A qualitative study of the transition to employment of former university students on the autism spectrum from Australia and New Zealand.

Many former university students on the autism spectrum have poor employment outcomes despite strengths, qualifications, and ability. This article presents findings from a qualitative study of 11 former university students on the spectrum (self-identified: 2 males, 7 females, 2 non-binary, 18-50+ years), and five significant others (2 mothers, 3 spouses), from Australia and New Zealand. We identified issues associated with better and poorer transition to employment experiences (poor mental health, lack of support, poor interview skills). The former students also indicated a belief that it was not the role of a university education to prepare students for employment. This belief may have influenced their discipline choices and attitude towards using career supports and university employability components. The participants who studied non-vocationally specific qualifications described more difficulty with conceptualising their transition to employment, developing an employment goal, and finding work. It was suggested that universities may need to provide comprehensive transition to employment programs that develop the 'soft skills' required for employment and offer work placements for both vocationally and non-vocationally oriented courses to help students build skills that increase their employability.

Axon-derived PACSIN1 binds to the Schwann cell survival receptor, LRP1, and transactivates TrkC to promote gliatrophic activities.

Schwann cells (SCs) undergo phenotypic transformation and then orchestrate nerve repair following PNS injury. The ligands and receptors that activate and sustain SC transformation remain incompletely understood. Proteins released by injured axons represent important candidates for activating the SC Repair Program. The low-density lipoprotein receptor-related protein-1 (LRP1) is acutely up-regulated in SCs in response to injury, activating c-Jun, and promoting SC survival. To identify novel LRP1 ligands released in PNS injury, we applied a discovery-based approach in which extracellular proteins in the injured nerve were captured using Fc-fusion proteins containing the ligand-binding motifs of LRP1 (CCR2 and CCR4). An intracellular neuron-specific protein, Protein Kinase C and Casein Kinase Substrate in Neurons (PACSIN1) was identified and validated as an LRP1 ligand. Recombinant PACSIN1 activated c-Jun and ERK1/2 in cultured SCs. Silencing Lrp1 or inhibiting the LRP1 cell-signaling co-receptor, the NMDA-R, blocked the effects of PACSIN1 on c-Jun and ERK1/2 phosphorylation. Intraneural injection of PACSIN1 into crush-injured sciatic nerves activated c-Jun in wild-type mice, but not in mice in which Lrp1 is conditionally deleted in SCs. Transcriptome profiling of SCs revealed that PACSIN1 mediates gene expression events consistent with transformation to the repair phenotype. PACSIN1 promoted SC migration and viability following the TNFα challenge. When Src family kinases were pharmacologically inhibited or the receptor tyrosine kinase, TrkC, was genetically silenced or pharmacologically inhibited, PACSIN1 failed to induce cell signaling and prevent SC death. Collectively, these studies demonstrate that PACSIN1 is a novel axon-derived LRP1 ligand that activates SC repair signaling by transactivating TrkC.

Emotion regulation in children (ERiC): A protocol for a randomised clinical trial to evaluate the clinical and cost effectiveness of Mentalization Based Treatment (MBT) vs Treatment as Usual for school-age children with mixed emotional and behavioural difficulties.

BACKGROUND: The majority of children referred to Child and Adolescent Mental Health Services (CAMHS) in the UK will present with mixed emotional and behavioural difficulties, but most mental health treatments are developed for single disorders. There is a need for research on treatments that are helpful for these mixed difficulties, especially for school-age children. Emotion Regulation (ER) difficulties present across a wide range of mental health disorders and mentalizing may help with regulation. The ability to mentalize one's own experiences and those of others plays a key role in coping with stress, regulation of emotions, and the formation of stable relationships. Mentalization Based Therapy (MBT) is a well-evidenced therapy that aims to promote mentalization, which in turn increases ER capacities, leading to decreased emotional and behavioural difficulties. The aim of this study is to test the clinical- and cost-effectiveness of MBT compared to treatment as usual for school age children with emotional and behavioural difficulties. If effective, we hope this approach can become available to the growing number of children presenting to mental health services with a mix of emotional and behavioural difficulties. MATERIALS AND METHODS: Children referred to CAMHS aged 6-12 with mixed mental health problems (emotional and behavioural) as primary problem can take part with their parent/carers. Children will be randomly allocated to receive either MBT or treatment as usual (TAU) within the CAMHS clinic they have been referred to. MBT will be 6-8 sessions offered fortnightly and can flexibly include different family members. TAU is likely to include CBT, parenting groups, and/or children's social skills groups. Parent/carers and children will be asked to complete outcome assessments (questionnaires and tasks) online at the start of treatment, mid treatment (8 weeks), end of treatment (16 weeks) and at follow up (40 weeks). TRIAL REGISTRATION: Clinical trial registration: ISRCTN 11620914.

