Is Camouflaging Autistic Traits Associated with Suicidal Thoughts and Behaviours? Expanding the Interpersonal Psychological Theory of Suicide in an Undergraduate Student Sample.

The current study explored whether people who camouflage autistic traits are more likely to experience thwarted belongingness and suicidality, as predicted by the Interpersonal Psychological Theory of Suicide (IPTS). 160 undergraduate students (86.9% female, 18-23 years) completed a cross-sectional online survey from 8th February to 30th May 2019 including self-report measures of thwarted belongingness and perceived burdensomeness, autistic traits, depression, anxiety, camouflaging autistic traits, and lifetime suicidality. Results suggest that camouflaging autistic traits is associated with increased risk of experiencing thwarted belongingness and lifetime suicidality. It is important for suicide theories such as the IPTS to include variables relevant to the broader autism phenotype, to increase applicability of models to both autistic and non-autistic people.

Measurement properties of tools used to assess suicidality in autistic and general population adults: A systematic review.

Adults diagnosed with autism are at significantly increased risk of suicidal thoughts, suicidal behaviours and dying by suicide. However, it is unclear whether any validated tools are currently available to effectively assess suicidality in autistic adults in research and clinical practice. This is crucial for understanding and preventing premature death by suicide in this vulnerable group. This two stage systematic review therefore aimed to identify tools used to assess suicidality in autistic and general population adults, evaluate these tools for their appropriateness and measurement properties, and make recommendations for appropriate selection of suicidality assessment tools in research and clinical practice. Three databases were searched (PsycInfo, Medline and Web of Knowledge). Four frequently used suicidality assessment tools were identified, and subsequently rated for quality of the evidence in support of their measurement properties using the COSMIN checklist. Despite studies having explored suicidality in autistic adults, none had utilised a validated tool. Overall, there was lack of evidence in support of suicidality risk assessments successfully predicting future suicide attempts. We recommend adaptations to current suicidality assessment tools and priorities for future research, in order to better conceptualise suicidality and its measurement in autism.

Measurement properties of tools used to assess depression in adults with and without autism spectrum conditions: A systematic review.

Depression is the most commonly experienced mental health condition in adults with autism spectrum conditions (ASC). However, it is unclear what tools are currently being used to assess depression in ASC, or whether tools need to be adapted for this group. This systematic review therefore aimed to identify tools used to assess depression in adults with and without ASC, and then evaluate these tools for their appropriateness and measurement properties. Medline, PsychINFO and Web of Knowledge were searched for studies of depression in: (a) adults with ASC, without co-morbid intellectual disability; and (b) adults from the general population without co-morbid conditions. Articles examining the measurement properties of these tools were then searched for using a methodological filter in PubMed, and the quality of the evidence was evaluated using the COSMIN checklist. Twelve articles were identified which utilized three tools to assess depression in adults with ASC, but only one article which assessed the measurement properties of one of these tools was identified and thus evaluated. Sixty-four articles were identified which utilized five tools to assess depression in general population adults, and fourteen articles had assessed the measurement properties of these tools. Overall, two tools were found to be robust in their measurement properties in the general population-the Beck Depression Inventory (BDI-II), and the patient health questionnaire (PHQ-9). Crucially only one study was identified from the COSMIN search, which showed weak evidence in support of the measurement properties of the BDI-II in an ASC sample. Implications for effective measurement of depression in ASC are discussed. Autism Res 2018, 11: 738-754. © 2018 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. LAY SUMMARY: Depression is the most common mental health problem experienced by adults with autism. However, the current study found very limited evidence regarding how useful tools developed for the general population are for adults with autism. We therefore suggest how these tools could be adapted to more effectively assess depression in adults with autism, and improve these individuals access to mental health assessment and support.

Are autistic traits associated with suicidality? A test of the interpersonal-psychological theory of suicide in a non-clinical young adult sample.

Autism spectrum conditions (ASC) has recently been associated with increased risk of suicidality. However, no studies have explored how autistic traits may interact with current models of suicidal behavior in a non-clinical population. The current study therefore explored how self-reported autistic traits interact with perceived burdensomeness and thwarted belongingness in predicting suicidal behavior, in the context of the Interpersonal-Psychological Theory of Suicide (IPTS). 163 young adults (aged 18-30 years) completed an online survey including measures of thwarted belonging and perceived burdensomeness (Interpersonal Needs Questionnaire), self-reported autistic traits (Autism Spectrum Quotient), current depression (Centre for Epidemiological Studies Depression Scale), and lifetime suicidality (Suicide Behavior Questionnaire-Revised). Results showed that burdensomeness and thwarted belonging significantly mediated the relationship between autistic traits and suicidal behavior. Both depression and autistic traits significantly predicted thwarted belonging and perceived burdensomeness. Autistic traits did not significantly moderate the relationship between suicidal behavior and thwarted belonging or perceived burdensomeness. Results suggest that the IPTS provides a useful framework for understanding the influence of autistic traits on suicidal behavior. However, the psychometric properties of these measures need be explored in those with clinically confirmed diagnosis of ASC. Autism Res 2017, 10: 1891-1904. © 2017 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. LAY SUMMARY: Recent research has shown that people with high autistic traits are more likely to attempt suicide. However, no studies have explored why. We found that people with high autistic traits were more likely to experience feelings that they do not belong in the world, are a burden on others, and depression, which may increase their likelihood of attempting suicide. These results suggest that promoting inclusion and independence in those with high autistic traits could help prevent people attempting suicide.

