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LAY ABSTRACT: What is already known about the topic?Parents and carers face many challenges following their child's autism diagnosis. They often look for information, and social and emotional support. There has been relatively little research into how best to provide this support and this means that there is no evidence to guide the delivery of services. Studies have suggested that an approach called Acceptance and Commitment Therapy can help parents and carers with their adjustment and emotional wellbeing.What does this article add?This article describes the development of a new group-based programme to address the diverse needs of caregivers after their child's autism diagnosis. The new programme was developed with caregivers, autistic people and professionals. It was called Empower-Autism and contained lots of information about autism and strategies to support autistic children, alongside therapeutic aspects based on Acceptance and Commitment Therapy. The programme was delivered to 29 parents/carers in three groups. Attendance at the groups was satisfactory. Both parents/carers and facilitators liked and valued the programme and found it accessible. They made suggestions for improvements. After the programme, parents and carers described improved wellbeing. They felt more positive and more connected to other people. They also described parenting their child in a more informed and sensitive way.Implications for practice, research or policyThe new programme is being tested within a large clinical trial. If there are positive results, the programme could be recommended for delivery and this would address an important gap in evidence-based practice.
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Studies of longevity rely on baseline life expectancy of reference genotypes measured in standardized conditions. Variation among labs, protocols, and genotypes makes longevity intervention studies difficult to compare. Furthermore, extending lifespan under suboptimal conditions or that of a short-lived genotype may be of a lesser theoretical and translational value than extending the maximal possible lifespan. Daphnia is becoming a model organism of choice for longevity research complementing data obtained on traditional models. In this study, we report longevity of several genotypes of a long-lived species D. magna under a variety of protocols, aiming to document the highest lifespan, factors reducing it, and parameters that change with age and correlate with longevity. Combining longevity data from 25 experiments across two labs, we report a strong intraspecific variation, moderate effects of group size and medium composition, and strong genotype-by-environment interactions with respect to food level. Specifically, short-lived genotypes show no caloric restriction (CR) effect, while long-lived ones expand their lifespan even further under CR. We find that the CR non-responsive clones show little correlation between longevity and two measures of lipid peroxidation. In contrast, the long-lived, CR-responsive clones show a positive correlation between longevity and lipid hydroperoxide abundance, and a negative correlation with MDA concentration. This indicates differences among genotypes in age-related accumulation and detoxification of LPO products and their effects on longevity. Our observations support the hypothesis that a long lifespan can be affected by CR and levels of oxidative damage, while genetically determined short lifespan remains short regardless.
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Tools to measure autism knowledge are needed to assess levels of understanding within particular groups of people and to evaluate whether awareness-raising campaigns or interventions lead to improvements in understanding. Several such measures are in circulation, but, to our knowledge, there are no psychometrically-validated questionnaires that assess contemporary autism knowledge suitable to the UK context. We aimed to produce a brief measure to assess between-respondent variability and within-respondent change over time. A pool of questionnaire items was developed and refined through a multi-stage iterative process involving autism experts and a lay sample. Attention was paid to face validity, clarity, consensus on correct responses, and appropriate difficulty levels. Initial validation data was obtained from a lay sample of 201 people. Difficulty and discrimination ability were assessed using item response theory and low-performing items were removed. Dimensionality was evaluated with exploratory factor analysis, which revealed a one-factor structure of the questionnaire. Further items were removed where they did not load strongly on their main factor. This process resulted in a final 14-item questionnaire called the Knowledge of Autism Questionnaire-UK. Internal consistency was satisfactory, and the final questionnaire was able to distinguish between parents of autistic people and those without an affiliation to autism. The KAQ-UK is a new, freely-available measure of autism knowledge that could be used to assess between-respondent variability and within-respondent change over time. Further evaluation and validation of its measurement properties are required.
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BACKGROUND: Factor XII (FXII) is a multifunctional protease capable of activating thrombotic and inflammatory pathways. FXII has been linked to thrombosis in extracorporeal membrane oxygenation (ECMO), but the role of FXII in ECMO-induced inflammatory complications has not been studied. We used novel gene-targeted FXII- deficient rats to evaluate the role of FXII in ECMO-induced thromboinflammation. METHODS: FXII-deficient (FXII-/-) Sprague-Dawley rats were generated using CRISPR/Cas9. A minimally invasive venoarterial (VA) ECMO model was used to compare wild-type (WT) and FXII-/- rats in 2 separate experimental cohorts: rats placed on ECMO without pharmacologic anticoagulation and rats anticoagulated with argatroban. Rats were maintained on ECMO for 1 hour or until circuit failure occurred. Comparisons were made with unchallenged rats and rats that underwent a sham surgical procedure without ECMO. RESULTS: FXII-/- rats were maintained on ECMO without pharmacologic anticoagulation with low resistance throughout the 1-hour experiment. In contrast, WT rats placed on ECMO without anticoagulation developed thrombotic circuit failure within 10 minutes. Argatroban provided a means to maintain WT and FXII-/- rats on ECMO for the 1-hour time frame without thrombotic complications. Analyses of these rats demonstrated that ECMO resulted in increased neutrophil migration into the liver that was significantly blunted by FXII deficiency. ECMO also resulted in increases in high molecular weight kininogen cleavage and complement activation that were abrogated by genetic deletion of FXII. CONCLUSIONS: FXII initiates hemostatic system activation and key inflammatory sequelae in ECMO, suggesting that therapies targeting FXII could limit both thromboembolism and inopportune inflammatory complications in this setting.
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Endometriosis is a prevalent gynecologic condition associated with pelvic pain and infertility characterized by the implantation and growth of endometrial tissue displaced into the pelvis via retrograde menstruation. The mouse is a molecularly well-annotated and cost-efficient species for modeling human disease in the therapeutic discovery pipeline. However, as a non-menstrual species with a closed tubo-ovarian junction, the mouse poses inherent challenges as a preclinical model for endometriosis research. Over the past three decades, numerous murine models of endometriosis have been described with varying degrees of fidelity in recapitulating the essential pathophysiologic features of the human disease. We conducted a search of the peer-reviewed literature to identify publications describing preclinical research using a murine model of endometriosis. Each model was reviewed according to a panel of ideal model parameters founded on the current understanding of endometriosis pathophysiology. Evaluated parameters included method of transplantation, cycle phase and type of tissue transplanted, recipient immune/ovarian status, iterative schedule of transplantation, and option for longitudinal lesion assessment. Though challenges remain, more recent models have incorporated innovative technical approaches such as in vivo fluorescence imaging and novel hormonal preparations to overcome the unique challenges posed by murine anatomy and physiology. These models offer significant advantages in lesion development and readout toward a high-fidelity mouse model for translational research in endometriosis.