A multi-centre study of adults with learning disabilities referred to services for antisocial or offending behaviour: demographic, individual, offending and service characteristics

This study was carried out as part of a larger study commissioned by the UK Department of Health to investigate the service pathways for offenders with learning disabilities (LD). The study covered three health regions in the UK and included 477 people with LD referred to services because of antisocial or offending behaviour during a 12-month period. Data were collected concerning demographic, individual, offending behaviour and service characteristics. The findings of the study are broadly consistent with contemporary research concerning this population, particularly in relation to the nature and frequency of offending, history of offending, psychopathology, age and gender distribution. However, very few of those referred had any form of structured care plan, despite having significant offending histories, and this may have compromised early identification of their needs and communication between the health, social and other services involved

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

Germline genetic variation and predicting immune checkpoint inhibitor induced toxicity

Immune checkpoint inhibitor (ICI) therapy has revolutionised the treatment of various cancer types. ICIs reinstate T-cell function to elicit an anti-cancer immune response. The resulting immune response can however have off-target effects which manifest as autoimmune type serious immune-related adverse events (irAE) in ~10–55% of patients treated. It is currently challenging to predict both who will experience irAEs and to what severity. Identification of patients at high risk of serious irAE would revolutionise patient care. While the pathogenesis driving irAE development is still unclear, host genetic factors are proposed to be key determinants of these events. This review presents current evidence supporting the role of the host genome in determining risk of irAE. We summarise the spectrum and timing of irAEs following treatment with ICIs and describe currently reported germline genetic variation associated with expression of immuno-modulatory factors within the cancer immunity cycle, development of autoimmune disease and irAE occurrence. We propose that germline genetic determinants of host immune function and autoimmune diseases could also explain risk of irAE development. We also endorse genome-wide association studies of patients being treated with ICIs to identify genetic variants that can be used in polygenic risk scores to predict risk of irAE

Exploring the origins of the power-law properties of energy landscapes: An egg-box model

Multidimensional potential energy landscapes (PELs) have a Gaussian distribution for the energies of the minima, but at the same time the distribution of the hyperareas for the basins of attraction surrounding the minima follows a power-law. To explore how both these features can simultaneously be true, we introduce an ``egg-box'' model. In these model landscapes, the Gaussian energy distribution is used as a starting point and we examine whether a power-law basin area distribution can arise as a natural consequence through the swallowing up of higher-energy minima by larger low-energy basins when the variance of this Gaussian is increased sufficiently. Although the basin area distribution is substantially broadened by this process,it is insufficient to generate power-laws, highlighting the role played by the inhomogeneous distribution of basins in configuration space for actual PELs.Comment: 7 pages, 8 figure

Plasma protein biomarkers for depression and schizophrenia by multi analyte profiling of case-control collections.

Despite significant research efforts aimed at understanding the neurobiological underpinnings of psychiatric disorders, the diagnosis and the evaluation of treatment of these disorders are still based solely on relatively subjective assessment of symptoms. Therefore, biological markers which could improve the current classification of psychiatry disorders, and in perspective stratify patients on a biological basis into more homogeneous clinically distinct subgroups, are highly needed. In order to identify novel candidate biological markers for major depression and schizophrenia, we have applied a focused proteomic approach using plasma samples from a large case-control collection. Patients were diagnosed according to DSM criteria using structured interviews and a number of additional clinical variables and demographic information were assessed. Plasma samples from 245 depressed patients, 229 schizophrenic patients and 254 controls were submitted to multi analyte profiling allowing the evaluation of up to 79 proteins, including a series of cytokines, chemokines and neurotrophins previously suggested to be involved in the pathophysiology of depression and schizophrenia. Univariate data analysis showed more significant p-values than would be expected by chance and highlighted several proteins belonging to pathways or mechanisms previously suspected to be involved in the pathophysiology of major depression or schizophrenia, such as insulin and MMP-9 for depression, and BDNF, EGF and a number of chemokines for schizophrenia. Multivariate analysis was carried out to improve the differentiation of cases from controls and identify the most informative panel of markers. The results illustrate the potential of plasma biomarker profiling for psychiatric disorders, when conducted in large collections. The study highlighted a set of analytes as candidate biomarker signatures for depression and schizophrenia, warranting further investigation in independent collections

Pathways into services for offenders with intellectual disabilities : childhood experience, diagnostic information and offence variables

