caregivers the beneficial effects of caregiving in terms of short-term mortality risk appear to outweigh any negative effects, even amongst people with significant health problems. These results underscore the need for a reappraisal of how caregiving is perceived.

Understanding Complete Oxidation of Methane on Spinel Oxides at Molecular Level

It is crucial to develop a catalyst made of earth-abundant elements highly active for a complete oxidation of methane at a relatively low temperature. NiCo₂O₄ consisting of earth-abundant elements which can completely oxidize methane in the temperature range of 350-550 °C. Being a cost-effective catalyst, NiCo₂O₄ exhibits activity higher than precious-metal-based catalysts. Here we report that the higher catalytic activity at the relatively low temperature results from the integration of nickel cations, cobalt cations and surface lattice oxygen atoms/oxygen vacancies at the atomic scale. In situ studies of complete oxidation of methane on NiCo₂O₄ and theoretical simulations show that methane dissociates to methyl on nickel cations and then couple with surface lattice oxygen atoms to form -CH₃O with a following dehydrogenation to -CH₂O; a following oxidative dehydrogenation forms CHO; CHO is transformed to product molecules through two different sub-pathways including dehydrogenation of OCHO and CO oxidation.

Autosomal dominant retinitis pigmentosa:linkage to rhodopsin and evidence for genetic heterogeneity

Retinitis pigmentosa (RP) is the most prevalent human retinopathy of genetic origin. Chromosomal locations for X-linked RP and autosomal dominant RP genes have recently been established. Multipoint analyses with ADRP and seven markers on the long arm of chromosome 3 demonstrate that the gene for rhodopsin, the pigment of the rod photoreceptors, cosegregates with the disease locus with a maximum lod score of approximately 19, implicating rhodopsin as a causative gene. Recent studies have indicated the presence of a point mutation at codon 23 in exon 1 of rhodopsin which results in the substitution of histidine for the highly conserved amino acid proline, suggesting that this mutation is a cause of rhodopsin-linked ADRP. This mutation is not present in the Irish pedigree in which ADRP has been mapped close to rhodopsin. Another mutation in the rhodopsin gene or in a gene closely linked to rhodopsin may be involved. Moreover, the gene in a second ADRP pedigree, with Type II late onset ADRP, does not segregate with chromosome 3q markers, indicating that nonallelic as well as perhaps allelic genetic heterogeneity exists in the autosomal dominant form of this disease.

Epidermolysis bullosa:evidence for linkage to genetic markers on chromosome 1 in a family with the autosomal dominant simplex form

DNA from members of a three-generation pedigree of Irish origin, displaying an autosomal dominant simplex form of epidermolysis bullosa of the epidermolytic, simplex, or Koebner variety (EBS2), was analyzed for linkage with a set of markers derived from the long arm of chromosome 1. Two-point analysis revealed positive lod scores for five of these markers, AT3 (Z = 2.107, theta = 0), APOA2 (Z = 1.939, theta = 0.15), D1S66 (Z = 1.204, theta = 0), D1S13 (Z = 1.026, theta = 0.15), and D1S65 (Z = 0.329, theta = 0.15). Multilocus analysis, incorporating the markers D1S19, D1S16, D1S13, APOA2, D1S66, AT3, and D1S65, resulted in a lod score of 3 maximizing at AT3. These data strongly support previous tentative indications of linkage between EBS2 and genetic markers on the long arm of chromosome 1.

EGF61 polymorphism predicts complete pathologic response to cetuximab-based chemoradiation independent of KRAS status in locally advanced rectal cancer patients

BACKGROUND: Cetuximab has shown significant clinical activity in metastatic colon cancer. However, cetuximab-containing neoadjuvant chemoradiation has not been shown to improve tumor response in locally advanced rectal cancer patients in recent phase I/II trials. We evaluated functional germline polymorphisms of genes involved in epidermal growth factor receptor pathway, angiogenesis, antibody-dependent cell-mediated cytotoxicity, DNA repair, and drug metabolism, for their potential role as molecular predictors for clinical outcome in locally advanced rectal cancer patients treated with preoperative cetuximab-based chemoradiation.

METHODS: 130 patients (74 men and 56 women) with locally advanced rectal cancer (4 with stage II, 109 with stage III, and 15 with stage IV, 2 unknown) who were enrolled in phase I/II clinical trials treated with cetuximab-based chemoradiation in European cancer centers were included. Genomic DNA was extracted from formalin-fixed paraffin-embedded tumor samples and genotyping was done by using PCR-RFLP assays. Fisher's exact test was used to examine associations between polymorphisms and complete pathologic response (pCR) that was determined by a modified Dworak classification system (grade III vs. grade IV: complete response).

RESULTS: Patients with the epidermal growth factor (EGF) 61 G/G genotype had pCR of 45% (5/11), compared with 21% (11/53) in patients heterozygous, and 2% (1/54) in patients homozygous for the A/A allele (P < 0.001). In addition, this association between EGF 61 G allele and pCR remained significant (P = 0.019) in the 59 patients with wild-type KRAS.

CONCLUSION: This study suggested EGF A+61G polymorphism to be a predictive marker for pCR, independent of KRAS mutation status, to cetuximab-based neoadjuvant chemoradiation of patients with locally advanced rectal cancer.