Portable Sensory Room for the West Orange County Consortium for Special Education

This report discusses the development of a Portable Sensory Room to be used at Newland Elementary School in Huntington Beach. Newland Elementary has an exceptional Special Needs program that teaches the children with the most severe cases of autism in its school district. People with autism typically also have sensory processing disorders, which can be extremely disruptive for a child’s development and can make it difficult for a child to be able to concentrate long enough to gain necessary life skills. The idea behind a Sensory Rooms is to create a place to calm the students and to expose them to new stimuli to explore and learn in a calm and non-threatening environment. There are three different Special Needs classrooms that the Portable Sensory Room will be moved between in a single day. The teachers at Newland Elementary also desired a swing element and a pressure applying device. Both of these components are used regularly in Occupational Therapy with children with autism and have been proven to help children develop necessary skills in life. The design of the Portable Sensory Room, which was composed of several brainstorming sessions and decision matrices, lasted several months from Fall 2015 to midway through the Winter 2016 quarter. The final design consists of seven different components - five of the components act as the structure of the room and can easily connect to one another to achieve a uniform enclosure and two are separate from the room structure. All of these components have interactions on their faces that either comfort or challenge the children and all contribute to a calming sea theme throughout. The components are all on locking casters which makes transportation of the assembly easy. The five components of the room structure are: the tactile wall, the bookshelf, the tactile station, the fabric panels, and the LED panels. The tactile wall focuses on helping the children gain fine motor skills by use of tracks that the children can move fish along, a moveable gear set, and a whiteboard. The bookshelf is filled with activities for fine motor skills as well, and provides extra storage for the teachers to arrange according to their desires. The tactile station is a dresser with calming light effects at the top. The drawers can be completely removed and put on the floor, where the children can play with tactile interactions in an enclosed space to avoid a mess. The fabric panels provide tactile sensations using several swatches of fabric that range from calming to challenging. The LED panels have a calming ocean mural and also allow children to observe the notion of cause-and-effect via a control box that changes the light display. The other two components are the swing structure and the pressure applicator, which can either be used in the room or separately from the room depending on the teachers’ preferences. The swing structure was purchased from Amazon and allows for a 360 degree rotation. The pressure applicator was built by the team and is comprised of two horizontal rollers that the child can slide in between. The addition of rubber bands allows the child/teacher to choose how much pressure will be exerted on the child. The build phase of the project lasted from the end of Winter 2016 quarter to the end of Spring 2016 quarter. All of the components were made from lumber and sanded down in order to avoid any sharp edges. Testing was performed to verify that the teachers would not have to exert an enormous effort to move all of the components, as well as to determine the tipping loads for each of the components. The tipping loads were below the desired specification; in order to mitigate this, two adults will be required to move each component. When the room is assembled together, the entire structure is quite stable and does not pose a tipping hazard. The final product will be delivered to Newland Elementary School on June 17th, 2016

MEDREV (pharmacy-health psychology intervention in people living with dementia with behaviour that challenges):the feasibility of measuring clinical outcomes and costs of the intervention

BACKGROUND: People living with dementia in care homes frequently exhibit "behaviour that challenges". Anti-psychotics are used to treat such behaviour, but are associated with significant morbidity. This study researched the feasibility of conducting a trial of a full clinical medication review for care home residents with behaviour that challenges, combined with staff training. This paper focusses on the feasibility of measuring clinical outcomes and intervention costs. METHODS: People living with moderate to severe dementia, receiving psychotropics for behaviour that challenges, in care homes were recruited for a medication review by a specialist pharmacist. Care home and primary care staff received training on the management of challenging behaviour. Data were collected at 8 weeks, and 3 and 6 months. Measures were Neuropsychiatric Inventory-Nursing Home version (NPI-NH), cognition (sMMSE), quality of life (EQ-5D-5 L/DEMQoL) and costs (Client Services Receipt Inventory). Response rates, for clinical, quality of life and health economic measures, including the levels of resource-use associated with the medication review and other non-intervention costs were calculated. RESULTS: Twenty-nine of 34 participants recruited received a medication review. It was feasible to measure the effects of the complex intervention on the management of behaviour that challenges with the NPI-NH. There was valid NPI-NH data at each time point (response rate = 100%). The sMMSE response rate was 18.2%. Levels of resource-use associated with the medication review were estimated for all 29 participants who received a medication review. Good response levels were achieved for other non-intervention costs (100% completion rate), and the EQ-5D-5 L and DEMQoL (≥88% at each of the time points where data was collected). CONCLUSIONS: It is feasible to measure the clinical and cost effectiveness of a complex intervention for behaviour that challenges using the NPI-NH and quality of life measures. TRIAL REGISTRATION: ISRCTN58330068. Retrospectively registered, 15 October 2017

Pulmonary rehabilitation referral and uptake from primary care for people living with COPD: a mixed-methods study.