Low-Grade Fumarate Hydratase-Deficient Renal Cell Carcinoma in a 30-Year-Old Female.

Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) is a rare and clinically aggressive RCC subtype that is commonly associated with the hereditary leiomyomatosis and renal cell carcinoma syndrome. The diagnostic hallmark of FH-deficient RCC is a high-grade microscopic appearance with prominent inclusion-like eosinophilic nucleoli and perinucleolar halos. Herein we report a case of an FH-deficient RCC in a 30-year-old female that exhibited low-grade nuclei and abundant eosinophilic cytoplasm, reminiscent of the clinically more indolent succinate dehydrogenase-deficient RCC subtype and the newly described eintity, eosinophilic, solid and cystic RCC. This case illustrates that FH-deficient RCC can have a wide spectrum of microscopic appearances, including low-grade eosinophilic RCC. In addition, it highlights that a low threshold to perform the immunohistochemical stains for FH and S-(2-succino) cysteine is warranted in RCC cases with unusual and even low-grade eosinophilic morphology.

Short report: Learning through iconic gesture in autism spectrum disorder.

BACKGROUND: Understanding and therefore recalling spoken messages, including narratives, can be challenging for children with autism. While observing gesture can benefit narrative recall in typically developing children, whether observing gesture facilitates narrative recall in children with autism is unclear. AIMS: This paper examines whether observing iconic gestures affects narrative recall in children with a diagnosis of autism. METHODS AND PROCEDURES: We first identified iconic gestures to be observed by participants in the main study. Once appropriate iconic gestures had been identified, children with autism watched one video narrative with iconic gestures and one without gestures. While watching the video narratives, children wore Tobii Pro Glasses-2 to track their eye-movements. After watching each narrative, children were asked questions about the narratives to assess recall. OUTCOMES: Iconic gestures significantly benefitted narrative recall in children with autism beyond watching no gestures, and eye-tracking results suggested gestures helped children focus on the narrator. CONCLUSIONS AND IMPLICATIONS: Through identifying appropriate iconic gestures and producing them alongside a verbal narrative, gestures may successfully enhance learning in children with autism.

How Does Participation in Formal Education or Learning for Older People Affect Wellbeing and Cognition? A Systematic Literature Review and Meta-Analysis.

Objective: To determine the effect of later-life formal education or learning on quality of life (QOL), wellbeing, mood, and cognition. Methods: A systematic literature review of interventional clinical trials and observational studies was conducted for adults aged ≥55 years who had undertaken formal education or learning programs. Outcome measures included physical activity, happiness, affective and behavioral symptoms, cognitive function, and QOL. Bias was assessed using funnel plots, Egger's test, and leave1out analysis. Results: From 32 studies identified, we showed qualitative increases in cognitive function, life satisfaction, and self-confidence associated with learning. A meta-analysis revealed a significant pooled mean difference in MMSE scores (0.40, 95% confidence intervals = [0.12, 0.67]). Although there was a low risk of publication bias there was a high risk of sampling bias. Conclusion: Participation in formal education or learning contributed to increased wellbeing, QOL, healthy cognitive function, self-dependency, and a sense of belonging in older adults.

A Structured Cognitive Intervention Pathway as a decision-support tool for non-pharmacological interventions within a dementia care service (Innovative practice).

