Controlling chlorination versus cyclosulfonation of cis-diols using ionic liquid solvents

Diol reactivity can be manipulated in ionic liquids to selectively give chlorinated or cyclic sulfite/sulfate products depending on the ionic liquid used and the presence or absence of base. In comparison with reactions in dichloromethane, the ionic liquid mediated reactions show greatly improved yields and product stability.

Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age

The genetic contribution to the variation in human lifespan is approximately 25%.  Despite the large number of identified disease-susceptibility loci, it is not known which loci influence population mortality.  We performed a genome-wide association meta-analysis of 7729 long-lived individuals of European descent (≥ 85 years) and 16121 younger controls (< 65 years) followed by replication in an additional set of 13060 long-lived individuals and 61156 controls. In addition, we performed a subset analysis in cases ≥ 90 years. We observed genome-wide significant association with longevity, as reflected by survival to ages beyond 90 years, at a novel locus, rs2149954, on chromosome 5q33.3 (OR = 1.10, P =1.74 x 10-8). We also confirmed association of rs4420638 on chromosome 19q13.32 (OR = 0.72, P = 3.40 x 10-36), representing the TOMM40/APOE/APOC1 locus. In a prospective meta-analysis (n = 34103) the minor allele of rs2149954 (T) on chromosome 5q33.3 associates with increased survival (HR = 0.95, P = 0.003). This allele has previously been reported to associate with low blood pressure in middle age. Interestingly, the minor allele (T) associates with decreased cardiovascular mortality risk, independent of blood pressure. We report on the first GWAS-identified longevity locus on chromosome 5q33.3 influencing survival in the general European population. The minor allele of this locus associates with low blood pressure in middle age, although the contribution of this allele to survival may be less dependent on blood pressure. Hence, the pleiotropic mechanisms by which this intragenic variation contributes to lifespan regulation have to be elucidated.

Prevalence of potentially inappropriate prescribing and prescribing omissions in Irish adults: findings from the Irish LongituDinal Study on Ageing (TILDA)

Purpose: We sought to estimate the prevalence of potentially inappropriate prescriptions (PIP) and potential prescribing omissions (PPOs) using a subset of the STOPP/START criteria in a population based sample of Irish adults aged ≥65 years using data from The Irish LongituDinal Study on Ageing (TILDA).

Methods: A subset of 26 PIP indicators and 10 PPO indicators from the STOPP/START criteria were applied to the TILDA dataset. PIP/PPO prevalence according to individual STOPP/START criteria and the overall prevalence of PIP/PPO were estimated. The relationship between PIP and PPOs and polypharmacy, age, gender and multimorbidity was examined using logistic regression.

Results: The overall prevalence of PIP in the study population (n = 3,454) was 14.6 %. The most common examples of PIP identified were NSAID with moderate-severe hypertension (200 participants; 5.8 %) and aspirin with no history of coronary, cerebral, or peripheral vascular symptoms or occlusive event (112 participants; 3.2 %). The overall prevalence of PPOs was 30 % (n = 1,035). The most frequent PPO was antihypertensive therapy where systolic blood pressure consistently >160 mmHg (n = 341, 9.9 %), There was a significant association between PIP and PPO and polypharmacy when adjusting for age, sex and multimorbidity (adjusted OR 2.62, 95 % CI 2.05–3.33 for PIP and adjusted OR 1.46, 95 % CI 1.23–1.75 for prescribing omissions).

Conclusion: Our findings indicate prescribing omissions are twice as prevalent as PIP in the elderly using a subset of the STOPP/START criteria as an explicit process measure of potentially inappropriate prescribing and prescribing omissions. Polypharmacy was independently associated with both PPO and PIP. Application of such screening tools to prescribing decisions may reduce unnecessary medication, related adverse events, healthcare utilisation and cost.

Intakes of dietary folate and other B vitamins are associated with risks of esophageal adenocarcinoma, Barrett's esophagus, and reflux esophagitis

