Chemical Shifts of Artificial Monomers Used to Construct Heterogeneous-Backbone Protein Mimetics in Random Coil and Folded States.

The construction of protein-sized synthetic chains that blend natural amino acids with artificial monomers to create so-called heterogeneous-backbones is a powerful approach to generate complex folds and functions from bio-inspired agents. A variety of techniques from structural biology commonly used to study natural proteins have been adapted to investigate folding in these entities. In NMR characterization of proteins, proton chemical shift is a straightforward to acquire, information-rich metric that bears directly on a variety of properties related to folding. Leveraging chemical shift to gain insight into folding requires a set of reference chemical shift values corresponding to each building block type (i.e., the 20 canonical amino acids in the case of natural proteins) in a random coil state and knowledge of systematic changes in chemical shift associated with particular folded conformations. Although well documented for natural proteins, these issues remain unexplored in the context of protein mimetics. Here, we report random coil chemical shift values for a library of artificial amino acid monomers frequently used to construct heterogeneous-backbone protein analogues as well as a spectroscopic signature associated with one monomer class, ß3-residues bearing proteinogenic side chains, adopting a helical folded conformation. Collectively, these results will facilitate the continued utilization of NMR for the study of structure and dynamics in protein-like artificial backbones.

Solid phase syntheses of peptoid like arylureido compounds and sequencing of isobars without molecular encoding.

Arylureido-backbone containing peptoid-like trimers were prepared using the one-bead-one-compound approach. Isobaric molecules were synthesized from isocyanate precursors that contain alkyl halide handles at the ortho and para-positions in the phenyl ring. After chain extension with a primary amine, the piperazine-capped molecules were sequenced using tandem mass spectrometry and successfully identified based on their fragmentation pattern without a need for internal molecular encoding.

Alcohol and its relationship to offence variables in a cohort of offenders with intellectual disability.

BACKGROUND: Alcohol use and misuse may be lower in people with intellectual disability (ID) than in the general population but may be related to offending. METHOD: Alcohol-related crime and history of alcohol use was recorded in 477 participants with ID referred to forensic ID services and related to offending. RESULTS: Level of alcohol-related crime and history of alcohol misuse was lower than in some previous studies at 5.9% and 20.8%, respectively. History of alcohol abuse was associated with alcohol-related offences and theft. Higher rates of alcohol problem history were associated with histories of a number of offences, psychiatric disturbance in adulthood, psychiatric disturbance in childhood, and experiences of childhood adversity. Most effect sizes were weak or moderate. CONCLUSIONS: The convergence of childhood adversity, psychiatric problems in childhood and adulthood, and alcohol abuse is consistent with studies that have found these as risk markers for offending.

The impact of known criminogenic factors on offenders with intellectual disability: previous findings and new results on ADHD.

BACKGROUND: Developmental and index offence variables have been implicated strongly in later criminal behaviour and service pathways and this paper investigated attention deficit hyperactivity disorder (ADHD) which, with conduct disorder, has emerged from previous studies on offenders. ADHD and conduct disorder are over-represented among criminal populations when compared to the general population. The present authors reviewed the extent to which ADHD affected the presentation of offenders with intellectual disability. METHOD: Information related to index behaviour, history of problem behaviours, childhood adversity and psychiatric diagnoses was recorded in 477 referrals to forensic intellectual disability services. Comparisons were made between those with a previous diagnosis of ADHD and those without. RESULTS: The ADHD group showed higher proportions of physical aggression, substance use, previous problems including aggression, sexual offences and property offences, birth problems and abuse in childhood. Effect sizes were small. CONCLUSION: Attention deficit hyperactivity disorder with conduct disorder is associated with a greater degree and history of problematic behaviour in offenders with intellectual disability.

Pathways through services for offenders with intellectual disability: a one- and two-year follow-up study.