Individual cognitive interventions for Alzheimer's disease have been shown to be beneficial and cost effective when evaluated as sole interventions. However, there is a need for a systematic, person-centric, structured approach to guide non-pharmacological intervention selection based on disease stage, symptoms, outcome assessment, and individual requirements. Our Structured Cognitive Intervention Pathway aims to facilitate the selection of first-line, or subsequent, non-pharmacological management for people with Alzheimer's disease living at home and in elderly care facilities. We discuss the Pathway's conceptual basis and evaluation of implementation as a decision-support tool within a dementia care service in China.

Management of cognitive decline in Alzheimer's disease using a non-pharmacological intervention program: A case report.

INTRODUCTION: In China, the over 60 population is estimated to grow from 12% in 2010 to 33% of the overall population by 2050. The escalation in the aging population is projected to result in an Alzheimer's disease prevalence of 27.7 million people in China by 2050 causing substantial health and economic burden. While there are some published studies on multicomponent, non-pharmacological interventions for people with dementia, we have found no published community-based approach to care that encompasses personalized selection of non-pharmacological interventions, active social participation, and dementia education. PATIENT CONCERNS: An elderly female living at home alone in urban Beijing presented with significant short-term memory impairment, episodes of confusion, difficulty with language skills, and episodes of wandering. She had become reclusive and disengaged from her previous social networks, and no longer attended any community activities or events. The patient had no significant past medical or psychiatric history. DIAGNOSIS: The patient was diagnosed with Alzheimer's disease by a local physician based on clinical features of impaired communication, disorientation, confusion, poor judgement, behavioral changes, and difficulty speaking. Depression was considered a differential diagnosis but is also both a risk factor and symptom of dementia. INTERVENTIONS: A novel, community-based, multicomponent social care program for dementia was used to facilitate implementation of non-pharmacological interventions, gradual socialization and provide supportive carer and community education. Non-pharmacological interventions included a combination of validation therapy, music therapy, art therapy, reminiscence therapy, talking therapy, reality orientation, cognitive training, smell therapy, food therapy, sensory stimulation, garden therapy, and physiotherapy. OUTCOMES: Improvements in the patient's Geriatric Depression Scale and Mini Mental State Examination scores were noted in association with increased social participation in the community. CONCLUSION: The community-based, multicomponent dementia social care program described in this case report has enabled a socially isolated patient with Alzheimer's disease to reduce her social isolation with an associated improvement in her mood and prevention of cognitive decline. Educating the community was an essential part of re-integrating the patient into the social setting. Reducing social isolation and increasing community engagement were essential to maintaining the patient's independence in her own home.

Barriers to dementia diagnosis and care in China.

In China, the ageing population and the prevalence of dementia are projected to escalate significantly by 2050 resulting in a substantial increase in health and economic burden on caregivers, healthcare facilities, healthcare providers and communities. There is no published national dementia policy or strategy in China. This case report describes significant barriers contributing to diagnostic problems and inadequate care of dementia through the case of an older female in rural China, whose condition deteriorated due to neuropsychiatric and functional symptoms of undiagnosed dementia. Intersectoral collaboration between care organisations facilitated delivery of a non-pharmacological intervention programme which was associated with improvements in the patient's functional and neuropsychiatric symptoms. The case demonstrates that recruitment and training of a wider range of health and care professionals and caregivers in a systematic approach to non-pharmacological interventions could help overcome barriers to the specialised care needs of people with dementia where resources are lacking.

Perspectives of Former Students with ASD from Australia and New Zealand on Their University Experience.

The university experience of students with ASD was explored through a qualitative study of 11 former university students and six significant others from Australia and New Zealand. A range of key issues were identified including difficulties encountered when studying, reasons for completion and non-completion, supports used, and coping strategies used by the participants. Many switched to part-time to manage their poor mental health and/or executive function and most had slow rates of progress. Also, some felt they had made poor discipline choices. The participants offered suggestions for future students and for making universities more autism friendly, and the possible need for transition and more structured study supports was identified.

Partner Perceptions of Conversations with Individuals with Autism Spectrum Disorder.

