Everything Must Go

Thomas Brothers' generous advice and manifold goods helped build, fix and maintain countless artworks and houses in and beyond Archway for ninety-seven years (1917-2014). 'Everything Must Go' was an exhibition of artworks organised by AIR and made by their customers, past and present, to mark the closure of Thomas Brothers, and to say thank you to the brothers and their esteemed Archway institution. The art works were bequeathed to the Thomas family. The works were placed by the artists within a certain moment of the emptying shelves. Over the next three weeks the brothers chose to continue the exhibition. It took various forms as they moved the works around their dwindling stock, eventually placing them all together in the central window

Adolescent Cannabinoid and Nicotine Exposure Differentially Alters Adult Nicotine Self-Administration in Males and Females.

IntroductionDuring adolescence, exposure to nicotine or cannabis independently induces effects on neuromaturation and later cognitive function. However, the potential effect of both drugs under co-use conditions has become of increasing concern given the prevalence of e-cigarettes, legalization of cannabis, and availability of synthetic "spice" cannabinoid agonists.Aims and methodsThe current studies investigated the effects of exposure to a cannabinoid receptor agonist (WIN55,212-2) and/or nicotine over a discrete time period in mid-adolescence on later intravenous nicotine self-administration in adult male and female mice. We further examined whether cannabinoid agonist administration in adulthood would alter nicotine reinforcement, with either acute or chronic pairing across 7 days.ResultsWe found that adult males exhibited increased nicotine self-administration at a lower, rewarding nicotine dose following adolescent cannabinoid exposure, either alone or with nicotine coadministration. In contrast, adult females demonstrated an opposing effect in which adolescent cannabinoid and nicotine coexposure resulted in decreased nicotine intake compared with the nicotine only and control groups. Furthermore, after maintaining nicotine self-administration across sessions, pretreatment with a low dose of the cannabinoid agonist decreased nicotine intake in both male and female control mice, and this lowering effect was evidenced after both acute and chronic treatment. However, the cannabinoid agonist was ineffective in altering nicotine intake in mice previously exposed to nicotine, cannabinoid agonist, or both during adolescence.ConclusionsThese data provide evidence that adolescent drug exposure can alter later nicotine reinforcement in a sex-specific manner and can further modulate the effectiveness of interventions in reducing nicotine intake during adulthood.ImplicationsThese studies demonstrate a significant impact of nicotine, cannabinoids, or coexposure on developmental processes during adolescence. Differential effects were observed within each sex, with opposing results found for cannabinoid exposure on nicotine intake in males and females. Intriguingly, we also evidenced resistance to the lowering effects of a cannabinoid agonist on nicotine intake in adulthood based on adolescent drug exposure. Thus, these findings have important implications for our understanding of the impact of nicotine and cannabinoids (eg, Δ9-tetrahydrocannabinol (THC) and synthetic "spice" cannabinoids) during development, with further implications for the effectiveness of therapeutic interventions based on prior drug exposure in youth

Vitamin C Intravenous Treatment In the Setting of Atrial Fibrillation Ablation: Results From the Randomized, Double-Blinded, Placebo-Controlled CITRIS-AF Pilot Study

BackgroundCatheter ablation is an effective treatment for atrial fibrillation (AF), but high levels of post-procedure inflammation predict adverse clinical events. Ascorbic acid (AA) has shown promise in reducing inflammation but is untested in this population. We sought to test the feasibility, safety, and preliminary effects on inflammatory biomarkers in the CITRIS-AF (Vitamin C Intravenous Treatment In the Setting of Atrial Fibrillation Ablation) pilot study. Methods and ResultsPatients scheduled to undergo AF ablation (N=20) were randomized 1:1 to double-blinded treatment with AA (200 mg/kg divided over 24 hours) or placebo. C-reactive protein and interleukin-6 levels were obtained before the first infusion and repeated at 24 hours and 30 days. Pain levels within 24 hours and early recurrence of AF within 90 days were recorded. Median and interquartile range were aged 63 (56–70) years, 13 (65%) men, and 18 (90%) white. Baseline data were similar between the 2 groups except ejection fraction. Baseline C-reactive protein levels were 2.56 (1.47–5.87) mg/L and similar between groups (P=0.48). Change in C-reactive protein from baseline to 24 hours was +10.79 (+6.56–23.19) mg/L in the placebo group and +3.01 (+0.40–5.43) mg/L in the AA group (P=0.02). Conversely, change in interleukin-6 was numerically higher in the AA group, though not statistically significant (P=0.32). One patient in each arm developed pericarditis; no adverse events related to the infusions were seen. There were no significant differences between aggregated post-procedure pain levels within 24 hours or early recurrence of AF (both P\u3e0.05). ConclusionsHigh-dose AA is safe and well tolerated at the time of AF ablation and may be associated with a blunted rise in C-reactive protein, although consistent findings were not seen in interleukin-6 levels. Further studies are needed to validate these findings and explore the potential benefit in improving clinically relevant outcomes

