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Background: Child protective services (CPS), or their equivalent, have statutory power to remove children from birth parents in instances of child abuse, neglect, or concerns around parenting capacity via public family care proceedings. Parents who have children subject to proceedings, ‘birth parents’, often have complex health and social care needs. Objective: We aimed to review what is known about the health needs of birth parents and the interventions implemented to support these health needs. Methods: We searched PubMed, Scopus, and grey literature using a systematic strategy of key concepts “health”, “care proceedings”, and “parents”. We included all publications in English that reported parental health in the context of care proceedings from the 1st of January 2000 to the 1st of March 2021. Results: Included studies (n = 61) reported on maternal health (57 %) or the health of both parents (40 %), with only one study reporting on fathers alone. We conceptually categorised parental health need (n = 41) into i) mental health, ii) physical health, iii) substance misuse, iv) developmental disorders, and v) reproductive health. Health inequities and poor access to services were described across all categories, with longstanding issues often pre-dating proceedings or the child’s birth. All interventions supporting parental health (n = 20) were targeted at mothers, with some supporting fathers (n = 8), formally or informally. We grouped similar interventions into three types: alternative family courts, wrap-around services, and specialist advocacy/peer support. Conclusions: Parents who have children subject to care proceedings have complex health needs that pre-date CPS concerns. The studies included in our review strongly suggest that health issues are exacerbated by child removal, triggering deteriorations in mental health, poor antenatal health for subsequent pregnancies, and avoidable mortality. Findings highlight the need for targeted and timely intervention for parents to improve whole-family outcomes. There are models that have been designed, implemented, and tested using relationship-based, trauma-informed, multidisciplinary, family-focused, and long-term approaches.

Mutations in the ABCB4 gene are associated with failure of bile acid emulsification leading to cholestatic liver disease. Presentations range from progressive familial intrahepatic cholestasis type 3 (PFIC3) in childhood, to milder forms seen in adulthood.We sought to characterize adult disease with particular reference to histology which has been hitherto poorly defined.Four unrelated adults (three female, mean age 39 years) and three sisters presenting with cholestatic liver disease in adulthood, associated with variants in the ABCB4 gene, were identified. Clinical review and detailed blinded histopathological analysis were performed.Two novel pathogenic ABCB4 variants were identified: c.620 T G, p.(Ile207Arg) and c.2301dupT, p.(Thr768TyrfsTer26). Sub-phenotypes observed included low-phospholipid-associated cholelithiasis syndrome (LPAC), intrahepatic cholestasis of pregnancy (ICP), drug-induced cholestasis, idiopathic adulthood ductopenia, and adult PFIC3. Of note, 5/7 had presented with gallstone complications (4 meeting LPAC definition) and 4/6 females had a history of ICP. Considerable overlap was observed phenotypically and liver transplantation was required in 3/7 of patients. Histologically, cases generally demonstrated ductopenia of the smaller tracts, mild non-ductocentric portal inflammation, bilirubinostasis, significant copper-associated protein deposition, and varying degrees of fibrosis.Adults with ABCB4 mutations may harbor a spectrum of cholestatic disease phenotypes and can progress to liver transplantation. We observed a distinct histological pattern which differs from classical biliary disease and describe two novel pathogenic ABCB4 variants. ABCB4 sequencing should be considered in patients with relevant cholestatic phenotypes and/or suggestive histology; accurate diagnosis can guide potential interventions to delay progression and inform family screening.

To identify the attitudes and perspectives of speech pathologists, occupational therapists and physiotherapists on using telehealth videoconferencing for service delivery to children with developmental delays.Systematic Literature Review.An electronic search of databases Scopus, CINAHL, MEDLINE, PEDro, Speechbite, OTseeker and ScienceDirect was undertaken in October 2020. Articles were compared with eligibility criteria by 2 authors. All articles were appraised for quality and level of evidence.Fourteen studies were deemed to be eligible. Results were synthesised using a narrative analysis. The themes identified were technology, self-efficacy, replacement of face-to-face services, time management, relationships, access and family-centred care. Each of these themes was seen as both a potential barrier and a facilitator when trying to provide services via telehealth.The results in this review cannot be generalised due to small sampling size, low response rates, lack of maximum variation sampling and under-representation of occupational therapists and physiotherapists. Study design was either mixed-methods survey or interview or only survey or interview. Risk of bias in studies was high. Further research is required including comparison studies and cost-benefit analysis.

Caregivers of people living with dementia often report greater symptoms of depression, anxiety, and burden. Guided by the Stress Process Model, the study examined the impact of self-compassion on these key psychosocial well-being outcomes in a sample of dementia caregivers (N=99). Participants were 66.7% female, 67.7% White, and 74% were children/in law or grandchildren/in law, with a mean age of 38.61. Findings indicated self-compassion was a significant and unique predictor of symptoms of depression (β = -.25, p = .03), anxiety (β = -.36, p = .01), and burden (β = -.25, p = .02). Additional analyses found support for dysfunctional coping meditating the relationship between self-compassion and caregiver burden ((B = -.20, SE = .06, 95%CI[-.3242, -.0924] dysfunctional coping mediating the relationship between self-compassion and anxiety (B = -.16, SE = .05, 95%CI[-.2257, -.0302] and emotion-focused coping meditating the relationship between self-compassion and depression (B = -.06, SE = .03, 95%CI[-.1388, -.0045]. Results demonstrate the important role of self-compassion along with the impact of coping style on psychosocial well-being outcomes. Discussion will highlight the theoretical implications of these findings along with how these results can be used to develop efficacious interventions for caregivers of persons with dementia. Specifically, tailoring an intervention for dementia caregivers grounded in self-compassion theory as well as Compassion Focused Therapy and Mindful Self-Compassion Therapy may assist caregivers in developing a self-compassionate mindset and skills to more effectively cope with caregiving challenges.