The pathways through services for offenders with intellectual disability were reviewed. Participants were 197 offenders with intellectual disability accepted into three types of community and three types of secure forensic intellectual disability services. They were first compared with 280 participants referred but not accepted into services and were then followed-up for 2 years to review pathways through services. Those accepted into services had a higher charge rate than did those who were referred (46% and 25%, respectively). The greatest diversity in pathway was seen in participants in community forensic intellectual disability and inpatient services. Individuals in secure settings showed the least diversity over time, and, similarly, a relatively high percentage of those accepted into generic community services remained in these services.

Referrals into services for offenders with intellectual disabilities: variables predicting community or secure provision.

BACKGROUND: There is a need for research to promote an understanding among service developers on why people with intellectual disabilities (ID) are referred to offender services in order for them to receive appropriate assessment and treatment. Previous studies investigating referrals into forensic ID services have concentrated on referral sources and administrative variables such as legal status. AIMS: To construct a predictive model for choice of service referral based on a comprehensive range of information about the clientele. METHOD: We conducted a case record study of 336 people referred to community services and 141 to secure provision. We gathered information on referral source, demographics, diagnosis, index behaviour, prior problem behaviours and history of abuse. RESULTS: Comparisons revealed 19 candidate variables which were then entered into multivariate logistic regression. The resulting model retained six variables: community living at time of referral, physical aggression, being charged, referral from tertiary health care, diverse problem behaviour and IQ < 50, which correctly predicted the referral pathway for 85.7% of cases. CONCLUSIONS: An index act of physical aggression and a history of diversity of problem behaviours as predictors against the likelihood of community service referral suggest that professionals have similar concerns about people with ID as they do about their more average offending peers; however, the more severe levels of ID mitigated in favour of community referral, regardless. Offenders with ID tend to be referred within levels of service rather than between them, for example, form tertiary services into generic community services.

Profiling executive dysfunction in adults with autism and comorbid learning disability.

Executive dysfunction is thought to be primary to autism. We examined differences in executive function between 20 adults with autism and learning disability and 23 individuals with learning disabilities outside the autistic spectrum. All participants were matched for chronological age and full-scale IQ, and were given a battery of tasks assessing fluency, planning, set-shifting, inhibition and working memory. Analyses of the individual tasks revealed very few significant differences between the two groups. However, analyses of composite scores derived for each executive domain revealed that the group with autism showed impaired performance on the working memory and planning tests. Together, these two measures were sufficient to classify participants into their diagnostic groups significantly better than would be expected by chance (75% of the autism group; 65% of the control group). Executive impairments were neither universal nor exclusive to the autism group, and we suggest that an alternative cognitive theory may better explain the cognitive profile we found.

Risk assessment in offenders with intellectual disability: a comparison across three levels of security.

In mainstream offender samples, several risk assessments have been evaluated for predictive validity. This study extends this work to male offenders with intellectual disabilities. Participants from high-, medium-, and low-security settings, as well as community settings, were compared on a range of risk assessments. The Violence Risk Appraisal Guide, HCR-20-Historical Scale, the Risk Matrix 2000-C (combined risk), and the Emotional Problems Scales-Internalising discriminated between groups, with participants from high security having higher scores than those in medium security, who had higher scores than those in the community. The Violence Risk Appraisal Guide, all HCR-20 scales, the Short Dynamic Risk Scale, and the Emotional Problems Scales (Internalising and Externalising) showed significant areas under the curve for the prediction of violence. The Static-99 showed a significant area under the curve for the prediction of sexual incidents. The discussion reviews the value of these various scales to intellectual disability services.

Internal consistency and factor structure of personality disorders in a forensic intellectual disability sample.