STAT4-associated natural killer cell tolerance following liver transplantation.

OBJECTIVE: Natural killer (NK) cells are important mediators of liver inflammation in chronic liver disease. The aim of this study was to investigate why liver transplants (LTs) are not rejected by NK cells in the absence of human leukocyte antigen (HLA) matching, and to identify a tolerogenic NK cell phenotype. DESIGN: Phenotypic and functional analyses on NK cells from 54 LT recipients were performed, and comparisons made with healthy controls. Further investigation was performed using gene expression analysis and donor:recipient HLA typing. RESULTS: NK cells from non-HCV LT recipients were hypofunctional, with reduced expression of NKp46 (p<0.05) and NKp30 (p<0.001), reduced cytotoxicity (p<0.001) and interferon (IFN)-γ secretion (p<0.025). There was no segregation of this effect with HLA-C, and these functional changes were not observed in individuals with HCV. Microarray and RT-qPCR analysis demonstrated downregulation of STAT4 in NK cells from LT recipients (p<0.0001). Changes in the expression levels of the transcription factors Helios (p=0.06) and Hobit (p=0.07), which control NKp46 and IFNγ expression, respectively, were also detected. Hypofunctionality of NK cells was associated with impaired STAT4 phosphorylation and downregulation of the STAT4 target microRNA-155. Conversely in HCV-LT NK cell tolerance was reversed, consistent with the more aggressive outcome of LT for HCV. CONCLUSIONS: LT is associated with transcriptional and functional changes in NK cells, resulting in reduced activation. NK cell tolerance occurs upstream of major histocompatibility complex (MHC) class I mediated education, and is associated with deficient STAT4 phosphorylation. STAT4 therefore represents a potential therapeutic target to induce NK cell tolerance in liver disease.

Expressive visual text-to-speech as an assistive technology for individuals with autism spectrum conditions.

Adults with Autism Spectrum Conditions (ASC) experience marked difficulties in recognising the emotions of others and responding appropriately. The clinical characteristics of ASC mean that face to face or group interventions may not be appropriate for this clinical group. This article explores the potential of a new interactive technology, converting text to emotionally expressive speech, to improve emotion processing ability and attention to faces in adults with ASC. We demonstrate a method for generating a near-videorealistic avatar (XpressiveTalk), which can produce a video of a face uttering inputted text, in a large variety of emotional tones. We then demonstrate that general population adults can correctly recognize the emotions portrayed by XpressiveTalk. Adults with ASC are significantly less accurate than controls, but still above chance levels for inferring emotions from XpressiveTalk. Both groups are significantly more accurate when inferring sad emotions from XpressiveTalk compared to the original actress, and rate these expressions as significantly more preferred and realistic. The potential applications for XpressiveTalk as an assistive technology for adults with ASC is discussed.

Recognition of GC base pairs by triplex forming oligonucleotides containing nucleosides derived from 2-aminopyridine.

We have attempted to alleviate the pH dependency of triplex recognition of guanine by using intermolecular triplexes containing 2-amino-5-(2-deoxy-d-ribofuranosyl)pyridine (AP) as an analogue of 2'-deoxycytidine (dC). We find that for the beta-anomer of AP, the complex between (AP)6T6and the target site G6A6*T6C6is stable, generating a clear DNase I footprint at oligonucleotide concentrations as low as 0.25 microM at pH 5.0, in contrast to 50 microM C6T6which has no effect on the cleavage pattern. This complex is still stable at pH 6.5 producing a footprint with 1 microM oligonucleotide. Oligonucleotides containing the alpha-anomer of AP are much less effective than the beta-anomer, though in some instances they are more stable than the unmodified oligonucleotides. The results of molecular dynamics studies on a range of AP-containing triplexes has rationalized the observed stability behaviour in terms of hydrogen-bonding behaviour.

DNA sequence specificity of a naphthylquinoline triple helix-binding ligand.