Over 50 million informal caregivers provide care to an older adult age 50 or older. Negative financial impacts include significant out-of-pocket expenses, decreased income and future earnings. The program, Managing Money: A Caregiver’s Guide to Finances, was developed to address the lack of evidence-based programs and evaluated using a randomized control trial across 5 time points: Time 1 (baseline); Time 2 (after condition completion); Time 3 (30 days after Time 2); Time 4 (60 days after Time 2); and Time 5 (90 days after Time 2). The mean age of participants was 55.45 (SD=14.85); 80% female; 72% White and 69% married. Forty-six percent provided care to their parent/in-law, 36% to a spouse/partner, and 40% were employed full-time. Participants were randomly assigned to the program (N=76) or waitlist condition (N=98). No significant differences on demographic or care context variables were found between conditions. A 2 x 5 repeated measures analyses examined significant change across time based on condition. For significant outcomes, post-hoc analyses examined whether change was short-term (T2,T3); long-term (T4,T5); or both. Results found: 1) significant short- and long-term improvements for Unmet Needs (F(1,4)=8.34,p=.01); Self-efficacy (F(1,4)=4.27,p=.01); and Behavioral Intentions (F(1,4)=3.63,p=.01) and 2) significant long-term improvements for Unmet Needs Distress (F(1,4)=5.82,p=.01) and Behavioral Actions (F(1,4)=4.55,p=.01). Results indicated the program was efficacious in positively impacting key financial preparedness measures. Discussion highlights key study elements including program accessibility and scalability; generalizability of findings and limitations; and contextualizing results within the larger literature.

Purpose: The purposes of the study are to (1) determine what barriers and facilitators physiotherapists perceive to using telehealth, (2) to determine willingness to use and (3) to determine perspectives on training in the use of telehealth. Method: This is a qualitative semi structured interview and focus group design. Participants were recruited from the first stage of the larger research process using purposive sampling. A semi structured guide was used to facilitate discussion of shared experiences and to allow themes to emerge from the discussion. Results: Thematic analysis was used to synthesise frequent and important themes. Ten participants took part in either a focus group (n=7) or interview (n=3). Nine main themes identified were split into barriers and facilitators. Facilitators were the right family, right child, adequate technology and space, and collaboration. Barriers were technology, time management, lack of physical touch, lack of organisational support, and work environment. Conclusion: Results suggest that physiotherapists working with children with developmental delay consider telehealth to be unsuitable to replace face-to-face therapy entirely but are willing to use it to provide follow up services to the right family and the right child. Physiotherapists in the study were positive about telehealth’s potential to improve services to children in rural areas. Physiotherapists said that specific physiotherapy training in telehealth was currently lacking.

Oxidative stress and endothelial dysfunction contribute substantially to the pathogenesis of preeclampsia (PE). Decidual mesenchymal stem/stromal cells (DMSC), reportedly reduce endothelial cell dysfunction and alleviate PE-like symptoms in a murine model. However, as a therapeutic strategy, the use of whole DMSC presents significant technical limitations, which may be overcome by employing DMSC-secreted extracellular vesicles (DMSC_EV). DMSC_EV restoration of endothelial dysfunction through a paracrine effect may alleviate the clinical features of PE. Objective To determine whether DMSC-secreted, extracellular vesicles (DMSC_EV) restore endothelial cell function and reduce oxidative stress. Methods DMSC were isolated from the placentae of uncomplicated term pregnancies and DMSC_EV prepared by ultracentrifugation. Human umbilical vein endothelial cells (HUVEC) were treated with bacterial lipopolysaccharide (LPS), or with serum from PE patients, to model the effects of PE. DMSC_EV were then added to treated HUVEC and their growth profiles, inflammatory state, and oxidative stress levels measured. Results DMSC_EV displayed characteristic features of extracellular vesicles. In both LPS- and PE serum-treatment models, addition of DMSC_EV significantly increased HUVEC cell attachment and proliferation, and significantly reduced production of pro-inflammatory cytokine IL-6. The addition of DMSC_EV to LPS-treated HUVEC had no significant effect on total antioxidant capacity, superoxide dismutase levels or on lipid peroxidation levels. In contrast, the addition of DMSC_EV to PE serum-treated HUVEC resulted in a significant reduction in levels of lipid peroxidation. Conclusion Addition of DMSC_EV had beneficial effects in both LPS- and PE serum- treated HUVEC but the two treatment models to induce endothelial cell dysfunction showed differences. The LPS treatment of HUVEC model may not accurately model the endothelial cell dysfunction characteristic of PE. Human cell culture models of PE show that DMSC_EV improve endothelial cell dysfunction in PE, but testing in in vivo models of PE is required.

