Restorative justice conferencing for reducing recidivism in young offenders (aged 7 to 21)

Background
Restorative justice is “a process whereby parties with a stake in a specific offence resolve collectively how to deal with the aftermath of the offence and its implications for the future” (Marshall 2003). Despite the increasing use of restorative justice programmes as an alternative to court proceedings, no systematic review has been undertaken of the available evidence on the effectiveness of these programmes with young offenders. Recidivism in young offenders is a particularly worrying problem, as recent surveys have indicated
the frequency of re-offences for young offenders has ranged from 40.2% in 2000 to 37.8% in 2007 (Ministry of Justice 2009)

Objectives
To evaluate the effects of restorative justice conferencing programmes for reducing recidivism in young offenders.

Search methods
We searched the following databases up to May 2012: CENTRAL, 2012 Issue 5, MEDLINE (1978 to current), Bibliography of Nordic Criminology (1999 to current), Index to Theses (1716 to current), PsycINFO (1887 to current), Social Sciences Citation Index (1970 to current), Sociological Abstracts (1952 to current), Social Care Online (1985 to current), Restorative Justice Online (1975 to current), Scopus (1823 to current), Science Direct (1823 to current), LILACS (1982 to current), ERIC (1966 to current), Restorative Justice Online (4May 2012),WorldCat (9May 2012), ClinicalTrials.gov (19May 2012) and ICTRP (19May 2012). ASSIA,National Criminal Justice Reference Service and Social Services Abstracts were searched up to May 2011. Relevant bibliographies, conference programmes and journals were also searched.

Selection criteria
Randomised controlled trials (RCTs) or quasi-RCTs of restorative justice conferencing versus management as usual, in young offenders.

Data collection and analysis
Two authors independently assessed the risk of bias of included trials and extracted the data. Where necessary, original investigators were contacted to obtain missing information.

Main results
Four trials including a total of 1447 young offenders were included in the review. Results failed to find a significant effect for restorative justice conferencing over normal court procedures for any of the main analyses, including number re-arrested (odds ratio (OR) 1.00, 95% confidence interval (CI) 0.59 to 1.71; P = 0.99), monthly rate of reoffending (standardised mean difference (SMD) -0.06, 95% CI -0.28 to 0.16; P = 0.61), young person’s remorse following conference (OR 1.73, 95% CI 0.97 to 3.10; P = 0.06), young person’s recognition of wrongdoing following conference (OR 1.97, 95% CI 0.81 to 4.80; P = 0.14), young person’s self-perception following conference (OR 0.95, 95% CI 0.55 to 1.63; P = 0.85), young person’s satisfaction following conference (OR 0.42, 95% CI 0.04 to 4.07; P = 0.45) and victim’s satisfaction following conference (OR 4.05, 95%CI 0.56 to 29.04; P = 0.16). A small number of sensitivity analyses did indicate significant effects, although all are to be interpreted with caution.

Authors’ conclusions
There is currently a lack of high quality evidence regarding the effectiveness of restorative justice conferencing for young offenders. Caution is urged in interpreting the results of this review considering the small number of included studies, subsequent low power and high risk of bias. The effects may potentially be more evident for victims than offenders. The need for further research in this area is highlighted.

Stereotactic radiosurgery for arteriovenous malformations, Part 3: outcome predictors and risks after repeat radiosurgery:outcome predictors and risks after repeat radiosurgery

The object of this study was to evaluate the outcomes and risks of repeat stereotactic radiosurgery (SRS) for incompletely obliterated cerebral arteriovenous malformations (AVMs).

Diastereoselective 1,3-dipolar cycloaddition of pyrylium ylides with chiral enamides

Chiral enamides5f-i were found to react with pyrylium ylides to give cycloadducts 6d-i in good yields with an excellent level of stereoselectivity. The chiral auxiliary was successfully removed on hydrogenolysis of compound 6f in continuous flow (H-Cube) resulting in the first asymmetric synthesis of complex amine 8.