Healthcare service and patient barriers contribute to low referral to and uptake of pulmonary rehabilitation (PR). Solutions should support skilled clinician-patient conversations and span primary care-PR boundaries to prevent disjointed working. http://bit.ly/2PVKHZf

Natural killer cell responses during SARS-CoV-2 infection and vaccination in people living with HIV-1

Natural killer (NK) cell subsets with adaptive properties are emerging as regulators of vaccine-induced T and B cell responses and are specialized towards antibody-dependent functions contributing to SARS-CoV-2 control. Although HIV-1 infection is known to affect the NK cell pool, the additional impact of SARS-CoV-2 infection and/or vaccination on NK cell responses in people living with HIV (PLWH) has remained unexplored. Our data show that SARS-CoV-2 infection skews NK cells towards a more differentiated/adaptive CD57+FcεRIγ- phenotype in PLWH. A similar subset was induced following vaccination in SARS-CoV-2 naïve PLWH in addition to a CD56bright population with cytotoxic potential. Antibody-dependent NK cell function showed robust and durable responses to Spike up to 148 days post-infection, with responses enriched in adaptive NK cells. NK cell responses were further boosted by the first vaccine dose in SARS-CoV-2 exposed individuals and peaked after the second dose in SARS-CoV-2 naïve PLWH. The presence of adaptive NK cells associated with the magnitude of cellular and humoral responses. These data suggest that features of adaptive NK cells can be effectively engaged to complement and boost vaccine-induced adaptive immunity in potentially more vulnerable groups such as PLWH

A large-scale genome-wide association study meta-analysis of cannabis use disorder

BACKGROUND: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50-70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. METHODS: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. FINDINGS: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07-1·15, p=1·84 × 10 INTERPRETATION: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. FUNDING: National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences

Cognitive control in infancy: attentional predictors using a tablet-based measure

Cognitive control is a predictor of later-life outcomes and may underpin higher order executive processes. The present study examines the development of early cognitive control during the first 24-months. We evaluated a tablet-based assessment of cognitive control among infants aged 18- and 24-months. We also examined concurrent and longitudinal associations between attentional disengagement, general cognitive skills and cognitive control. Participants (N=60, 30 female) completed the tablet-task at 18- and 24-months of age. Attentional disengagement and general cognitive development were assessed at 5-, 8-, 12-, 18- and 24-months using an eye-tracking measure and the Mullen Scales of Early Learning (MSEL), respectively. The cognitive control task demonstrated good internal consistency, sensitivity to age-related change in performance and stable individual differences. No associations were found between infant cognitive control and MSEL scores longitudinally or concurrently. The eye-tracking task revealed that slower attentional disengagement at 8-months, but faster disengagement at 18-months, predicted higher cognitive control scores at 24-months. This task may represent a useful tool for measuring emergent cognitive control. The multifaceted relationship between attention and infant cognitive control suggests that the rapid development of the attentional system in infancy results in distinct attentional skills, at different ages, being relevant for cognitive control development

The Relationship between Therapeutic Alliance and Service User Satisfaction in Mental Health Inpatient Wards and Crisis House Alternatives: A Cross-Sectional Study

Background Poor service user experiences are often reported on mental health inpatient wards. Crisis houses are an alternative, but evidence is limited. This paper investigates therapeutic alliances in acute wards and crisis houses, exploring how far stronger therapeutic alliance may underlie greater client satisfaction in crisis houses. Methods and Findings Mixed methods were used. In the quantitative component, 108 crisis house and 247 acute ward service users responded to measures of satisfaction, therapeutic relationships, informal peer support, recovery and negative events experienced during the admission. Linear regressions were conducted to estimate the association between service setting and measures, and to model the factors associated with satisfaction. Qualitative interviews exploring therapeutic alliances were conducted with service users and staff in each setting and analysed thematically. Results We found that therapeutic alliances, service user satisfaction and informal peer support were greater in crisis houses than on acute wards, whilst self-rated recovery and numbers of negative events were lower. Adjusted multivariable analyses suggest that therapeutic relationships, informal peer support and negative experiences related to staff may be important factors in accounting for greater satisfaction in crisis houses. Qualitative results suggest factors that influence therapeutic alliances include service user perceptions of basic human qualities such as kindness and empathy in staff and, at service level, the extent of loss of liberty and autonomy. Conclusions and Implications We found that service users experience better therapeutic relationships and higher satisfaction in crisis houses compared to acute wards, although we cannot exclude the possibility that differences in service user characteristics contribute to this. This finding provides some support for the expansion of crisis house provision. Further research is needed to investigate why acute ward service users experience a lack of compassion and humanity from ward staff and how this could be changed

Therapeutic gene editing of T cells to correct CTLA-4 insufficiency

Heterozygous mutations in CTLA-4 result in an inborn error of immunity with an autoimmune and frequently severe clinical phenotype. Autologous T cell gene therapy may offer a cure without the immunological complications of allogeneic hematopoietic stem cell transplantation. Here, we designed a homology-directed repair (HDR) gene editing strategy that inserts the CTLA-4 cDNA into the first intron of the CTLA-4 genomic locus in primary human T cells. This resulted in regulated expression of CTLA-4 in CD4+ T cells, and functional studies demonstrated CD80 and CD86 transendocytosis. Gene editing of T cells isolated from three patients with CTLA-4 insufficiency also restored CTLA-4 protein expression and rescued transendocytosis of CD80 and CD86 in vitro. Last, gene-corrected T cells from CTLA-4-/- mice engrafted and prevented lymphoproliferation in an in vivo murine model of CTLA-4 insufficiency. These results demonstrate the feasibility of a therapeutic approach using T cell gene therapy for CTLA-4 insufficiency

Consensus Statement on Public Involvement and Engagement with Data-Intensive Health Research.

This consensus statement reflects the deliberations of an international group of stakeholders with a range of expertise in public involvement and engagement (PI&E) relating to data-intensive health research. It sets out eight key principles to establish a secure role for PI&E in and with the research community internationally and ensure best practice in its execution. Our aim is to promote culture change and societal benefits through ensuring a socially responsible trajectory for innovations in this field.Peer reviewe