The patterns and pathways into intellectual disability (ID) offender services were studied through case file review for 477 participants referred in one calendar year to community generic, community forensic, and low, medium, and maximum secure services. Data were gathered on referral source, demographic information, index behavior, prior problem behaviors, diagnostic information, and abuse or deprivation. Community referrers tended to refer to community services and secure service referrers to secure services. Physical and verbal violence were the most frequent index behaviors, whereas contact sexual offenses were more prominent in maximum security. Age at first incident varied with security, with the youngest in maximum secure services. Attention-deficit/hyperactivity disorder or conduct disorder was the most frequently recorded diagnosis, and severe deprivation was the most frequent adverse developmental experience. Fire starting, theft, and road traffic offenses did not feature prominently. Generic community services accepted a number of referrals with forensic-type behavior and had higher proportions of both women and people with moderate or severe ID

A scoping review of nurse-led randomised controlled trials

Background: Nurses comprise the largest portion of the healthcare workforce worldwide. However, nurse representation in the leadership of clinical research and research funding is largely unknown. The Australasian Nursing and Midwifery Clinical Trials Network was established to provide a coordinated network, focussed on building research capacity in nursing and midwifery. To support this work, this scoping review of nurse-led randomised controlled trials was conducted to summarise research activity, as well as highlight future research directions, gaps and resources. Midwife-led trials will be reported elsewhere. Aim: To quantify number, type and quality of nurse-led randomised controlled trials registered between 2000–2021. Design: A scoping review of RCTs. Data Sources: Medline, Emcare and Scopus were searched from 2000 to August 2021. ANZCTR, NHMRC, MRFF and HRC (NZ) registries were searched from inception to July 2021. Review Methods: This review was informed by the JBI scoping review framework using the PRISMA-ScR. Results: Our search yielded 186 nurse-led publications and 279 registered randomised controlled trials. Multiple trials had the same nurse leaders. There were more registrations than publications. Publications were predominantly of high methodological quality; however, there was a reliance on active controls and blinding low. Trial registrations indicate that universities and hospital/healthcare organisations were the major sources of funding, while publications indicate that Governments and the National Health and Medical Research Council were the main funding bodies. Conclusion: A small number of high-quality, large-scale, nationally funded randomised controlled trials were identified, with a larger number of locally funded small trials. There was a disparity between the number of registered trials and those published. Additional infrastructure, funding and career frameworks are needed to enable nurses to design, conduct and publish clinical trials that inform the health system and improve health outcomes. Relevance to Clinical Practice: Research initiated and led by nurses has the potential to improve the health and well-being of individuals and communities, and current nurse-led research is of high methodological quality; however, there were very few nurse-led RCTs, conducted by a small pool of nurse researchers. This gap highlights the need for support in the design, conduct and publishing of nurse-led RCTs. Patient or Public Contribution: This is a scoping review; therefore, patient or public contribution is not applicable

Evaluation of Education Maintenance Allowance Pilots : Leeds and London first year evidence

This report refers to findings from the first year of the EMA pilot in Leeds and London, which was September 1999 to August 2000

MDSC targeting with Gemtuzumab ozogamicin restores T cell immunity and immunotherapy against cancers

Background: Targeting of MDSCs is a major clinical challenge in the era of immunotherapy. Antibodies which deplete MDSCs in murine models can reactivate T cell responses. In humans such approaches have not developed due to difficulties in identifying targets amenable to clinical translation. Methods: RNA-sequencing of M-MDSCs and G-MDSCs from cancer patients was undertaken. Flow cytometry and immunohistochemistry of blood and tumours determined MDSC CD33 expression. MDSCs were treated with Gemtuzumab ozogamicin and internalisation kinetics, and cell death mechanisms determined by flow cytometry, confocal microscopy and electron microscopy. Effects on T cell proliferation and CAR-T cell anti-tumour cytotoxicity were identified in the presence of Gemtuzumab ozogamicin. Findings: RNA-sequencing of human M-MDSCs and G-MDSCs identified transcriptomic differences, but that CD33 is a common surface marker. Flow cytometry indicated CD33 expression is higher on M-MDSCs, and CD33+ MDSCs are found in the blood and tumours regardless of cancer subtype. Treatment of human MDSCs leads to Gemtuzumab ozogamicin internalisation, increased p-ATM, and cell death; restoring T cell proliferation. Anti-GD2-/mesothelin-/EGFRvIII-CAR-T cell activity is enhanced in combination with the anti-MDSC effects of Gemtuzumab ozogamicin. Interpretation: The study identifies that M-MDSCs and G-MDSCs are transcriptomically different but CD33 is a therapeutic target on peripheral and infiltrating MDSCs across cancer subtypes. The immunotoxin Gemtuzumab ozogamicin can deplete MDSCs providing a translational approach to reactivate T cell and CAR-T cell responses against multiple cancers. In the rare conditions of HLH/MAS gemtuzumab ozogamicin provides a novel anti-myeloid strategy. Fund: This work was supported by Cancer Research UK, CCLG, Treating Children with Cancer, and the alumni and donors to the University of Birmingham. (c) 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)