Predicting IQ of biologically "at risk" children from age 3 to school entry:sensitivity and specificity of the Stanford-Binet Intelligence Scale IV

Predictive validity of the Stanford-Binet Intelligence Scale Fourth Edition (S-B IV) from age 3 years to ages 4-5 years was evaluated with biologically "at risk" children without major sensory or motor impairments (n = 236). Using the standard scoring, children with full scale IQ <or = 84 on the Wechsler Preschool and Primary Scale of Intelligence at age 4-5 years were poorly identified (sensitivity 54%) from the composite S-B IV score at age 3. However, sensitivity improved greatly to 78% by including as a predictor the number of subtests the child was actually able to perform at age 3 years. Measures from the Home Screening Questionnaire and ratings of mother-child interaction further improved sensitivity to 83%. The standard method for calculating the composite score on the S-B IV excludes subtests with a raw score of 0, which overestimates cognitive functioning in young biologically high risk children. Accuracy of early identification was improved significantly by considering the number of subtests the child did not perform at age 3 years.

Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia

Prior evidence has supported the existence of multiple susceptibility genes for schizophrenia. Multipoint linkage analysis of the 270 Irish high-density pedigrees that we have studied, as well as results from several other samples, suggest that at least one such gene is located in region 6p24-21. In the present study, family-based association analysis of 36 simple sequence-length-polymorphism markers and of 17 SNP markers implicated two regions, separated by approximately 7 Mb. The first region, and the focus of this report, is 6p22.3. In this region, single-nucleotide polymorphisms within the 140-kb gene DTNBP1 (dystrobrevin-binding protein 1, or dysbindin) are strongly associated with schizophrenia. Uncorrected, empirical P values produced by the program TRANSMIT were significant (P

The persistent activity of Jupiter-family comets at 3-7 AU

We present an analysis of comet activity based on the Spitzer Space Telescope component of the Survey of the Ensemble Physical Properties of Cometary Nuclei. We show that the survey is well suited to measuring the activity of Jupiter-family comets at 3-7 AU from the Sun. Dust was detected in 33 of 89 targets (37 ± 6%), and we conclude that 21 comets (24 ± 5%) have morphologies that suggest ongoing or recent cometary activity. Our dust detections are sensitivity limited, therefore our measured activity rate is necessarily a lower limit. All comets with small perihelion distances (q <1.8 AU) are inactive in our survey, and the active comets in our sample are strongly biased to post-perihelion epochs. We introduce the quantity ɛfρ, intended to be a thermal emission counterpart to the often reported Afρ, and find that the comets with large perihelion distances likely have greater dust production rates than other comets in our survey at 3-7 AU from the Sun, indicating a bias in the discovered Jupiter-family comet population. By examining the orbital history of our survey sample, we suggest that comets perturbed to smaller perihelion distances in the past 150 yr are more likely to be active, but more study on this effect is needed.

Cytokine and C-reactive protein profiles induced by porcine circovirus type 2 experimental infection in 3-week-old piglets

The purpose of this study was to determine serum profiles of cytokines at a protein level and Creactive protein (CRP) during the development of postweaning multisystemic wasting syndrome (PMWS) in experimentally inoculated pigs. Levels of serum IFN-alpha, IL-6, IL-10, and CRP were examined for a 35-day period in 10 piglets experimentally infected with PCV2 at 3 weeks of age. Four of the infected piglets developed severe PMWS at 14 to 21 days post-infection (d.p.i.) and died prior to termination of the experiment. The remaining six PCV2-infected piglets experienced transient fever, but did not display overt clinical signs of PMWS and were considered as subclinically infected. A bioassay was used to detect IL-6 and ELISAs were used to detect IFN-alpha, IL-10, and CRP. There were no significant differences in cytokine or CRP expression from 0 to 7 d.p.i. between the PMWS-affected and the subclinically infected piglets. Levels of IL-10 and CRP were elevated from 10 and 14 d.p.i. respectively in the PMWS-affected piglets compared to the subclinically infected piglets. There were no significant differences in IFN-alpha and IL-6 expression between the PMWS-affected piglets and the subclinically infected piglets. The present study shows that elevated levels of serum CRP and IL-10 were associated with PCV2-infected piglets that subsequently developed severe PMWS. This may help to provide further insight into the immunoaetiogenesis of this syndrome.

