Tonic inhibition of accumbal spiny neurons by extrasynaptic 4 GABAA receptors modulates the actions of psychostimulants

Within the nucleus accumbens (NAc), synaptic GABAA receptors (GABAARs) mediate phasic inhibition of medium spiny neurons (MSNs) and influence behavioral responses to cocaine. We demonstrate that both dopamine D1- and D2-receptor-expressing MSNs (D-MSNs) additionally harbor extrasynaptic GABAARs incorporating α4, β, and δ subunits that mediate tonic inhibition, thereby influencing neuronal excitability. Both the selective δ-GABAAR agonist THIP and DS2, a selective positive allosteric modulator, greatly increased the tonic current of all MSNs from wild-type (WT), but not from δ−/− or α4−/− mice. Coupling dopamine and tonic inhibition, the acute activation of D1 receptors (by a selective agonist or indirectly by amphetamine) greatly enhanced tonic inhibition in D1-MSNs but not D2-MSNs. In contrast, prolonged D2 receptor activation modestly reduced the tonic conductance of D2-MSNs. Behaviorally, WT and constitutive α4−/− mice did not differ in their expression of cocaine-conditioned place preference (CPP). Importantly, however, mice with the α4 deletion specific to D1-expressing neurons (α4D1−/−) showed increased CPP. Furthermore, THIP administered systemically or directly into the NAc of WT, but not α4−/− or α4D1−/− mice, blocked cocaine enhancement of CPP. In comparison, α4D2−/− mice exhibited normal CPP, but no cocaine enhancement. In conclusion, dopamine modulation of GABAergic tonic inhibition of D1- and D2-MSNs provides an intrinsic mechanism to differentially affect their excitability in response to psychostimulants and thereby influence their ability to potentiate conditioned reward. Therefore, α4βδ GABAARs may represent a viable target for the development of novel therapeutics to better understand and influence addictive behaviors

Understanding the causes of local disputes in paediatrics to develop pathways to dispute resolution in North East Scotland. [RCPCH Poster]

Conflicts over the care of children with life-limiting conditions can reach the point where courts have to intervene,but giving evidence causes distress, unwanted media attention and costs. The decision in Charlie Gard’s case in Englandincluded a plea for parties to mediate. No case has arisen in Scotland, where law and practice differ, but there are approximately 16,000 children with complex conditions where care might potentially be disputed. This study seeks to understand reasons for disputes, identify potential solutions (including mediation) and reduce the risk of a case coming before a Scottish court. In-depth interviews (online and face-to-face) with NHS Grampian clinicians and parents were conducted from which qualitative data were obtained on their experiences and views on disagreements about care, how decision-making is handled, what works well and what might improve existing approaches. This is being funded by the NHS Grampian Endowment Fund. Ten clinicians and five parents were interviewed. Preliminary thematic analysis suggests that clinicians feel multidisciplinary team meetings improve conflict resolution for patients with complex requirements, where specialism boundaries can blur. When disputes arise, the type of intervention varied depending on its scale, urgency and impact on other care teams. A cause of disputes is variation in goals within and between care teams, but micro-discussions and step-bystep approaches from the outset work well and mitigate risk of disputes. The settings, timing and language used in conversations with parents is important. Findings suggest that clinicians may prefer a two-stage process where meetings are held without parents in the first instance. A strong Chair facilitates useful meetings, but parents still find it difficult to know who to address questions to. Families' use of social media/online searches can be problematic and lead to strained relationships, but emphasis on 'good death' and 'doing what's right' were highlighted. When a child is hospitalised, 'handing over' a child who has been looked after at home can be difficult for parents and home care teams. A desire to connect with parents facing similar challenges was expressed. It is clear that conflict exists in Scottish paediatric care. Practice suggests that there are strategies which can be employed to minimise risk of intractable disputes arising which could be used to assess the suitability of mediation and formalised into a toolkit to support families and clinicians

Understanding the causes of local disputes in paediatrics to develop pathways to dispute resolution in North East Scotland. [NHS Grampian R&D Poster]

Conflicts between parents and clinicians over the care of children with life-limiting conditions can reach the point where courts must intervene, causing distress, unwanted media attention and costs. This NHS Grampian case study sought to understand reasons for disputes, identify potential solutions and reduce the risk of a case coming before a Scottish court. In-depth semi-structured interviews with 20 participants (a mix of NHS Grampian clinicians and parents) were conducted from which qualitative data were obtained on their experiences of and views on disagreements about care, how decision-making is handled, what works well and what might improve existing approaches