Folate is implicated in carcinogenesis via effects on DNA synthesis, repair, and methylation. Efficient folate metabolism requires other B vitamins and is adversely affected by smoking and alcohol. Esophageal adenocarcinoma (EAC) may develop through a process involving inflammation [reflux esophagitis (RE)] leading to metaplasia [Barrett’s esophagus (BE)] and carcinoma. Within a population-based, case-control study, we investigated associations between dietary folate and related factors and risks of EAC, BE, and RE. EAC and BE cases had histologically confirmed disease; RE cases had endoscopically visible inflammation. Controls, age-sex frequency matched to EAC cases, were selected through population and general practice registers. Participants underwent structured interviews and completed food-frequency questionnaires. Multivariate ORs and 95% CIs were computed using logistic regression. A total of 256 controls and 223 EAC, 220 BE, and 219 RE cases participated. EAC risk decreased with increasing folate intake (OR highest vs. lowest = 0.56; 95% CI: 0.31, 1.00; P-trend < 0.01). Similar trends were found for BE (P-trend < 0.01) and RE (P-trend = 0.01). Vitamin B-6 intake was significantly inversely related to risks of all 3 lesions. Riboflavin intake was inversely associated with RE. Vitamin B-12 intake was positively associated with EAC. For EAC, there was a borderline significant interaction between folate intake and smoking (P-interaction = 0.053); compared with nonsmokers with high (≥median) folate intake, current smokers with low intakes (<median) had an 8-fold increased risk (OR: 8.15; 95% CI: 3.61, 18.40). The same group had increased BE risk (OR: 2.93; 95% CI: 1.24, 6.92; P-interaction = 0.12). Folate and other dietary methyl-group factors are implicated in the etiology of EAC and its precursors.

Young people, crime and justice in Northern Ireland

Many children and young people in conflict with the law in Northern Ireland have experienced living in poverty, truancy or exclusion from school, limited educational attainment, neglect or abuse within their families, placement in alternative care, drug or alcohol misuse, physical and mental ill-health. However, their lives are also affected by the legacy and particular circumstances of a society in transition from conflict. In addition to historical under-investment in services for children and their families, this includes discriminatory policing alongside informal regulation by ‘paramilitaries’ or members of ‘the community’ and community-based restorative justice schemes as an alternative way of dealing with low-level crime and ‘anti-social’ behaviour.

Following a Criminal Justice Review, the 2002 Justice (Northern Ireland) Act affirmed that the principal aim of the youth justice system is to protect the public by preventing offending by children’. Youth justice initiatives therefore encompass a range of responses: early intervention to prevent offending and the application of civil Anti-Social Behaviour Orders, diversionary measures (including community-based restorative justice schemes), non-custodial disposals for those found guilty of offences, and custodial sentences. While ‘policy transfer’ prevailed during periods of ‘direct rule’ from Westminster, the punitive responses to ‘sub-criminal’ and ‘anti-social’ behaviour introduced by the 1998 Crime and Disorder Act in England and Wales were resisted or not implemented in the same way in Northern Ireland.

This Chapter will critically analyse the debates informing recent developments, noting key issues raised by the 2011 review of youth justice initiated as a priority following the devolution of justice and policing to the Northern Ireland Assembly. It will focus on promotion and protection of the rights of children and young people in conflict with the law.

Evaluating conditions for transboundary marine spatial planning: Challenges and opportunities on the island of Ireland

Transboundary cooperation is viewed as an essential element of Marine Spatial Planning (MSP). While much of the MSP literature focuses on the need for, and benefits of, transboundary MSP, this paper explores the political and institutional factors that may facilitate the effective transition to such an approach. Drawing on transboundary planning theory and practice, key contextual factors that are likely to expedite the transition to transboundary MSP are reviewed. These include: policy convergence in neighbouring jurisdictions; prior experience of transboundary planning; and good working relations amongst key actors. Based on this review, an assessment of the conditions for transboundary MSP in the adjoining waters of Northern Ireland and the Republic of Ireland is undertaken. A number of recommendations are then advanced for transboundary MSP on the island of Ireland, including, the need to address the role of formal transboundary institutions and the lack of an agreed legal maritime boundary. The paper concludes with some commentary on the political realities of implementing transboundary MSP.

Sexual Abuse in Institutional Contexts

This chapter adopts a cross-national comparative perspective on institutional child sexual abuse. It seeks first to provide a critical overview of a range of high profile inquiries and official reviews into allegations of institutional child abuse and the dominant transnational themes arising from them. It also seeks to highlight the dynamics of what I have previously termed 'institutional grooming' (McAlinden, 2006) and the features of the organisational environment which both facilitate institutional child sexual abuse and help mask its discovery or disclosure. In so doing, the analysis examines the tension between what others have termed 'preferential' or 'situational' sexual offending – that is whether offenders deliberately set out to gain employment which affords access to children or whether the motivation to sexually offend only emerges after they become ensconced in an institutional environment. Finally, the article concludes by offering some suggestions for combatting institutional grooming and sexual abuse.