Genomic lesions associated with a different clinical outcome in diffuse large B-Cell lymphoma treated with R-CHOP-21

Despite recent therapeutic improvements, the clinical course of diffuse large B-cell lymphoma (DLBCL) still differs considerably among patients. We conducted this retrospective multi-centre study to evaluate the impact of genomic aberrations detected using a high-density genome wide-single nucleotide polymorphism-based array on clinical outcome in a population of DLBCL patients treated with R-CHOP-21 (rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone repeated every 21_d). 166 DNA samples were analysed using the GeneChip Human Mapping 250K NspI. Genomic anomalies were analysed regarding their impact on the clinical course of 124 patients treated with R-CHOP-21. Unsupervised clustering was performed to identify genetically related subgroups of patients with different clinical outcomes. Twenty recurrent genetic lesions showed an impact on the clinical course. Loss of genomic material at 8p23.1 showed the strongest statistical significance and was associated with additional aberrations, such as 17p- and 15q-. Unsupervised clustering identified five DLBCL clusters with distinct genetic profiles, clinical characteristics and outcomes. Genetic features and clusters, associated with a different outcome in patients treated with R-CHOP, have been identified by arrayCGH.

New insights into sequence variation in the IGS region of 21 cyathostomin species and the implication for molecular identification

Cyathostomins comprise a group of 50 species of parasitic nematodes that infect equids. Ribosomal DNA sequences, in particular the intergenic spacer (IGS) region, have been utilized via several methodologies to identify pre-parasitic stages of the commonest species that affect horses. These methods rely on the availability of accurate sequence information for each species, as well as detailed knowledge of the levels of intra- and inter-specific variation. Here, the IGS DNA region was amplified and sequenced from 10 cyathostomin species for which sequence was not previously available. Also, additional IGS DNA sequences were generated from individual worms of 8 species already studied. Comparative analysis of these sequences revealed a greater range of intra-specific variation than previously reported (up to 23%); whilst the level of inter-specific variation (3-62%) was similar to that identified in earlier studies. The reverse line blot (RLB) method has been used to exploit the cyathostomin IGS DNA region for species identification. Here, we report validation of novel and existing DNA probes for identification of cyathostomins using this method and highlight their application in differentiating life-cycle stages such as third-stage larvae that cannot be identified to species by morphological means.

Ataluren for the treatment of nonsense-mutation cystic fibrosis: a randomised, double-blind, placebo-controlled phase 3 trial

Background: Ataluren was developed to restore functional protein production in genetic disorders caused by nonsense mutations, which are the cause of cystic fibrosis in 10% of patients. This trial was designed to assess the efficacy and safety of ataluren in patients with nonsense-mutation cystic fibrosis. 

Methods: This randomised, double-blind, placebo-controlled, phase 3 study enrolled patients from 36 sites in 11 countries in North America and Europe. Eligible patients with nonsense-mutation cystic fibrosis (aged ≥6 years; abnormal nasal potential difference; sweat chloride >40 mmol/L; forced expiratory volume in 1 s [FEV₁] ≥40% and ≤90%) were randomly assigned by interactive response technology to receive oral ataluren (10 mg/kg in morning, 10 mg/kg midday, and 20 mg/kg in evening) or matching placebo for 48 weeks. Randomisation used a block size of four, stratified by age, chronic inhaled antibiotic use, and percent-predicted FEV₁. The primary endpoint was relative change in percent-predicted FEV₁ from baseline to week 48, analysed in all patients with a post-baseline spirometry measurement. This study is registered with ClinicalTrials.gov, number NCT00803205. 