BACKGROUND: The publication of the DSM-III (American Psychiatric Association (APA), 1980) prompted a significant increase in interest and research on personality disorder (PD), and the concept has subsequently been incorporated into mental health legislation in the developed world. Despite this, such research on people with intellectual disability (ID) has been sporadic, with widely varying results. The present study addresses a number of criticisms directed at previous research. METHOD: DSM-IV (APA, 2000) diagnoses of PD were made on 164 participants with ID on the basis of four independent sources of classification. RESULTS: Reliability data for each PD was acceptable and alpha was .74 or above, with the exception of schizotypal PD (.63). Exploratory and confirmatory factor analyses were conducted, with the former revealing a 4-factor solution accounting for 58.9% of the variance, and a 2-factor solution accounting for 37.2% of the variance emerging for the latter. The factors were orthogonal, and we called the first factor "avoidant/rumination/inhibited" and the second factor "acting out". DISCUSSION: We review these findings in relation to previous research on PD and alternative frameworks for the understanding of personality. We hypothesise consistencies between these findings and previous work on personality and ID. A number of drawbacks to the research are discussed, including a caution on the pejorative nature of a diagnosis of PD in an already devalued population.

Presentation of depression in autism and Asperger syndrome: a review.

Depression is common in autism and Asperger syndrome, but despite this, there has been little research into this issue. This review considers the current literature on the prevalence, presentation, treatment and assessment of depression in autism and Asperger syndrome. There are diagnostic difficulties when considering depression in autism and Asperger syndrome, as the characteristics of these disorders, such as social withdrawal and appetite and sleep disturbance, are also core symptoms of depression. Impaired verbal and non-verbal communication can mask the symptoms of depression. Symptoms associated with autism and Asperger syndrome such as obsessionality and self-injury may be increased during an episode of depression. There is a clear need to develop specific tools both for diagnostic purposes and for measurement of depression in autism and Asperger syndrome in order to help alleviate the distress caused by this treatable illness.

A comparison of offenders with intellectual disability across three levels of security.

BACKGROUND: A number of authors have described, with disparate results, the prevalence of people with intellectual disability and their characteristics, in a range of offender cohorts defined by service use. These have included high security, a range of criminal justice services and community services. There is a need for research comparing cohorts of offenders with intellectual disabilities across different settings. AIM AND HYPOTHESIS: To conduct such a comparison and test the hypothesis that severity of characteristics measured will be highest in highest levels of residential security. METHOD: A clinical-record-based comparison a offenders with intellectual disability in high security (n = 73), medium/low security (n = 70), and a community service (n = 69). RESULTS: Groups were similar in age and tested IQ levels. Early psychiatric service contact had been more likely in the lower security groups. In line with the hypothesis, more complex presentations, in particular comorbid personality disorder, was more likely in the highest security group. Both fatal and non-fatal interpersonal violence convictions were significantly related to group, with more in the high security group sustaining a conviction both at the index offence and prior to that. Over 50% of all groups had at least one conviction for a sexual offence. A regression model accounting for 78% of the variance was made up largely of disposal variables (Mental Health Act status and probation) and indications of antisocial traits (criminal damage, lifetime conviction for murder and ICD-10 personality disorder classification). CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The authors show that context of sampling affects most relationships between intellectual disability (ID) and offending when the methods for measuring ID are held constant. The results also present several questions on the relationship between risk, services available in an area and referral to higher security.

Young adults with learning disabilities: a study of psychosocial functioning at transition to adult services.

A study of the psychosocial functioning of young adults with a history of learning disability (LD) in childhood is reported. The design was a non-clinic community follow-up investigation of a cohort of children who had received special education, the sample frame for which was a birth-period cohort survey. Participants were 149 young adults (89 males and 60 females derived from a survey of the 33,800 children born in the Cambridge Health District between 1967 and 1973) at the stage of transition to adult services (age 18-22y), whose measured IQ scores in childhood were <80, and who had received special education during school years. Most of the young adults were living at home (n=108) and many were in full-time employment (independent employment n=41, sheltered employment n=20), this survey having been carried out in an area of high employment. A strong correlation was found between the child IQ score and subsequent adult Vineland Scale Score. Greater efforts should be made to detect and assess LD and its attendant problems in children in order to plan future care and transition to adulthood, especially for those with more severe disabilities.

Autism and learning disability.

In this article a short overview is given of the relationship between autism and learning disability. Autism exists with any level of intelligence, but many individuals with autism suffer also from learning disability. Although both disorders show overlap in some behaviours they are different in many aspects. Are they distinct syndromes which influence each other, or do they belong to a broad spectrum of a condition?