Predicting the animal hosts of coronaviruses from compositional biases of spike protein and whole genome sequences through machine learning

The COVID-19 pandemic has demonstrated the serious potential for novel zoonotic coronaviruses to emerge and cause major outbreaks. The immediate animal origin of the causative virus, SARS-CoV-2, remains unknown, a notoriously challenging task for emerging disease investigations. Coevolution with hosts leads to specific evolutionary signatures within viral genomes that can inform likely animal origins. We obtained a set of 650 spike protein and 511 whole genome nucleotide sequences from 225 and 187 viruses belonging to the family Coronaviridae , respectively. We then trained random forest models independently on genome composition biases of spike protein and whole genome sequences, including dinucleotide and codon usage biases in order to predict animal host (of nine possible categories, including human). In hold-one-out cross-validation, predictive accuracy on unseen coronaviruses consistently reached ∼73%, indicating evolutionary signal in spike proteins to be just as informative as whole genome sequences. However, different composition biases were informative in each case. Applying optimised random forest models to classify human sequences of MERS-CoV and SARS-CoV revealed evolutionary signatures consistent with their recognised intermediate hosts (camelids, carnivores), while human sequences of SARS-CoV-2 were predicted as having bat hosts (suborder Yinpterochiroptera), supporting bats as the suspected origins of the current pandemic. In addition to phylogeny, variation in genome composition can act as an informative approach to predict emerging virus traits as soon as sequences are available. More widely, this work demonstrates the potential in combining genetic resources with machine learning algorithms to address long-standing challenges in emerging infectious diseases

Increasing access to CBT for psychosis patients: a feasibility, randomised controlled trial evaluating brief, targeted CBT for distressing voices delivered by assistant psychologists (GiVE2)

Background: The National Institute for Health and Care Excellence (NICE) recommends that Cognitive Behaviour Therapy for psychosis (CBTp) is offered to all patients with a psychosis diagnosis. However, only a minority of psychosis patients in England and Wales are offered CBTp. This is attributable, in part, to the resource-intensive nature of CBTp. One response to this problem has been the development of CBTp in brief formats that are targeted at a single symptom and the mechanisms that maintain distress. We have developed a brief form of CBTp for distressing voices and reported preliminary evidence for its effectiveness when delivered by highly trained therapists (clinical psychologists). This study will investigate the delivery of this intervention by a cost-effective workforce of assistant psychologists following a brief training and evaluate the acceptability and feasibility of conducting a future, definitive, randomised controlled trial (RCT). Methods: This is a feasibility study for a pragmatic, three-arm, parallel-group, superiority 1:1:1 RCT comparing a Guided self-help CBT intervention for voices and treatment as usual (GiVE) to Supportive Counselling and treatment as usual (SC) to treatment as usual alone (TAU), recruiting across two sites, with blinded post-treatment and follow-up assessments. A process evaluation will quantitatively and qualitatively explore stakeholder experience. Discussion: Expected outcomes will include an assessment of the feasibility of conducting a definitive RCT, and data to inform the calculation of its sample size. If evidence from a subsequent, fully powered RCT suggests that GiVE is clinically and cost-effective when delivered by briefly trained assistant psychologists, CBTp offered in these less resource-intensive forms has the potential to generate benefits for individual patients (reduced distress, enhanced recovery and enhanced quality of life), service-level patient benefit (increased access to evidence-based psychological therapies) and economic benefits to the NHS (in terms of the reduced use of mental health inpatient services). Trial registration: Current Controlled Trials, ISRCTN registration number: 16166070. Registered on 5 February 2019