Polymorphism in Sulfadimidine/4-Aminosalicylic Acid Cocrystals: Solid-State Characterization and Physicochemical Properties

Polymorphism of crystalline drugs is a common phenomenon. However, the number of reported polymorphic cocrystals is very limited. In this work, the synthesis and solid-state characterization of a polymorphic cocrystal composed of sulfadimidine (SD) and 4-aminosalicylic acid (4-ASA) is reported for the first time. By liquid-assisted milling, the SD:4-ASA 1:1 form I cocrystal, the structure of which has been previously reported, was formed. By spray drying, a new polymorphic form (form II) of the SD:4-ASA 1:1 cocrystal was discovered which could also be obtained by solvent evaporation from ethanol and acetone. Structure determination of the form II cocrystal was calculated using high-resolution X-ray powder diffraction. The solubility of the SD:4-ASA 1:1 cocrystal was dependent on the pH and predicted by a model established for a two amphoteric component cocrystal. The form I cocrystal was found to be thermodynamically more stable in aqueous solution than form II, which showed transformation to form I. Dissolution studies revealed that the dissolution rate of SD from both cocrystals was enhanced when compared with a physical equimolar mixture and pure SD.

Geographical differences in first acquisition of Pseudomonas aeruginosa in cystic fibrosis

RATIONALE: Risk of infection with Pseudomonas aeruginosa in cystic fibrosis (CF) may be associated with environmental factors.

OBJECTIVES: To determine whether residential location is associated with risk of first acquisition of P. aeruginosa.

METHODS: We performed bronchoalveolar lavage and upper airway cultures in children newly diagnosed with CF to identify infection with P. aeruginosa during infancy and early childhood. Children were assessed according to their residence in a regional or metropolitan area. Multilocus sequence typing was used to determine P. aeruginosa genotype. An environmental questionnaire was also administered.

MEASUREMENTS AND MAIN RESULTS: A total of 105 of 120 (87.5%) infants diagnosed with CF were included in this study. Diagnosis in 65 infants (61.9%) followed newborn screening at mean age of 4.6 weeks. Sixty subjects (57.1%) were homozygous ΔF508, and 47 (44.8%) were female. Fifty-five (52.3%) infants were regional, of whom 26 (47.3%), compared with 9 of 50 (18.0%) metropolitan children, acquired infection with P. aeruginosa (odds ratio, 4.084; 95% confidence interval, 1.55-11.30). Age at acquisition was similar (regional: median, 2.31 yr; range, 0.27-5.96 yr; metropolitan: median, 3.10 yr, range, 0.89-3.70 yr). Strain typing identified P. aeruginosa genotypes often encountered in different ecological settings and little evidence of cross-infection. Ninety questionnaires (85.7%) were completed. Those who acquired P. aeruginosa were more likely to be living in a household that used water sprinkler systems (P = 0.032), but no differences were identified to explain increased risk of acquisition of P. aeruginosa in regional children.

CONCLUSIONS: Geographical difference in residence of children with CF was associated with increased risk of first acquisition of P. aeruginosa, usually with strains associated with the environment rather than with cross-infection.

Risk, Regulation and the Reintegration of Sexual Offenders

Media reporting of and public concern about sexual offending, particularly relating to children, affects and reflects political, policy and organisational responses to those convicted of such crimes. The development of regulatory policies on sexual offending has taken place within a highly emotive and overtly politicized public and policy discourse. This chapter charts the various ways in which the risks imagined or posed by sexual offenders have been conceptualised within public discourses and regulated and managed under the legislative and organisational ‘risk paradigm.’ Ultimately, it argues that risk-based responses to sexual offending are at best uncertain in their effects and at worst counterproductive, in that they often reduce the potential for successful reintegration. In seeking to look ‘beyond risk’, the chapter also explores the usefulness of restorative and related practices in supporting sex offender reintegration aimed at the primary and secondary levels of harm prevention.

Restorative Justice and Sex Offending

This essay examines the origins and uses of restorative justice with sexual offending and the contemporary challenges and controversies surrounding this. It charts the range of ad hoc initiatives which have sought to apply a restorative form of intervention with violent or sexual offending from first time and ‘acquaintance’ rape as well as young sexual abusers to high risk sexual offenders in the form of circles of support and accountability. Such schemes are often presented as a counter to the failings of retributive forms of justice and are premised on Braithwaite’s (1989) notion of ‘reintegrative shaming’ that seek to reintegrate offenders into the community. Critics of restorative justice traditionally put forward a number of core objectives when restorative justice is applied to serious forms of offending such as sexual offending. The essay also sets out and seeks to counter these principal challenges and how they may be overcome. For the most part, however, restorative justice has failed to reach its potential as a fully fledged sentencing rationale in being applied as a mainstream response to a wide range of offending including that at the higher end of the spectrum. The essay also seeks to examine barriers to restorative justice within contemporary penal policy and to highlight some of the most controversial applications of the restorative paradigm including those related to clergy sexual abuse. It concludes by offering some thoughts on the future of restorative justice as a mainstream responses to serious forms of offending.