Nurse practitioner administered point-of-care ultrasound compared with X-ray for children with clinically non-angulated distal forearm fractures in the ED: A diagnostic study

Paediatric distal forearm fractures are a common ED presentation. They can be diagnosed with point-of-care ultrasound (POCUS) as an alternative to X-rays. Given that ED nurse practitioners (NPs) are relied on for the diagnosis of paediatric fractures, it is important to describe the diagnostic accuracy of NP-conducted POCUS versus X-ray.This prospective diagnostic study was conducted in a tertiary paediatric hospital in Queensland, Australia, between February 2018 and April 2019. Participants were children aged 4-16 years with a clinically non-angulated, suspected distal forearm fracture. Diagnosis from 6-view NP-administered POCUS of the distal radius and ulna was compared against the reference standard of 2-view X-ray. Each patient received both imaging modalities. Overall forearm diagnosis was classified as 'no', 'buckle' or 'other' fracture for both modalities. The primary outcome was diagnostic accuracy for 'any' fracture ('buckle' and 'other' fractures combined). Secondary outcomes included diagnostic accuracy for 'other' fractures versus 'buckle' and 'no' fractures combined, and pain, imaging duration and preference for modality.Of 204 recruited patients, 129 had X-ray-diagnosed forearm fractures. The sensitivity and specificity for NP-administered POCUS were 94.6% (95% CI 89.2% to 97.3%) and 85.3% (95% CI 75.6% to 91.6%), respectively. 'Other' fractures (mostly cortical breach fractures), when compared with 'buckle'/ 'no' fractures, had sensitivity 81.0% (95% CI 69.1% to 89.1%) and specificity 95.9% (95% CI 91.3% to 98.1%). Pain and imaging duration were clinically similar between modalities. There was a preference for POCUS by patients, parents and NPs.NP-administered POCUS had clinically acceptable diagnostic accuracy for paediatric patients presenting with non-angulated distal forearm injuries. This included good sensitivity for diagnosis of 'any' fracture and good specificity for diagnosis of cortical breach fractures alone. Given the preference for POCUS, and the lack of difference in pain and duration between modalities, future research should consider functional outcomes comparing POCUS with X-ray in this population in a randomised controlled trial

Economic evidence for the prevention and treatment of atopic eczema: a protocol for a systematic review

Background: Eczema, synonymous with atopic eczema or atopic dermatitis, is a chronic skin disease that has a similar impact on health-related quality of life as other chronic diseases. The proposed research aims to provide a comprehensive systematic assessment of the economic evidence base available to inform economic modelling and decision making on interventions to prevent and treat eczema at any stage of the life course. Whilst the Global Resource of Eczema Trials (GREAT) database collects together the effectiveness evidence for eczema there is currently no such systematic resource on the economics of eczema. It is important to gain an overview of the current state of the art of economic methods in the field of eczema in order to strengthen the economic evidence base further. Methods/design: The proposed study is a systematic review of the economic evidence surrounding interventions for the prevention and treatment of eczema. Relevant search terms will be used to search MEDLINE, EMBASE, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, Health Technology Assessment, Cumulative Index to Nursing and Allied Health Literature, Econ Lit, Scopus, Cost-Effectiveness Analysis Registry and Web of Science in order to identify relevant evidence. To be eligible for inclusion studies will be primary empirical studies evaluating the cost, utility or full economic evaluation of interventions for preventing or treating eczema. Two reviewers will independently assess studies for eligibility and perform data abstraction. Evidence tables will be produced presenting details of study characteristics, costing methods, outcome methods and quality assessment. The methodological quality of studies will be assessed using accepted checklists. Discussion: The systematic review is being undertaken to identify the type of economic evidence available, summarise the results of the available economic evidence and critically appraise the quality of economic evidence currently available to inform future economic modelling and resource allocation decisions about interventions to prevent or treat eczema. We aim to use the review to offer guidance about how to gather economic evidence in studies of eczema and/or what further research is necessary in order to inform this