Attention deficit hyperactivity disorder: review of ADHD in learning disability: the Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation[DC-LD] criteria for diagnosis.

BACKGROUND: Attention deficit hyperactivity disorder [ADHD)]is believed to be common among people with learning disabilities. Classification systems in current use have presented diagnostic difficulties in this area, when used for people with learning disability (particularly adults). METHODS: A literature search using electronic databases was undertaken, and journals were hand-searched for articles relevant to the diagnosis of mental disorders in adults with intellectual disabilities. RESULTS: There is preliminary evidence that ADHD is more common in this population than among the non-learning-disabled population, and indeed that rates of hyperactivity increase with increasing severity of learning disability. There are also associations between ADHD and certain causal syndromes of learning disability. CONCLUSION: While available evidence suggests that ADHD may be common among children and adults with learning disabilities, research has been hindered by deficits in currently used diagnostic classification systems. With the recent development of criteria for the diagnosis of ADHD in learning-disabled adults, and the publication of these in Diagnostic Criteria for Learning Disabilities/Mental Retardation[DC-LD] there is scope for an increase in the level of interest in the study of ADHD among adults with learning disabilities.

The classification of problem behaviour in Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation (DC-LD).

BACKGROUND: Problem behaviour is common among adults with learning disabilities, often to an extent that it impacts upon the functioning and social inclusion of the individual, and of the individual's family and immediate social network. METHODS/RESULTS: However, most approaches to the classification and diagnosis of psychiatric disorder among people with learning disability do not deal with problem behaviour as a diagnosis. The recent innovation of the Diagnostic Criteria for Psychiatric Disorders for Use with Adults with Learning Disabilities/Mental Retardation (DC-LD) includes diagnostic criteria for problem behaviour. The background and the thinking behind these criteria are reviewed. CONCLUSIONS: It is proposed that the adoption of such criteria offers the possibility of improved services for the individuals concerned, with resultant improvements in their adaptation and social inclusion.

Absence of auditory 'global interference' in autism.

There has been considerable recent interest in the cognitive style of individuals with Autism Spectrum Disorder (ASD). One theory, that of weak central coherence, concerns an inability to combine stimulus details into a coherent whole. Here we test this theory in the case of sound patterns, using a new definition of the details (local structure) and the coherent whole (global structure). Thirteen individuals with a diagnosis of autism or Asperger's syndrome and 15 control participants were administered auditory tests, where they were required to match local pitch direction changes between two auditory sequences. When the other local features of the sequence pairs were altered (the actual pitches and relative time points of pitch direction change), the control participants obtained lower scores compared with when these details were left unchanged. This can be attributed to interference from the global structure, defined as the combination of the local auditory details. In contrast, the participants with ASD did not obtain lower scores in the presence of such mismatches. This was attributed to the absence of interference from an auditory coherent whole. The results are consistent with the presence of abnormal interactions between local and global auditory perception in ASD.

Hyperactivity and conduct disorder: exploring origins.

OBJECTIVES: This paper explores the relationship of hyperactivity (HA), conduct disorder (CD) and combined hyperactivity and conduct disorder (HACD) with certain environmental and biological stresses and vulnerabilities. METHOD: It is based upon a large epidemiological database from the North of England. RESULTS: The findings suggest that CD is uncommon and strongly related to environmental stresses. This is true to a lesser extent of HACD. While both CD and HACD were related to family adversity and adverse styles of parental discipline, subtly different patterns of associations are also evident. In particular, CD is linked with poverty, parental violence and contact with child care social agencies. These findings are consistent with the hypothesis that HA contributes to a pattern of confrontation and punishment associated, in some cases, with the emergence of a more complex combination disturbance. However, CD occurs against a background of family conflict and poor child-care. CONCLUSIONS: Most apparent cases of conduct disorder are in fact hybrid conditions including symptoms of HA and CD. True CD should be diagnosed not only by positive symptomatology but also by the absence of hyperactivity symptoms.