Caregivers are often financially impacted, through health care costs, long-term care costs, and decreased income. A financial literacy program, Managing Money: A Caregiver’s Guide to Finances, was developed to provide information on financial impacts in caregiving. The virtual program was delivered synchronously with a live presenter through an online platform and was rated with high acceptability. The virtual program was then shifted to an online format. Changes included removing the live presenter and group format in favor of a voiceover and self-paced movement, the addition of videos, and online resources. The asynchronous, self-paced online delivery of the program was evaluated through a survey of 146 caregivers. Participants had a mean age of 45.85 (SD=5.65); 55% female; 75% White; 46% cared for their grandparent and 45% to their parent. A Likert scale was utilized to indicate satisfaction with the program (1=strongly disagree, 5=strongly agree). Overall, participants indicated that the program provided important information on managing money (M=3.97, SD=.83); helped to understand the content (M=3.89, SD=.91); was easy to read and understand (M=3.99, SD=.90); and would recommend the program (M=3.91, SD=.84). The explanation of content areas were rated on a Likert scale (1=poor, 4=excellent); participants rated areas including having conversations about finances (M=3.05, SD=.80); avoiding financial fraud and abuse (M=2.98, SD=.81); covering care costs (M=2.98, SD=.81); and organizing legal plans (M=3.09, SD=.80). Participants reported no difficulties that needed to be resolved when moving through the program. Overall, both the virtual and online formats were acceptable and feasible to caregiving populations.

Background Around a third of people with schizophrenia or related serious mental illness will be a parent. Both the parents and the children in this population are at increased risk of adverse outcomes due to parental mental illness. Parenting interventions are known to improve parenting skills and decrease child disruptive behaviour. This systematic review aimed to synthesise the evidence base for parenting interventions designed specifically for parents who have schizophrenia or related serious mental illness. Objectives To assess the effects of parenting interventions for people with schizophrenia or related serious mental illness. Search methods On 10 February 2021 we searched the Cochrane Schizophrenia Group's Study‐Based Register of Trials, which is based on the following: Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), ClinicalTrials.Gov, Embase, International Standard Randomised Controlled Trial Number (ISRCTN), MEDLINE, PsycINFO, PubMed, and the World Health Organization International Clinical Trials Registry Platform. Selection criteria Eligible studies were randomised controlled trials (RCTs) that compared parenting interventions with a control condition for people with schizophrenia or related serious mental illness with a child between the ages of 0 and 18 years. Data collection and analysis We independently inspected citations, selected studies, extracted data and appraised study quality. We assessed risk of bias for included studies. Main results We only included one trial (n = 50), and it was not possible to extract any data because the authors did not provide any means and standard deviations for our outcomes of interest; they only reported whether outcomes were significant or not at the 0.05 level. Three domains of the trial were rated as having a high risk of bias. Authors' conclusions The only included trial provided inconclusive evidence. There is insufficient evidence to make recommendations to people with schizophrenia (or related serious mental illness) or clinicians, or for policy changes. Although there is no RCT evidence, parenting interventions for people with schizophrenia or related serious mental illness have been developed. Future research should test these in RCTs in order to improve the evidence base for this population.

The objective of this study was to thematically synthesize literature about specific in-session therapeutic actions occurring for people with Cluster B personality disorder attending arts therapies. Studies reporting on arts therapies treatment for people with a diagnosis of personality disorder were searched in Embase, Medline, PubMed and grey sources until June 2017. Search yielded 167 records. 32 studies were included in the analysis. Data synthesis was conducted by using extracts from the literature search which were coded and then subject to a thematic analysis and synthesis. The codes were then discussed and agreed by the research team. The thematic analysis and synthesis resulted in seven overarching themes relating to: (1) Processing interpersonal experiences (2) Processing emotions (3) Developing agency (4) Symbolising (5) Structuring experience (6) Cognitive reappraisal, and (7) Developing a shared experience. This thematic synthesis provides some evidence that there are thematic similarities in terms of primary areas of therapeutic action and the relationship between the therapeutic action and the perceived effects of engaging in arts therapies. Our findings suggest that literature about in-session therapeutic actions focus mostly on processing interpersonal experiences and the largest frequency of coded excerpts concerning the perceived effect of engaging in arts therapies was in the area of processing emotions.

Background: Endoscopy within 24 hours of admission (early endoscopy) is a quality standard in acute upper gastrointestinal bleeding (AUGIB). We aimed to audit time to endoscopy outcomes and identify factors affecting delayed endoscopy (>24h of admission). Methods: This prospective multicentre audit enrolled patients admitted with AUGIB who underwent inpatient endoscopy between Nov-Dec 2017. Analyses were performed to identify factors associated with delayed endoscopy, and to compare patient outcomes, including length of stay and mortality rates, between early and delayed endoscopy groups. Results: Across 348 patients from 20 centres, the median time to endoscopy was 21.2h (IQR 12.0- 35.7), comprising median admission to referral and referral to endoscopy times of 8.1h (IQR 3.7- 18.1) and 6.7h (IQR 3.0-23.1) respectively. Early endoscopy was achieved in 58.9%, although this varied by centre (range: 31.0% - 87.5%, p=0.002). On multivariable analysis, lower Glasgow-Blatchford score, delayed referral, admissions between 7am-7pm or via the Emergency Department were independent predictors of delayed endoscopy. Early endoscopy was associated with reduced length of stay (median difference 1d; p= 0.004), but not 30-day mortality (p=0.344). Conclusions: The majority of centres did not meet national standards for time to endoscopy. Strategic initiatives involving acute care services may be necessary to improve this outcome.