An exploration of the impact of working in pairs on the dental clinical learning environment: Students’ views

Introduction: The aims of this study were to explore the undergraduate dental clinical students' experiences and perspectives of paired working in the clinical learning environment. Materials and methods: An interpretivist methodological approach with a socio-cultural lens was used. A stratified purposeful sampling strategy was chosen. Students digitally recorded three audio-diaries using Gibbs' cycle to guide reflection on collabo-rating clinically with a peer. 1:1 semi-structured interviews were held using a topic guide. Inductive thematic data analysis was undertaken.Results: Eight participants were recruited. Main themes related to individual characteristics (motivation, professionalism, knowledge and experience) and relational features (feeling safe, attaching value, positive working relationships) that contributed to effective collaborative partnerships. The social setting is important for learning in the dental clinical environment. Benchmarking is used by students to motivate and reas-sure. Students learnt from their peers, particularly when they felt safe and supported and had developed good relationships. A lesser quality learning experience was high-lighted in the assistant role. Conclusion: Paired working for clinical training was viewed mostly positively. Working with a variety of peers was beneficial and enabled development of interpersonal skills and professionalism. More effective collaborative learning partnerships were de-scribed when students felt they belonged and had affective support. Disadvantages of paired working were noted as reduced hands-on experience, particularly for senior students and when working in the assistant role. Ground rules and setting learning goals to change the mind-set about the assistant role were recommended. Emotional and practical support of students is needed in the clinical setting

Migration Pathways, Behavioural Thermoregulation and Overwintering Grounds of Blue Sharks in the Northwest Atlantic

The blue shark Prionace glauca is the most abundant large pelagic shark in the Atlantic Ocean. Although recaptures of tagged sharks have shown that the species is highly migratory, migration pathways towards the overwintering grounds remain poorly understood. We used archival satellite pop-up tags to track 23 blue sharks over a mean period of 88 days as they departed the coastal waters of North America in the autumn. Within 1–2 days of entering the Gulf Stream (median date of 21 Oct), all sharks initiated a striking diel vertical migration, taking them from a mean nighttime depth of 74 m to a mean depth of 412 m during the day as they appeared to pursue vertically migrating squid and fish prey. Although functionally blind at depth, calculations suggest that there would be a ∼2.5-fold thermoregulatory advantage to swimming and feeding in the markedly cooler deep waters, even if there was any reduced foraging success associated with the extreme depth. Noting that the Gulf Stream current speeds are reduced at depth, we used a detailed circulation model of the North Atlantic to examine the influence of the diving behaviour on the advection experienced by the sharks. However, there was no indication that the shark diving resulted in a significant modification of their net migratory pathway. The relative abundance of deep-diving sharks, swordfish, and sperm whales in the Gulf Stream and adjacent waters suggests that it may serve as a key winter feeding ground for large pelagic predators in the North Atlantic

Public Health Research Implementation and Translation: Evidence from Practice-Based Research Networks

BACKGROUND: Research on how best to deliver efficacious public health strategies in heterogeneous community and organizational contexts remains limited. Such studies require the active engagement of public health practice settings in the design, implementation, and translation of research. Practice-based research networks (PBRNs) provide mechanisms for research engagement, but until now they have not been tested in public health settings. PURPOSE: This study uses data from participants in 14 public health PBRNs and a national comparison group of public health agencies to study processes influencing the engagement of public health settings in research implementation and translation activities. METHODS: A cross-sectional network analysis survey was fielded with participants in public health PBRNs approximately 1 year after network formation (n=357) and with a nationally representative comparison group of U.S. local health departments not participating in PBRNs (n=625). Hierarchic regression models were used to estimate how organizational attributes and PBRN network structures influence engagement in research implementation and translation activities. Data were collected in 2010-2012 and analyzed in 2012. RESULTS: Among PBRN participants, both researchers and practice agencies reported high levels of engagement in research activities. Local public health agencies participating in PBRNs were two to three times more likely than nonparticipating agencies to engage in research implementation and translation activities (p \u3c 0.05). Participants in less densely connected PBRN networks and in more peripheral locations within these networks reported higher levels of research engagement, greater perceived benefits from engagement, and greater likelihood of continued participation. CONCLUSIONS: PBRN networks can serve as effective mechanisms for facilitating research implementation and translation among public health practice settings