Circulating and synovial antibody profiling of juvenile arthritis patients by nucleic acid programmable protein arrays.

Introduction Juvenile idiopathic arthritis (JIA) is a heterogeneous disease characterized by chronic joint inflammation of unknown cause in children. JIA is an autoimmune disease and small numbers of auto-antibodies have been reported in JIA patients. The identification of antibody markers could improve the existing clinical management of patients. Methods A pilot study was performed on the application of a high-throughput platform, nucleic acid programmable protein arrays (NAPPA), to assess the levels of antibodies present in the systemic circulation and synovial joint of a small cohort of juvenile arthritis patients. Plasma and synovial fluid from ten JIA patients was screened for antibodies against 768 proteins on NAPPA. Results Quantitative reproducibility of NAPPA was demonstrated with >0.95 intra- and inter- array correlations. A strong correlation was also observed for the levels of antibodies between plasma and synovial fluid across the study cohort (r=0.96). Differences in the levels of 18 antibodies were revealed between sample types across all patients. Patients were segregated into two clinical subtypes with distinct antibody signatures by unsupervised hierarchical cluster analysis. Conclusions NAPPA provides a high-throughput quantitatively reproducible platform to screen for disease specific autoantibodies at the proteome level on a microscope slide. The strong correlation between the circulating antibody levels and those of the inflamed joint represents a novel finding and provides confidence to use plasma for discovery of autoantibodies in JIA, thus circumventing the challenges associated with joint aspiration. We expect that autoantibody profiling of JIA patients on NAPPA could yield antibody markers that can act as criteria to stratify patients, predict outcomes and understand disease etiology at the molecular level.

Notes from Some Small Countries: A Study of the 'New Punitiveness' in Ireland, Scotland and New Zealand

In recent years there has been a remarkable surge of interest in the concept of punitiveness in theoretical criminology. Accounts serve to emphasise rupture over continuity, drawing attention to the increased focus on managerialism, risk and expressive penal policies in countries such as England and the US. Criticisms of these accounts have drawn attention to the weak empirical base for such assertions and the continued relevance of local cultural, historical and political conditions in mediating the effect of more punitive trends. In light of the relative neglect of smaller jurisdictions in this literature it was decided to locate these debates in three small common law jurisdictions, namely, Ireland, Scotland and New Zealand over the period 1976-2006 with a view to assessing the empirical evidence for penal change. This was done using a broader definition of punitiveness than normally employed incorporating indices relating to the ‘front end’ (eg police powers) as well as the ‘back end’ (eg prison and probation) of the criminal justice system. Data were collected on the three case studies using a multi-method approach involving examination of extensive quantitative data, interviews with key criminal justice stakeholders and documentary analysis. The data provide some support for the ‘new punitiveness’ thesis in these countries through a pattern of increased legislative activity aimed at controlling violent and sexual offenders and significant increases in the lengths of sentences imposed. However, analysis of qualitative data and a larger number of variables reveals distinctly different patterns of punitiveness over the thirty year period in the three countries. It is argued that the study holds important lessons for comparative criminology into the ‘new punitiveness’. There is a need for qualitative as well as quantitative data; for multiple rather than singular indices across a wide range of areas (juvenile justice, prison conditions, etc); and for ‘front end’ as well as ‘back end’ indices.

Second-to-Fourth Digit Ratio and Impulsivity: A Comparison between Offenders and Nonoffenders

Personality characteristics, particularly impulsive tendencies, have long been conceived as the primary culprit in delinquent behavior. One crucial question to emerge from this line of work is whether impulsivity has a biological basis. To test this possibility, 44 male offenders and 46 nonoffenders completed the Eysenck Impulsivity Questionnaire, and had their 2D:4D ratio measured. Offenders exhibited smaller right hand digit ratio measurements compared to non-offenders, but higher impulsivity scores. Both impulsivity and 2D:4D ratio measurements significantly predicted criminality (offenders vs. nonoffenders). Controlling for education level, the 2D:4D ratio measurements had remained a significant predictor of criminality, while impulsivity scores no longer predicted criminality significantly. Our data, thus, indicates that impulsivity but not 2D:4D ratio measurements relate to educational attainment. As offenders varied in their number of previous convictions and the nature of their individual crimes, we also tested for differences in 2D:4D ratio and impulsivity among offenders. Number of previous convictions did not correlate significantly with the 2D:4D ratio measurements or impulsivity scores. Our study established a link between a biological marker and impulsivity among offenders (and lack thereof among non-offenders), which emphasise the importance of studying the relationship between biological markers, impulsivity and criminal behavior.