Over 40 million informal caregivers provide care to adults aged 50 or older with a chronic illness. In addition to the negative health and well-being impact, caregivers experience financial difficulties including lost income, retirement benefits, future earnings, and unanticipated out-of-pocket costs. Few evidence-informed programs exist to assist caregivers in understanding and managing these financial tasks. This poster presents preliminary acceptability data from 71 caregivers who completed the newly developed Managing Money: A Caregiver’s Guide to Finances program. The 60-minute program was delivered online by trained community educators and addressed caregiving costs/impacts; future planning; initiating conversations; avoiding financial abuse/fraud; and identifying needs. Participants (Mage = 59.45, SD = 11.31) were 87.32% female with 77.46% self-identified as White, 9.86%, as Black, and 8.45% as Hispanic/Latino. Using a Likert scale (1=strongly disagree to 5=strongly agree), participants indicated the program: 1) identified financial challenges (M= 4.11 ; SD = 0.73); 2) provided information for managing money (M = 3.99; SD = 0.64); 3) content was easy to read/understand (M = 4.49; SD = 0.61); 4) program length was appropriate (M = 4.18; SD= 0.68); and 5) activities were helpful (M = 4.13; SD = 0.69). Participants rated the program as very important (M = 4.54; SD = 0.82) and would highly recommend (M = 4.52; SD = 0.53). Results indicated the program was well-received by participants and highly acceptable. Discussion will highlight key program features designed to promote acceptability along with the importance of measuring acceptability for large-scale implementation along with next research steps.

Background The ActualHCA™ system continuously monitors the activity, temperature and behavior of group-housed rats without invasive surgery. The system was validated to detect the contrasting effects of sedative and stimulant test agents (chlorpromazine, clonidine and amphetamine), and compared with the modified Irwin test (mIT) with rectal temperature measurements. Methods Six male Han Wistar rats per group were used to assess each test agent and vehicle controls in separate ActualHCA™ recordings and mIT. The mIT was undertaken at 15, 30 mins, 1, 2, 4 and 24 h post-dose. ActualHCA™ recorded continuously for 24 h post-dose under 3 experimental conditions: dosed during light phase, dark phase, and light phase with a scheduled cage change at the time of peak effects determined by mIT. Results ActualHCA™ detected an increase stimulated activity from the cage change at 1-2 h post-dose which was obliterated by chlorpromazine and clonidine. Amphetamine increased activity up to 4 h post-dose in all conditions. Temperature from ActualHCA™ was affected by all test agents in all conditions. The mIT showed effects on all 3 test agents up to 4 h post-dose, with maximal effects at 1-2 h post-dose. The maximal effects on temperature from ActualHCA™ differed from mIT. Delayed effects on activity were detected by ActualHCA™, but not on mIT. Conclusions Continuous monitoring has the advantage of capturing effects over time that may be missed with manual tests using pre-determined time points. This automated behavioural system does not replace the need for conventional methods but could be implemented simultaneously to improve our understanding of behavioural pharmacology.

Purpose Mental health problems and substance misuse are common among the mothers of children who experience court-mandated placement into care in England, yet there is limited research characterising these health needs to inform evidence-based policy. In this descriptive study, we aimed to generate evidence about the type, severity, and timing of mental health and substance misuse needs among women involved in public family law proceedings concerning child placement into care (‘care proceedings’). Methods This is a retrospective, matched cohort study using linked family court and mental health service records for 2137 (66%) of the 3226 women involved in care proceedings between 2007 and 2019 in the South London and Maudsley NHS Mental Health Trust (SLaM) catchment area. We compared mental health service use and risk of dying with 17,096 female-matched controls who accessed SLaM between 2007 and 2019, aged 16–55 years, and were not involved in care proceedings. Results Most women (79%) were known to SLaM before care proceedings began. Women had higher rates of schizophrenia spectrum disorders (19% vs 11% matched controls), personality disorders (21% vs 11%), and substance misuse (33% vs 12%). They were more likely to have a SLaM inpatient admission (27% vs 14%) or to be sectioned (19% vs 8%). Women had a 2.15 (95% CI 1.68–2.74) times greater hazard of dying, compared to matched controls, adjusted for age. Conclusion Women involved in care proceedings experience a particularly high burden of severe and complex mental health and substance misuse need. Women’s increased risk of mortality following proceedings highlights that interventions responding to maternal mental health and substance misuse within family courts should offer continued, long-term support.

Background and Aims The ABCB4 gene encodes the floppase, multidrug-resistance p-glycoprotein 3 (MDR3), which transports phosphatidylcholine (PC) to the outer leaflet of the cell membranes lining the bile canaliculi. PC combines with bile acids in the canalicular lumen to form micelles, thus preventing the emulsification action of bile acids damaging the canalicular epithelium. Mutations in the ABCB4 gene are associated with failure of this process leading to cholestatic liver disease. Presentations range from progressive familial intrahepatic cholestasis type 3 (PFIC3), most commonly presenting in childhood, to less severe forms typically presenting in adulthood. Adult phenotypes are poorly characterised hence we sought to examine in detail a series of patients with ABCB4 variants presenting to our institution. Methods Six unrelated adults with ABCB4 variants (four female, mean age 39 years) presenting with a cholestatic liver disorder were identified. In addition, three sisters with adult-onset cholestasis (labelled as PFIC3), one of whom was compound heterozygous for ABCB4, were studied. As well as case note review, detailed sequencing and histopathological analysis were performed. Results Cases were sub-phenotyped as follows: drug-induced cholestasis, idiopathic adulthood ductopenia, refractory primary biliary cholangitis (PBC) and adult PFIC3. 6/9 had presented with gallstone complications and 5/7 females had a history of intrahepatic cholestasis of pregnancy (ICP). Liver transplantation was required for two out of these nine patients, with another currently wait-listed. Histologically, all cases demonstrated a degree of ductopenia, affecting the smallest interlobular ducts only, copper-associated protein and fibrosis. Portal inflammation was consistently present but of note non-ductocentric. At least one previously unreported pathogenic ABCB4 variant was observed (c.620T>G, p.(Ile207Arg)) and ‘adult PFIC3’ was associated with compound, rather than simple, heterozygosity. Conclusion We describe a range of adult phenotypes associated with pathogenic variants, including novel, in the ABCB4 gene. A distinct histological pattern was observed which differs from classical PBC and primary sclerosing cholangitis (PSC), in some cases overlapping with vanishing bile duct syndromes. Cholestatic liver disease in adults merits genetic analysis, particularly where there is a history of early gallstone disease or ICP, a relevant family history or where the histological profile described is present. Family members should be screened and liver transplantation may be required in more severe cases.