Findings: Between Sept 8, 2009, and Nov 30, 2010, 238 patients were randomly assigned, of whom 116 in each treatment group had a valid post-baseline spirometry measurement. Relative change from baseline in percent-predicted FEV₁ did not differ significantly between ataluren and placebo at week 48 (-2·5% vs -5·5%; difference 3·0% [95% CI -0·8 to 6·3]; p=0·12). The number of pulmonary exacerbations did not differ significantly between treatment groups (rate ratio 0·77 [95% CI 0·57-1·05]; p=0·0992). However, post-hoc analysis of the subgroup of patients not using chronic inhaled tobramycin showed a 5·7% difference (95% CI 1·5-10·1) in relative change from baseline in percent-predicted FEV₁ between the ataluren and placebo groups at week 48 (-0·7% [-4·0 to 2·1] vs -6·4% [-9·8 to -3·7]; nominal p=0·0082), and fewer pulmonary exacerbations in the ataluern group (1·42 events [0·9-1·9] vs 2·18 events [1·6-2·7]; rate ratio 0·60 [0·42-0·86]; nominal p=0·0061). Safety profiles were generally similar for ataluren and placebo, except for the occurrence of increased creatinine concentrations (ie, acute kidney injury), which occurred in 18 (15%) of 118 patients in the ataluren group compared with one (<1%) of 120 patients in the placebo group. No life-threatening adverse events or deaths were reported in either group. I

nterpretation: Although ataluren did not improve lung function in the overall population of nonsense-mutation cystic fibrosis patients who received this treatment, it might be beneficial for patients not taking chronic inhaled tobramycin. 

Funding: PTC Therapeutics, Cystic Fibrosis Foundation, US Food and Drug Administration's Office of Orphan Products Development, and the National Institutes of Health. 

The novel pyrrolo-1,5-benzoxazepine, PBOX-21, potentiates the apoptotic efficacy of STI571 (imatinib mesylate) in human chronic myeloid leukaemia cells

The Bcr-Abl kinase inhibitor, STI571, is the first line treatment for chronic myeloid leukaemia (CML), but the recent emergence of STI571 resistance has led to the examination of combination therapies. In this report, we describe how a novel non-toxic G1-arresting compound, pyrrolo-1,5-benzoxazepine (PBOX)-21, potentiates the apoptotic ability of STI571 in Bcr-Abl-positive CML cells. Co-treatment of CML cells with PBOX-21 and STI571 induced more apoptosis than either drug alone in parental (K562S and LAMA84) and STI571-resistant cells lines (K562R). This potentiation of apoptosis was specific to Bcr-Abl-positive leukaemia cells with no effect observed on Bcr-Abl-negative HL-60 acute myeloid leukaemia cells. Apoptosis induced by PBOX-21/STI571 resulted in activation of caspase-8, cleavage of PARP and Bcl-2, upregulation of the pro-apoptotic protein Bim and a downregulation of Bcr-Abl. Repression of proteins involved in Bcr-Abl transformation, the anti-apoptotic proteins Mcl-1 and Bcl-(XL) was also observed. The combined lack of an early change in mitochondrial membrane potential, release of cytochrome c and cleavage of pro-caspase-9 suggests that this pathway is not involved in the initiation of apoptosis by PBOX-21/STI571. Apoptosis was significantly reduced following pre-treatment with either the general caspase inhibitor Boc-FMK or the chymotrypsin-like serine protease inhibitor TPCK, but was completely abrogated following pre-treatment with a combination of these inhibitors. This demonstrates the important role for each of these protease families in this apoptotic pathway. In conclusion, our data highlights the potential of PBOX-21 in combination with STI571 as an effective therapy against CML.