Cryptocarbon: the promises and pitfalls of forest protection on a blockchain

In this commentary, we explore how blockchain is being leveraged to address the fundamental problems with market-based forest protection globally. In doing so, we consider the ways ‘cryptocarbon’ initiatives are creating new challenges that have so far escaped critical scrutiny. A blockchain is a distributed and immutable electronic database – a ledger of every transaction that has ever taken place on a network, stored as cryptographically secured blocks, strung together in a chain. The technology is being increasingly hyped as applicable for a whole range of industries, social service provisions, and environmental management concerns. This includes the facilitation of natural asset market mechanisms, like Reducing Emissions from Deforestation and Forest Degradation (REDD+). The original aim of REDD+ was to incentivise conservation, making tropical forests more valuable standing than cut down. Multiple factors, including lack of consumer interest, created an oversupply of carbon commodities. Ninety-five percent of the world’s avoided deforestation credits, representing millions of hectares of conserved forest, were stuck without a buyer. Several flagging REDD+ projects are now hoping that blockchain technology can carry them to new heights of market capitalisation. However, like with any powerful new technology, the benefits remain ambiguous

Unusual features in the nonlinear microwave surface impedance of Y-Ba-Cu-O thin films

Striking features have been found in the nonlinear microwave (8 GHz) surface impedance $Z_s=R_s + jX_s$ of high-quality YBaCuO thin films with comparable low power characteristics [$R_{res}\sim 35--60 \mu\Omega$ and $\lambda_L(15 K)\sim 130--260 nm$]. The surface resistance $R_s$ is found to increase, decrease, or remain independent of the microwave field $H_{rf}$ (up to 60 mT) at different temperatures and for different samples. However, the surface reactance $X_s$ always follows the same functional form. Mechanisms which may be responsible for the observed variations in $R_s$ and $X_s$ are briefly discussed.Comment: 4 pages, 4 figure

Genome-wide association studies for feedlot and growth traits in cattle

A genome wide-association study for production traits in cattle was carried out using genotype data from the 10K Affymetrix (Santa Clara, CA) and the 50K Illumina (San Diego, CA) SNP chips. The results for residual feed intake (RFI), BW, and hip height in 3 beef breed types (Bos indicus, Bos taurus, and B. indicus × B. taurus), and for stature in dairy cattle, are presented. The aims were to discover SNP associated with all traits studied, but especially RFI, and further to test the consistency of SNP effects across different cattle populations and breed types. The data were analyzed within data sets and within breed types by using a mixed model and fitting 1 SNP at a time. In each case, the number of significant SNP was more than expected by chance alone. A total of 75 SNP from the reference population with 50K chip data were significant (P < 0.001) for RFI, with a false discovery rate of 68%. These 75 SNP were mapped on 24 different BTA. Of the 75 SNP, the 9 most significant SNP were detected on BTA 3, 5, 7, and 8, with P ≤ 6.0 × 10 . In a population of Angus cattle divergently selected for high and low RFI and 10K chip data, 111 SNP were significantly (P < 0.001) associated with RFI, with a false discovery rate of 7%. Approximately 103 of these SNP were therefore likely to represent true positives. Because of the small number of SNP common to both the 10K and 50K SNP chips, only 27 SNP were significantly (P < 0.05) associated with RFI in the 2 populations. However, other chromosome regions were found that contained SNP significantly associated with RFI in both data sets, although no SNP within the region showed a consistent effect on RFI. The SNP effects were consistent between data sets only when estimated within the same breed type

The changing of the guard: groupwork with people who have intellectual disabilities

This paper considers the impact of service systems on group activities. It describes an inter-professional groupwork project facilitated by a social worker and a community nurse. The project provided an emancipatory experience for a group of adults who had intellectual disabilities. The group was charged with the task of reviewing and updating the recruitment and interview processes used by a 'Learning Disability Partnership Board', when employing new support workers. The paper begins with a brief history of intellectual disability and provides a context to the underpinning philosophical belief that people should be encouraged and supported to inhabit valued social roles no matter what disability they may have. It then identifies the ways in which the sponsoring health, education and social care services impacted on the creation and development of a groupwork project. It might have been expected that the nature of the intellectual disability would have been the major influence on group process. However the paper reveals that organisational constraints had a significant impact on group functioning. Issues including, staffing budgets and transport contracts impacted on group process and function. The results of the project show how, with adequate support, people with intellectual disability can make important decisions that have long-reaching impacts on the services