Background: The use of new technologies and methodologies in young people’s mental health research is needed to allow more frequent and reliable sampling. Mobile applications and e-platforms create exciting potential for the collection of large-scale cohort data, however there are various feasibility and ethical issues to consider. Consultation with young people is needed to inform the research agenda, and ensure these technologies are engaging, useful and safe. This article describes the process of Public and Patient Involvement (PPI) with a sample of young people in London, with the aim of i) informing the development of a mood-monitoring e-platform, and ii) providing feedback and advice for researchers developing web-based technologies in the mental health field. Methods: A total of 26 young people were consulted across four advisory group co-design sessions. All young people were students enrolled at one of the participating London based sixth form colleges, and voluntarily attended a workshop session. Audio recordings of the sessions were analysed using a thematic analysis framework. Results: We found that young people were engaged in discussions around mobile health technologies and valued the opportunity to collaborate throughout the early stages of the development process The advisory groups identified key considerations for future web-development work to encourage engagement and prolonged use, including, the promotion of trust and transparency, consideration of accessibility, provision of support, production of engaging and functional design, and acknowledgment of specific contextual influences surrounding young people’s wellbeing. Conclusions: Involving young people in the development process of e-health technologies contributes to optimising the successful adoption and prolonged usage of new methodologies. The thematic map and informant examples can be used to guide researchers interested in developing web-based technologies in the mental health field and will be directly applicable to the development of a mood-monitoring e-platform.

Caregivers of Individuals with Dementia (IWDs) often face increased rates of depression, anxiety, and burden because of their role as caregiver. Self-compassion, a construct centered around self-kindness and understanding has not been well studied within the caregiving population. The present study was aimed at understanding the relationship between self-compassion and the psychosocial outcomes of burden, depression, and anxiety. Strong relationships between self-compassion and these outcomes have been established in other populations, but these relationships have not been studied with the dementia caregiving population. A diverse sample of dementia caregivers providing over 5 hours of care per week were recruited through CloudResearch and MTurk (N = 99). Participants were aged 18 to 69 years (M = 38.61) and 66.7% were female. 67.7% were White, 13.1% were Black, and 8.1% were Asian. 73% were children/in law or grandchildren/in law of the individual with dementia and 12% were a close friend of the individuals with dementia. The individuals with dementia had an average age of 73.88 years. Results of multiple regression models showed that self-compassion was a significant predictor of depression (β = -.25, p = .025), anxiety (β = -.36, p = .001), and burden (β = -.25, p = .023) even while controlling for other constructs including self-esteem, types of coping, and IWD impairment level. Self-compassion will be discussed as a novel contribution to the caregiving literature in furthering our understanding of well-being predictors and how to target self-compassion as a modifiable factor for offsetting the negative impacts of caregiving.

Research supports the inclusion of individuals with mild to moderate dementia (IWDs) as study participants in providing reliable and valid self-report information about their illness experience. However, no clear guidelines or tools exist for determining study eligibility with many studies relying on brief cognitive measures (e.g., MMSE). The literature suggests not all individuals with mild/moderate dementia can participate and some individuals with severe symptoms of dementia can participate. This study piloted a new measure designed to assess whether IWDs can participate in self-report data protocols. The measure consists of 10 questions that assess relatively in-tact cognitive processes hypothesized for successful participation. Example questions include: “What is your favorite holiday?” and “Give an example of a sad occasion/event”. Questions are scored as ‘correct’ or ‘incorrect’ and summed for a total score. To examine the descriptive characteristics of the measure, IWDs (n=18) completed the measure along with the MMSE and, for some IWDs (n=12), several self-report measures. Scores on the new measure ranged from 0-10, with a M=7.61; SD=2.75. MMSE scores ranged from 2-22, with a M=13.39; SD=6.47. A significant correlation (r = .86, p< .001) was found with the MMSE, indicating a high degree of relatedness but not complete construct overlap. Results also highlight the variability of the measure, with incorrect responses ranging from 3 to 6 across participants. Additional properties of the measure will be discussed along with highlighting how study findings fit with recommendations from 2020 NIA Research Summit on Dementia Care and next-steps in refinement and testing.

The effects on fetal weights and maternal health of taking 32 μL blood microsamples at the end of organogenesis in a mouse embryofetal development (EFD) study design was investigated with the aim of reducing satellite animal usage. The effects of warming, handling and sampling either 3 or 6 times on gestation day 16 was evaluated. Maternal body weight gain was transiently reduced when animals underwent warming and handling with or without microsampling. Fetal weights on gestation day 18 were reduced after 6 occasion warming and handling alone or taking samples, but not when sampling was limited to 3 timepoints. Taking 3 microsamples of 32 μL had no permanent adverse effects on maternal health or toxicologically significant effects on fetal development (measured by fetal weights). This regimen could be used to generate composite toxicokinetic profiles using only 6 main test animals in mouse EFD studies provided sampling procedures were matched across groups.