Pragmatic difficulties resulting in problems with reciprocal conversation are widely studied in individuals with autism spectrum disorder (ASD). There is some consensus on the conversation differences between individuals with autism compared to neurotypical groups and groups with other developmental delays. There is little information on whether conversation partners (neurotypical or with ASD) of individuals with ASD find these differences problematic. The results indicate that behaviors reported to be the most problematic were not necessarily behaviors commonly addressed in research. Further, some conversational capacities that have received less research focus were perceived as more problematic. Although conversation partners who had ASD themselves reported the frequency of behaviors similarly to the neurotypical group, they did not find the behaviors as problematic.

An On-Line Survey of University Students with Autism Spectrum Disorder in Australia and New Zealand: Characteristics, Support Satisfaction, and Advocacy.

An on-line survey of 102 (51 females; undergraduate and graduate) university students with ASD across Australia and New Zealand examined student characteristics and satisfaction with academic and non-academic supports. A broad range of disciplines were studied, and the participants' reported strengths included a passion for learning, strong technology skills, and creative thoughts. The participants' greatest concerns were academic requirements and mental health, including high rates of self-harm and suicidal ideation. Despite support satisfaction ratings being high, support usage was low, possibly indicating a mismatch of supports and needs, lack of awareness of available supports, and/or poor advocacy skills.

An individualised, non-pharmacological treatment strategy associated with an improvement in neuropsychiatric symptoms in a man with dementia living at home.

More than 90% of people with dementia experience neuropsychiatric symptoms which are often distressing and can result in early institutionalisation, diminished quality of life, increased frequency of emergency department visits along with stress and ill-health in caregivers. Non-pharmacological interventions are recommended as first-line treatment for neuropsychiatric symptoms, instead of medications such as atypical antipsychotics which have significant side effects. Most systematic reviews of non-pharmacological interventions for neuropsychiatric symptoms of dementia focus on patients in long-term care facilities and there are a limited number of research studies assessing the use of non-pharmacological interventions for patient's living at home. In this case report, we discuss an elderly man with dementia whose cognitive symptoms were accompanied by significant neuropsychiatric symptoms of suspicion, delusions, agitation and aggression. We describe how a programme of individualised, non-pharmacological interventions was associated with an improvement in neuropsychiatric symptoms within 3 months.

A Systematic Literature Review of Empirical Research on Postsecondary Students with Autism Spectrum Disorder.

The findings from a systematic literature review of 24 empirical studies of interventions for post-secondary students with autism spectrum disorder (ASD) are reported in this study. A diverse range of interventions were examined, many of which appeared feasible and high rates of participant satisfaction were also reported. Differing responses within and among interventions may point to the possible need for individualized supports. Few studies analyzed a specific academic support despite many students with ASD indicating they prefer these supports and that they find them useful. This may highlight the need for participant preferences to be given more consideration when designing supports. Most studies were of poor quality, however, so any conclusions are tentative. Directions for future research were discussed.

Activation of Rho Family GTPases by Small Molecules.

Ras and Ras-related small GTPases are key regulators of diverse cellular functions that impact cell growth, survival, motility, morphogenesis, and differentiation. They are important targets for studies of disease mechanisms as well as drug discovery. Here, we report the characterization of small molecule agonists of one or more of six Rho, Rab, and Ras family GTPases that were first identified through flow cytometry-based, multiplexed high-throughput screening of 200000 compounds. The activators were categorized into three distinct chemical families that are represented by three lead compounds having the highest activity. Virtual screening predicted additional compounds with potential GTPase activating properties. Secondary dose-response assays performed on compounds identified through these screens confirmed agonist activity of 43 compounds. While the lead and second most active small molecules acted as pan activators of multiple GTPase subfamilies, others showed partial selectivity for Ras and Rab proteins. The compounds did not stimulate nucleotide exchange by guanine nucleotide exchange factors and did not protect against GAP-stimulated GTP hydrolysis. The activating properties were caused by a reversible stabilization of the GTP-bound state and prolonged effector protein interactions. Notably, these compounds were active both in vitro and in cell-based assays, and small molecule-mediated changes in Rho GTPase activities were directly coupled to measurable changes in cytoskeletal rearrangements that dictate cell morphology.