Characteristics of offenders:The HEXACO model of personality as a framework for studying offenders' personality

What are the personality differences between individuals who commit crime and those who refrain from crime? The HEXACO model of personality combines facets of honesty and humility with those of emotionality, extraversion, conscientiousness, agreeableness, and openness to experience within a unifying framework of personality. We applied the HEXACO model to examine differences in personality between offenders and nonoffenders. Criminal offenders differed from nonoffenders on five of the six dimensions of personality proposed by the HEXACO model. Compared to nonoffenders, offenders exhibited stronger tendencies toward greed and unfairness, but were also more anxious and fearful. Conversely, the offenders scored lower than nonoffenders on a number of facets of sociability, liveliness, and social boldness. The present findings indicate that offenders may in part be characterized by increased negative emotions but decreased sociability and liveliness. The HEXACO model of personality provides a valuable tool for studying this unique and important population. © 2012 Copyright Taylor and Francis Group, LLC.

Effectiveness of Criminal Justice Liaison and Diversion Services for Offenders With Mental Disorders: A Review

Objective: The authors evaluated and synthesised the best-available evidence relating to the effectiveness of CJLD service models with respect to changes in mental health status and/or criminal recidivism.Methods: Research examining the effectiveness of CJLD services when compared to traditional Criminal Justice System (CJS) responses was reviewed and systematically appraised according to Campbell/Cochrane guidelines. Key outcomes included a reduction in offending and post-intervention changes in mental health. Results: Comprehensive searches of published and unpublished literature identified 6571 studies which varied considerably in terms of their methodological approach and overall quality. Ten studies met the inclusion criteria. The synthesised findings indicated that, when compared to traditional CJS outcomes, CJLD services appeared to be effective in terms of identifying MDOs and impacting positively on criminal justice and mental health outcomes.Conclusions: Although the evidence may be deemed to be moderate in terms of methodological rigour, overall, the findings suggest that CJLD services can be beneficial. The effectiveness of services depends upon the model of service delivery, the availability of community services and the engagement of MDOs.The successful implementation of CJLD services requires a clearer recognition of the importance of system of care principles.

Synovial membrane protein expression differs between juvenile idiopathic arthritis subtypes in early disease

Introduction: Juvenile idiopathic arthritis (JIA) is the most common rheumatological disease of childhood with a prevalence of around 1 in 1000. Without appropriate treatment it can have devastating consequences including permanent disability from joint destruction and growth deformities. Disease aetiology remains unknown. Investigation of disease pathology at the level of the synovial membrane is required if we want to begin to understand the disease at the molecular and biochemical level. The synovial membrane proteome from early disease-stage, treatment naive JIA patients was compared between polyarticular and oligoarticular subgroups.

Methods: Protein was extracted from 15 newly diagnosed, treatment naive JIA synovial membrane biopsies and separated by two dimensional fluorescent difference in-gel electrophoresis. Proteins displaying a two-fold or greater change in expression levels between the two subgroups were identified by matrix assisted laser desorption ionization-time of flight mass spectrometry with expression further verified by Western blotting and immunohistochemistry.

Results: Analysis of variance analysis (P <= 0.05) revealed 25 protein spots with a two-fold or greater difference in expression levels between polyarticular and oligoarticular patients. Hierarchical cluster analysis with Pearson ranked correlation revealed two distinctive clusters of proteins. Some of the proteins that were differentially expressed included: integrin alpha 2b (P = 0.04); fibrinogen D fragment (P =0.005); collagen type VI (P = 0.03); fibrinogen gamma chain (P = 0.05) and peroxiredoxin 2 (P = 0.02). The identified proteins are involved in a number of different processes including platelet activation and the coagulation system.

Conclusions: The data indicates distinct synovial membrane proteome profiles between JIA subgroups at an early stage in the disease process. The identified proteins also provide insight into differentially perturbed pathways which could influence pathological events at the joint level.

Offenders' Risk-Taking Attitude Inside and Outside the Prison Walls

It has long been assumed that risk taking is closely associated with criminal behavior. One reason for placing criminals behind bars-aside from punishment and protecting the public-is to prevent them from engaging in further risky criminal activities. Limited attention has been paid to whether being inside or outside prison affects offenders' risk-taking behaviors and attitudes. We compared risk-taking behaviors and attitudes in five risk domains (ethical, financial, health/safety, recreational, social) among 75 incarcerated offenders (i.e., offenders who are currently in prison) and 45 ex-offenders (i.e., offenders who have just been released from prison). Ex-offenders reported higher likelihood of engaging in risky behavior, driven largely by a willingness to take more risks in the recreational and ethical domains. Benefits attributed to risk taking as well as risk perception did not differ between incarcerated and ex-offenders, indicating that the opportunity to take risks might underlie behavioral risk intentions. Our results also indicate that risk-taking activities are better predicted by the expected benefits rather than by risk perception, aside from the health/safety domain. These results highlight the importance of studying the person and the environment and examining risk taking in a number of content domains.