Background Accurate prediction of spontaneous preterm labor/preterm birth in asymptomatic women remains an elusive clinical challenge because of the multi-etiological nature of preterm birth. Objective The aim of this study was to develop and validate an immunoassay-based, multi-biomarker test to predict spontaneous preterm birth. Materials and Methods This was an observational cohort study of women delivering from December 2017 to February 2019 at 2 maternity hospitals in Melbourne, Australia. Cervicovaginal fluid samples were collected from asymptomatic women at gestational week 16+0−24+0, and biomarker concentrations were quantified by enzyme-linked immunosorbent assay. Women were assigned to a training cohort (n = 136) and a validation cohort (n = 150) based on chronological delivery dates. Results Seven candidate biomarkers representing key pathways in utero-cervical remodeling were discovered by high-throughput bioinformatic search, and their significance in both in vivo and in vitro studies was assessed. Using a combination of the biomarkers for the first 136 women allocated to the training cohort, we developed an algorithm to stratify term birth (n = 124) and spontaneous preterm birth (n = 12) samples with a sensitivity of 100% (95% confidence interval, 76−100%) and a specificity of 74% (95% confidence interval, 66−81%). The algorithm was further validated in a subsequent cohort of 150 women (n = 139 term birth and n = 11 preterm birth), achieving a sensitivity of 91% (95% confidence interval, 62−100%) and a specificity of 78% (95% confidence interval, 70−84%). Conclusion We have identified a panel of biomarkers that yield clinically useful diagnostic values when combined in a multiplex algorithm. The early identification of asymptomatic women at risk for preterm birth would allow women to be triaged to specialist clinics for further assessment and appropriate preventive treatment.

Background Evaluation of the effects of candidate drugs on the nervous system in preclinical safety pharmacology studies utilises a global neurobehavioral assessment, usually in the rat. This either takes the form of the functional observational battery (FOB) or modified Irwin Test, both of which evaluate effects across 4 functional domains: autonomic, neuromuscular, sensorimotor and behavioral. Although there is a great deal of overlap in the parameters they address, the two tests approach the assessments slightly differently. We undertook a broad pharmacological validation of both the FOB and the Irwin test, and compared the two outcomes. Methods Male rats (6 per treatment group) were used to assess each of 12 reference drugs alongside vehicle controls in separate FOB and Irwin studies. The drugs compared in the two study types were chlorpromazine, chlordiazepoxide, clonidine, baclofen, (+)-amphetamine, harmaline, 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone, physostigmine, picrotoxin, yohimbine and atropine. There is a high degree of semantic equivalence in the parameters assessed in the autonomic domain between the two tests, with a lower degree of equivalence for neuromuscular and behavioral domains, whereas sensorimotor reflex testing in the FOB is far more extensive than in the Irwin test. Results Across the set of reference drugs, concordance between the two tests was generally good across the 4 functional domains at the ‘domain’ level (i.e., detecting ‘an effect’), whereas there was generally a poor concordance at the individual parameter level. However, this was partially explained by variability between repeated studies on a single reference drug using the same test (FOB or Irwin). Conclusions Both tests are ‘fit-for-purpose’ in detecting effects of candidate drugs on the nervous system. We would encourage the global safety pharmacology community to consider whether (a) the tests could be combined into one industry standard; (b) candidate drugs could be triaged according to CNS penetration, with the level of scrutiny in the CNS core battery assessment adjusted accordingly and (c) whether new home cage technology could be applied to semi-automate the preclinical neurobehavioral assessment.

Although much research suggests that intergroup contact reduces prejudice, less research has examined the effects of contact on prosocial intergroup bystander behaviors. The current study examined mediators between White undergraduate women’s (N = 139) contact with racial/ethnic minority group members and their intent to help a Black woman at risk for sexual assault. As expected, White women who had more frequent and higher quality contact reported greater intent to intervene. Results showed that the effect of quality intergroup contact was mediated by diversity beliefs, or the attitude that cultural heterogeneity leads to favorable outcomes. These results suggest that promoting high-quality opportunities for intergroup contact and education regarding cultural diversity could promote the safety of racially and ethnically diverse students on predominantly White campuses.

Including individuals with dementia as participants in research studies can be a challenge given the cognitive symptoms experienced, including difficulties with attention, memory, language, and executive functioning and behavioral symptoms, such as agitation and frustration. Researchers, however, have begun to include individuals with dementia as more active participants in the research process. Specifically, individuals with dementia have provided self-report information about their illness experience, including how they cope and manage with their illness and how illness-related strains are related to psychosocial outcomes. Researchers also have starting using self-report data collection protocols instead of proxy-report measures to assess the impact of non-pharmacological interventions developed for individuals with dementia on well-being outcomes such as depressive symptoms, unmet needs, and relationship strain. To date, however, there are no clear guidelines or ‘best practices’ to assist researchers in developing study protocols that facilitate the inclusion and participation of individuals with dementia. This poster will present findings from a systematic literature review of studies that have successfully included individuals with dementia as research participants. Key areas examined include: 1) the focus and type of research question studied; 2) the use and type of cognitive screening tools for determining study eligibility; 3) implementation of qualitative versus quantitative research designs; 4) objective versus subjective measures; 5) data collection tools; 6) psychometric evidence of data obtained; and 7) how data have been analyzed. Findings highlight the importance of collecting data directly from individuals with dementia to further understand the illness experience and assess the impact of non-pharmacological interventions.