Perspectives of University Students with Autism Spectrum Disorder.

Students with autism spectrum disorder (ASD) are at heightened risk of post-secondary educational failure and account for approximately 1% of students in post-secondary education. Findings from an on-line survey of students with ASD attending university in Australian are reported in this study. Respondents indicated high rates of academic and non-academic difficulties but low usage of supports. Ratings for supports were idiosyncratic, and some students indicated discomfort from using supports or disclosing their disability. Those students who delayed their disclosure accessed fewer supports and reported a poorer overall university experience. Recommendations were made including the need for better transition support and alternative strengths based approaches that use more flexible and individualised curriculum designs.

Friendship Satisfaction in Children with Autism Spectrum Disorder and Nominated Friends.

The current study examined the level of friendship satisfaction of children with autism spectrum disorder (ASD) and their nominated friends (with and without diagnosis of ASD). A total of 77 target children with ASD and friends from 49 nominated friendships participated in the study. Relatively high levels of friendship satisfaction were reported by both target children and their nominated friends with no overall difference between dyads involving typically developing friends and friends with ASD. Analysis at the individual dyad level showed a high level of agreement on the reported level of satisfaction across the target participants and their friends. Limitations and directions for future research are presented.

Cyclic AMP efflux inhibitors as potential therapeutic agents for leukemia.

Apoptotic evasion is a hallmark of cancer. We propose that some cancers may evade cell death by regulating 3'-5'-cyclic adenosine monophosphate (cAMP), which is associated with pro-apoptotic signaling. We hypothesize that leukemic cells possess mechanisms that efflux cAMP from the cytoplasm, thus protecting them from apoptosis. Accordingly, cAMP efflux inhibition should result in: cAMP accumulation, activation of cAMP-dependent downstream signaling, viability loss, and apoptosis. We developed a novel assay to assess cAMP efflux and performed screens to identify inhibitors. In an acute myeloid leukemia (AML) model, several identified compounds reduced cAMP efflux, appropriately modulated pathways that are responsive to cAMP elevation (cAMP-responsive element-binding protein phosphorylation, and deactivation of Very Late Antigen-4 integrin), and induced mitochondrial depolarization and caspase activation. Blocking adenylyl cyclase activity was sufficient to reduce effects of the most potent compounds. These compounds also decreased cAMP efflux and viability of B-lineage acute lymphoblastic leukemia (B-ALL) cell lines and primary patient samples, but not of normal primary peripheral blood mononuclear cells. Our data suggest that cAMP efflux is a functional feature that could be therapeutically targeted in leukemia. Furthermore, because some of the identified drugs are currently used for treating other illnesses, this work creates an opportunity for repurposing.

Method Modification Study for the Thermo Scientific SureTect™ Listeria Species Assay-Matrix Extension.

The Thermo Scientific™ SureTect™ Listeria species assay is a new real-time PCR assay for the detection of all species of Listeria in food and environmental samples. The assay was originally certified as Performance Tested Methods(SM) (PTM) 071304 in 2013. This report details the method modification study undertaken to extend the performance claims of the assay for matrixes of raw ground turkey, raw ground pork, bagged lettuce, raw pork sausages, pasteurized 2% fat milk, raw cod, pasteurized brie cheese, and ice cream. The method modification study was conducted using the AOAC Research Institute (RI) PTM program to validate the SureTect PCR assay in comparison to the reference method detailed in ISO 11290-1:1996 including amendment 1:2004. All matrixes were tested by Thermo Fisher Scientific (Basingstoke, United Kingdom). In addition, three matrixes (raw cod, bagged lettuce, and pasteurized brie cheese) were analyzed independently as part of the AOAC RI-controlled independent laboratory study by the University of Guelph, Canada. Using probability of detection statistical analysis, there was no significant difference in the performance between the SureTect assay and the International Organization for Standardization reference method for any of the matrixes analyzed in this study.

Corrigendum to "Detection of BRAF mutations from solid tumors using Tumorplex™ technology" [MethodsX 2 (2015), 316-322].

[This corrects the article DOI: 10.1016/j.mex.2015.06.002.].