We have examined the effect of a naphthylquinoline triplex-binding ligand on the formation of intermolecular triplexes on DNA fragments containing the target sites A6G6xC6T6 and G6A6xT6C6. The ligand enhances the binding of T6C2, but not T2C6, to A6G6xC6T6 suggesting that it has a greater effect on TxAT than C+xGC triplets. The complex with T6C2 is only stable below pH 6.0, confirming the requirement for protonation of the third strand cytosines. Antiparallel triplexes with GT-containing oligonucleotides are also stabilised by the ligand. The complex between G5T5 and A6G6xC6T6 is stabilised by lower ligand concentrations than that between T5G5 and G6A6xC6T6. The ligand does not promote the interaction with GT-containing oligonucleotides which have been designed to bind in a parallel orientation. Although the formation of antiparallel triplexes is pH independent, we find that the ligand has a greater stabilising effect at lower pH, suggesting that the active species is protonated. The ligand does not promote the binding of antiparallel GA-containing oligonucleotides at pH 7.5 but induces the interaction between A5G5 and G6A6xT6C6 at pH 5.5. Ethidium bromide does not promote the formation of any of these triplexes and destabilises the interaction of acridine-linked pyrimidine-containing third strands with these target sites.

Effect of a triplex-binding ligand on parallel and antiparallel DNA triple helices using short unmodified and acridine-linked oligonucleotides.

We have used DNase I footprinting to investigate the effect of a triplex-binding ligand on the formation of intermolecular DNA triple helices at target sites that have been cloned into longer DNA fragments. In the presence of a triplex-binding ligand (N-[2-(dimethylamino)ethyl]-2-(2-naphthyl)quinolin-4-ylamine ), the concentrations of T5C5 and C5T5 required to generate DNase I footprints at the target sites A6G6.C6T6 and G6A6.T6C6, respectively, are reduced by at least 100-fold. Complexes with the acridine-linked oligonucleotides Acr-T5C5 and Acr-C5T5 are stabilized to a much lesser extent and produce footprints at concentrations similar to those of the unmodified oligonucleotides in the presence of the ligand. The stabilizing effects of acridine modification or the addition of a triplex-binding ligand are not additive. The position and length of the footprints produced by Acr-T5C5 and T5C5 at the target sequence A6G6.C6T6 are unaffected by the ligand. In contrast, footprints at the target site G6A6.T6C6 appear 3-4 bases shorter in the presence of the ligand, when viewed from the pyrimidine strand, and 1-2 bases longer on the purine strand. These results are explained by suggesting that the compound binds at T.AT triplets and prevents the transmission of any DNA structural changes into the flanking duplex. The compound has a smaller stabilizing effect on short antiparallel triplexes consisting of G.GC and T.AT triplets. Binding of Acr-G5T5 to A6G6.C6T6 is enhanced slightly by the compound, which increases the apparent footprinting site, probably by preventing fraying at the 3'-end of the third strand. The compound does not promote the binding of G5T5 to A6G6.C6T6 or that of Acr-T5G5 and T5G5 to G6A6.T6C6.

Interaction of mithramycin with isolated GC and CG sites.

We have studied the interaction of the GC-specific, minor groove-binding ligand, mithramycin, with cloned DNA inserts containing isolated GC and CG sites flanked by regions of (AT)n and An.Tn using DNase I and hydroxyl radical footprinting. We find that mithramycin binds to GC better than CG and that AGCT is a better site than TGCA. Sites flanked by (AT)n appear to be bound better than those surrounded by An.Tn. Although no footprints are produced at T9GCA9 and T15CGA15, DNase I cleavage is enhanced within the GC sites suggesting that there is some interaction with the ligand. Mithramycin also alters the DNase I cleavage of (GA)n.(CT)n.

Kinetic chromatographic sequential addition immunoassays using protein A affinity chromatography.

A new type of chromatographic immunoassay based on sequential addition is described. On a protein A column, the antibody, the sample containing the antigen, and then a known amount of antigen are sequentially injected. This assay is designed to shorten analysis times and reduce complexity of dual-column chromatographic immunoassays, circumvent desorption buffer interferences common to affinity chromatography, and eliminate the need for tagged molecules. This new technique is named kinetic immunochromatography sequential addition (KICQA). Because of its kinetic nature, flow rate will have a large effect on KICQA, and the impact of changing flow rate is studied extensively. By use of various amounts of antibody, the dynamic range of KICQA is shown to be selectable over 2.5 orders of magnitude. Finally, KICQA was used to determine transferrin and albumin in human serum. Both analytes show good agreement with their respective reference methods, and an albumin assay was performed in under 1 min.

Megestrol acetate in the treatment of advanced post-menopausal breast cancer.

The effect of megestrol acetate 160 mg daily was studied in 49 previously treated post-menopausal patients with advanced carcinoma of the breast. An overall response of 31% was obtained with 1 complete and 14 partial remissions, chiefly in soft tissue and bone. The median duration of response was in excess of 10 months. Toxicity was minimal and the only notable side effect was mild weight gain without fluid retention. Megestrol acetate is safe and well tolerated, with useful activity in the palliation of advanced breast cancer.