A 2-year prospective, longitudinal study of 10 suckler sheep flocks in Great Britain was run to identify factors associated with acute mastitis (AM) and chronic mastitis, and their impact on lamb growth rate. Data were collected on AM, intramammary masses (IMM; a marker for chronic mastitis), udder and teat conformation, teat lesions, body condition, ewe nutrition, litter size, lamb weight and general flock management. Each flock was visited twice each year, approximately 4 weeks before lambing and 9 weeks into lactation, for two years and all ewes present at a visit were examined. There were 7021 examinations in total. AM was reported in 2.1–3.0% of ewes/year; this ranged from 0.0% to 37.1% by flock. IMM were detected in 4.7% of ewes in pregnancy and 10.9% of ewes in lactation. Once an IMM had been detected there was an increased risk of future IMM although IMM were not consistently present. The majority of ewes had good udder conformation to suckle lambs. Factors associated with AM, IMM in pregnant and lactating ewes, udder conformation and lamb daily live weight gain were explored using mixed effect multivariable models. An increased risk of AM was associated with underfeeding protein in pregnancy (OR 4.05), forward pointing teats (OR 2.54), downward pointing teats (OR 4.68), rearing ≥ 2 lambs (OR 2.65), non-traumatic teat lesions (OR 2.09); and marginally associated with the presence of IMM. An increased risk of IMM in lactation was associated with AM during lactation (OR 12.39), IMM in pregnancy (OR 4.79), IMM in the previous lactation (OR 4.77), underfeeding energy in pregnancy (OR 6.66) and traumatic teat lesions (OR 2.48). An increased risk of IMM in pregnancy was associated with IMM in the previous pregnancy, IMM in the previous lactation and underfeeding energy in the previous lactation (OR 2.95). Lower lamb daily live weight gain was associated with traumatic teat lesions, IMM in lactation (−0.01 kg/day) and AM (−0.04 kg/day). We conclude that inadequate nutrition is an important cause of mastitis in suckler ewes which farmers could address in part using current nutritional guidelines but further work is needed. The relationship between AM and IMM indicates that separating or culling ewes with IMM would help reduce AM.\ud

Limited toxicokinetic data is generated during modified Irwin screen and whole body plethysmography safety pharmacology studies, due to disturbance of primary endpoints by standard blood sampling methods. We evaluated if incorporation of microsampling would impact on data quality, as providing toxicokinetic data from main test animals could reduce the need for satellite animals. Methods A modified Irwin screen was performed, testing oral clonidine (0, 0.03, 0.1, or 0.3 mg/kg). One cohort of rats per dose level underwent standard blood sampling (post-4 h Irwin assessment), and another cohort underwent microsampling after the 0.5, 1, 2, 4 and 24 h Irwin assessments. The respiratory effects of oral theophylline (0 or 10 mg/kg) and oral baclofen (0 or 5 mg/kg), were tested using whole body plethysmography. Groups of animals underwent standard blood sampling (at end of recording at 4 h post-dose) or microsampling at either 0.5 h or 1 h intervals (4 or 8 microsamples, respectively). Results Microsampling did not impact on the quality of the data generated. The expected effects of clonidine on behavioural parameters, and of theophylline and baclofen on changes in ventilatory parameters were observed at a similar magnitude and duration independent of sampling method. Discussion The incorporation of multiple capillary microsamples into the modified Irwin or respiratory study did not adversely affect the primary endpoints. The capillary microsampling method is a refinement in blood sampling technique which can easily be adapted into safety pharmacology studies to generate pharmacokinetic profiles within the same animal as the primary data, thus enhancing scientific robustness and reducing the satellite animals required.

Background Preliminary studies have indicated that music therapy may benefit children with autism spectrum disorders (ASD). Objectives To examine the effects of improvisational music therapy (IMT) on social affect and responsiveness of children with ASD. Design International, multicentre, three-arm, single-masked randomised controlled trial, including a National Institute for Health Research (NIHR)-funded centre that recruited in London and the east of England. Randomisation was via a remote service using permuted blocks, stratified by study site. Setting Schools and private, voluntary and state-funded health-care services. Participants Children aged between 4 and 7 years with a confirmed diagnosis of ASD and a parent or guardian who provided written informed consent. We excluded children with serious sensory disorder and those who had received music therapy within the past 12 months. Interventions All parents and children received enhanced standard care (ESC), which involved three 60-minute sessions of advice and support in addition to treatment as usual. In addition, they were randomised to either one (low-frequency) or three (high-frequency) sessions of IMT per week, or to ESC alone, over 5 months in a ratio of 1 : 1 : 2. Main outcome measures The primary outcome was measured using the social affect score derived from the Autism Diagnostic Observation Schedule (ADOS) at 5 months: higher scores indicated greater impairment. Secondary outcomes included social affect at 12 months and parent-rated social responsiveness at 5 and 12 months (higher scores indicated greater impairment). Results A total of 364 participants were randomised between 2011 and 2015. A total of 182 children were allocated to IMT (90 to high-frequency sessions and 92 to low-frequency sessions), and 182 were allocated to ESC alone. A total of 314 (86.3%) of the total sample were followed up at 5 months [165 (90.7%) in the intervention group and 149 (81.9%) in the control group]. Among those randomised to IMT, 171 (94.0%) received it. From baseline to 5 months, mean scores of ADOS social affect decreased from 14.1 to 13.3 in music therapy and from 13.5 to 12.4 in standard care [mean difference: music therapy vs. standard care = 0.06, 95% confidence interval (CI) –0.70 to 0.81], with no significant difference in improvement. There were also no differences in the parent-rated social responsiveness score, which decreased from 96.0 to 89.2 in the music therapy group and from 96.1 to 93.3 in the standard care group over this period (mean difference: music therapy vs. standard care = –3.32, 95% CI –7.56 to 0.91). There were seven admissions to hospital that were unrelated to the study interventions in the two IMT arms compared with 10 unrelated admissions in the ESC group. Conclusions Adding IMT to the treatment received by children with ASD did not improve social affect or parent-assessed social responsiveness. Future work Other methods for delivering music-focused interventions for children with ASD should be explored. Trial registration Current Controlled Trials ISRCTN78923965. Funding This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 59. See the NIHR Journals Library website for further project information.