Examining the introduction of legislation in Ireland to tackle juvenile anti-social behaviour

In July 2006, the Irish Parliament passed legislation aimed at tackling anti-social behaviour following a perceived increase in the problem. The new provisions are based on existing law and practice in England and Wales. However, the legislation includes a framework for dealing with juveniles that differs in a number of respects from that which exists in England and Wales. This article examines how the Irish legislation proposes to treat juveniles engaged in antisocial behaviour and contrasts this with the English approach.

The Reintegration of Sex Offenders: Barriers and Opportunities for Employment

The process of reintegration of offenders after release from prison, or during a community sentence, is a key aim of criminal justice policy. This article provides details from recent research that investigated the barriers and opportunities to employment for sex offenders. The authors describe the barriers that are faced by sex offenders and the anxieties that employers experience when employing sex offenders. The authors conclude that the approach taken by the State is less than reintegrative and serves to increase the barriers and reduce the opportunities for employment for sex offenders.

Seasonal differences in the effects of oscillatory and uni-directional flow on the growth and nitrate-uptake rates of juvenile Laminaria digitata (Phaeophyceae)

The influence of oscillatory versus unidirectional flow on the growth and nitrate-uptake rates of juvenile kelp, Laminaria digitata, was determined seasonally in experimental treatments that simulated as closely as possible natural environmental conditions. In winter, regardless of flow condition (oscillatory and unidirectional) or water velocity, no influence of water motion was observed on the growth rate of L. digitata. In summer, when ambient nitrate concentrations were low, increased water motion enhanced macroalgal growth, which is assumed to be related to an increase in the rate of supply of nutrients to the blade surface. Nitrate-uptake rates were significantly influenced by water motion and season. Lowest nitrate-uptake rates were observed for velocities <5 cm · s−1 and nitrate-uptake rates increased by 20%–50% under oscillatory motion compared to unidirectional flow at the same average speed. These data further suggested that the diffusion boundary layer played a significant role in influencing nitrate-uptake rates. However, while increased nitrate-uptake in oscillatory flow was clear, this was not reflected in growth rates and further work is required to understand the disconnection of nitrate-uptake and growth by L. digitata in oscillatory flow. The data obtained support those from related field-based studies, which suggest that in summer, when insufficient nitrogen is available in the water to saturate metabolic demand, the growth rate of kelps will be influenced by water motion restricting mass transfer of nitrogen.

RNAi dynamics in Juvenile Fasciola spp. Liver flukes reveals the persistence of gene silencing in vitro

Background: Fasciola spp. liver fluke cause pernicious disease in humans and animals. Whilst current control is unsustainable due to anthelmintic resistance, gene silencing (RNA interference, RNAi) has the potential to contribute to functional validation of new therapeutic targets. The susceptibility of juvenile Fasciola hepatica to double stranded (ds)RNA-induced RNAi has been reported. To exploit this we probe RNAi dynamics, penetrance and persistence with the aim of building a robust platform for reverse genetics in liver fluke. We describe development of standardised RNAi protocols for a commercially-available liver fluke strain (the US Pacific North West Wild Strain), validated via robust transcriptional silencing of seven virulence genes, with in-depth experimental optimisation of three: cathepsin L (FheCatL) and B (FheCatB) cysteine proteases, and a σ-class glutathione transferase (FheσGST).

Methodology/Principal Findings: Robust transcriptional silencing of targets in both F. hepatica and Fasciola gigantica juveniles is achievable following exposure to long (200–320 nt) dsRNAs or 27 nt short interfering (si)RNAs. Although juveniles are highly RNAi-susceptible, they display slower transcript and protein knockdown dynamics than those reported previously. Knockdown was detectable following as little as 4h exposure to trigger (target-dependent) and in all cases silencing persisted for ≥25 days following long dsRNA exposure. Combinatorial silencing of three targets by mixing multiple long dsRNAs was similarly efficient. Despite profound transcriptional suppression, we found a significant time-lag before the occurrence of protein suppression; FheσGST and FheCatL protein suppression were only detectable after 9 and 21 days, respectively.

Conclusions/Significance: In spite of marked variation in knockdown dynamics, we find that a transient exposure to long dsRNA or siRNA triggers robust RNAi penetrance and persistence in liver fluke NEJs supporting the development of multiple-throughput phenotypic screens for control target validation. RNAi persistence in fluke encourages in vivo studies on gene function using worms exposed to RNAi-triggers prior to 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.