Measuring the activity and temperature of rats is commonly required in biomedical research. Conventional approaches necessitate single housing, which affects their behavior and wellbeing. We have used a subcutaneous radiofrequency identification (RFID) transponder to measure ambulatory activity and temperature of individual rats when group-housed in conventional, rack-mounted home cages. The transponder location and temperature is detected by a matrix of antennae in a baseplate under the cage. An infrared high-definition camera acquires side-view video of the cage and also enables automated detection of vertical activity. Validation studies showed that baseplate-derived ambulatory activity correlated well with manual tracking and with side-view whole-cage video pixel movement. This technology enables individual behavioral and temperature data to be acquired continuously from group-housed rats in their familiar, home cage environment. We demonstrate its ability to reliably detect naturally occurring behavioral effects, extending beyond the capabilities of routine observational tests and conventional monitoring equipment. It has numerous potential applications including safety pharmacology, toxicology, circadian biology, disease models and drug discovery.

Introduction We evaluated the feasibility of providing food and water to rodents during whole body plethysmography (WBP) studies as a welfare improvement to standard conditions. Methods Male Han Wistar rats or CD1 mice (n = 8) were placed in WBP chambers and respiratory parameters recorded for approximately 6 h on four separate occasions. On each occasion the animals were exposed to a different plethysmography chamber environment using a randomised design: no food/water (the standard conditions), water bottle, hydrating gel and wet food. In a further session, rats (n = 8) were administered theophylline, or vehicle and respiratory parameters measured in the plethysmography chamber containing wet food. Results Respiratory parameters of rats were not significantly altered by the provision of water or food. Providing wet food resulted in reduced body weight loss. Administration of theophylline caused the expected increase in respiratory rate. When mice were given access to hydrating gel or wet food the respiratory parameters were significantly affected; respiratory rate and tidal volume were increased. Providing wet food resulted in reduced bodyweight loss. Discussion The provision of food and water did not impact on respiratory parameters in rats placed in WBP chambers. When provided with wet food, rats lost less bodyweight. Therefore, to improve welfare conditions for rats during WBP respiratory studies wet food should be provided when appropriate to the study design. In mice, provision of food and water led to changes in respiratory parameters, therefore these improvements in welfare conditions are not suitable for mice.

The safe delivery of hemodialysis (HD) faces dual challenges; the accurate detection of systemic circulatory stress producing cardiovascular (CV) injury, and the ability to enable effective preemptive intervention for such injury. We performed a pilot study to examine the capability of a new noninvasive, real-time monitoring system to detect the deleterious effects of HD on CV stability.Eight patients were evaluated with echocardiography prior to the initiation of HD and again at peak HD stress. Continuous CV physiologic monitoring was performed throughout using oximeter-based pulse waveform analysis (CVInsightA reduction in pulse strength (PS) of ≥40% detected by CVI was associated with the development of RWMA (P = 0.005). This reduction occurred in 6/8 patients, all of whom exhibited myocardial stunning. Two patients had no significant reduction in PS nor evidence of myocardial stunning. In subjects with cardiac stunning, the decrease in PS was evident early during HD, 11.49 ± 10 minutes into HD treatment, prior to the detection of RWMA, which were assessed at peak HD stress, mean 210 ± 16.43 minutes into HD treatment.Percutaneous perfusion monitoring, using pulse wave analysis, appears to be useful in identifying circulatory stress during HD and predicting the development of HD-induced myocardial stunning with a lead time long enough to consider timely intervention.

Oppression is commonly deemed a problem of freedom. How though should we conceptualise the freedom-restricting nature of oppression? This paper aims to show that the unfreedom in oppression may be understood in terms of individual negative liberty. The controversial concept of collective unfreedom is not needed. Non-cooperation among the oppressed generates constraints on individual freedom. This non-cooperation is ultimately attributable to the exercise of social power by oppressors. It is in this sense that the resultant states of individual unfreedom are due relations of oppression.

Nausea and vomiting are components of a complex mechanism that signals food avoidance and protection of the body against the absorption of ingested toxins. This response can also be triggered by pharmaceuticals. Predicting clinical nausea and vomiting liability for pharmaceutical agents based on pre-clinical data can be problematic as no single animal model is a universal predictor. Moreover, efforts to improve models are hampered by the lack of translational animal and human data in the public domain. AZD3514 is a novel, orally-administered compound that inhibits androgen receptor signaling and down-regulates androgen receptor expression. Here we have explored the utility of integrating data from several pre-clinical models to predict nausea and vomiting in the clinic. Single and repeat doses of AZD3514 resulted in emesis, salivation and gastrointestinal disturbances in the dog, and inhibited gastric emptying in rats after a single dose. AZD3514, at clinically relevant exposures, induced dose-responsive "pica" behaviour in rats after single and multiple daily doses, and induced retching and vomiting behaviour in ferrets after a single dose. We compare these data with the clinical manifestation of nausea and vomiting encountered in patients with castration-resistant prostate cancer receiving AZD3514. Our data reveal a striking relationship between the pre-clinical observations described and the experience of nausea and vomiting in the clinic. In conclusion, the emetic nature of AZD3514 was predicted across a range of pre-clinical models, and the approach presented provides a valuable framework for predicition of clinical nausea and vomiting.