The ethics of involving persons with cognitive impairments and/or mental illness in research continues to gain academic and public attention. Concerns about the ability of such persons to provide ethically and legally valid consent and about the appropriateness of their research involvement in certain categories of studies have resulted in publication of guidelines, position papers, standards, and court decisions. These analyses address not only when and from whom informed consent may be obtained but also under what conditions it is ethically permissible to involve persons in research who are too decisionally impaired to provide their own consent.

It is an advance in research ethics that there is heightened appreciation of the need for greater protections for, and possibly research participation limitations on, persons unable to give their own consent. In our zeal to protect potentially vulnerable subjects, however, we must craft new protections carefully. Prudence is required in shaping and implementing any new protections.

Understanding risk factors for death from Covid-19 is key to providing good quality clinical care. We assessed the presenting characteristics of the ‘first wave’ of patients with Covid-19 at Royal Oldham Hospital, UK and undertook logistic regression modelling to investigate factors associated with death. Of 470 patients admitted, 169 (36%) died. The median age was 71 years (interquartile range 57–82), and 255 (54.3%) were men. The most common comorbidities were hypertension (n = 218, 46.4%), diabetes (n = 143, 30.4%) and chronic neurological disease (n = 123, 26.1%). The most frequent complications were acute kidney injury (AKI) (n = 157, 33.4%) and myocardial injury (n = 21, 4.5%). Forty-three (9.1%) patients required intubation and ventilation, and 39 (8.3%) received non-invasive ventilation. Independent risk factors for death were increasing age (odds ratio (OR) per 10 year increase above 40 years 1.87, 95% confidence interval (CI) 1.57–2.27), hypertension (OR 1.72, 95% CI 1.10–2.70), cancer (OR 2.20, 95% CI 1.27–3.81), platelets <150 × 103/μl (OR 1.93, 95% CI 1.13–3.30), C-reactive protein ≥100 μg/ml (OR 1.68, 95% CI 1.05–2.68), >50% chest radiograph infiltrates (OR 2.09, 95% CI 1.16–3.77) and AKI (OR 2.60, 95% CI 1.64–4.13). There was no independent association between death and gender, ethnicity, deprivation level, fever, SpO2/FiO2, lymphopoenia or other comorbidities. These findings will inform clinical and shared decision making, including use of respiratory support and therapeutic agents.

Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.

Recent research has suggested that two linguistic processes are displacing Cockney: the emergence of Multicultural London English (MLE) in inner London and dialect levelling (e.g. Kerswill & Williams 2005). This study investigates firstly whether Cockney phonetic features have ‘moved East’ to Essex (Fox 2015), and secondly the features’ indexicality in relation to place and identity. Fifty-four participants from Debden, an outpost of the Cockney Diaspora, completed a sociolinguistic interview. Vowel measurements were made from a wordlist and passage, and quantitative attitudinal and qualitative data were extracted from a questionnaire and interviews. Overall, changes in identity as a result of social change exceeded linguistic changes, and linguistic labels were not interpreted uniformly across the community. Whilst Cockney variants were largely maintained in young speakers, they were transposed onto an ‘Essex’ accent. Furthermore, some young women but no young men considered themselves Cockney, likely due to the matrifocal nature of Cockney. (Cockney, phonetic variation and change, dialect levelling, identity, indexicality, gender)

Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.

OBJECTIVES/GOALS: Primary graft dysfunction (PGD) is acute lung injury in the first three days after lung transplant. Patients that experience PGD have increased mortality and an increased risk of chronic lung allograft dysfunction. The pathogenesis is thought to be an ischemia-reperfusion injury but is incompletely understood and there are no specific therapies. We investigated the role of the microbiome in PGD and associations with inflammation and markers of aspiration. METHODS/STUDY POPULATION: We collected airway lavage samples from lung transplant donors before procurement and recipients after reperfusion. We extracted DNA, amplified the bacterial 16S rRNA gene, and sequenced on the Illumina MiSeq platform. QIIME2 and Deblur were used for bioinformatic analysis. R packages were used for downstream analysis and visualizations. The host response was quantified using the Milipore 41-plex Luminex and an ELISA for pepsin. Clinical data was collected by the Penn Lung Transplant Outcomes Group. PGD was assessed by degree of hypoxemia and chest X-ray findings in the 72 hours after transplant. RESULTS/ANTICIPATED RESULTS: There was no significant difference in alpha diversity (Shannon index, p = 0.51), biomass (via comparison of 16S amplicon PicoGreen, p = 0.6), or beta diversity (Weighted UniFrac, p = 0.472, PERMANOVA) between subjects with PGD grade 3 (n = 36) and those that did not (n = 96). On taxonomic analysis, we found an enrichment of Prevotella in donor and recipient lungs that went on to develop PGD (p = 0.05). To follow up this finding we measured immune response and pepsin concentrations in recipient lungs. We found elevated levels in 35/41 cytokines measured in subjects that developed PGD as well as an elevation in pepsin and a correlation between pepsin concentration and Prevotella relative abundance (Figure 1). Additionally, Prevotella relative abundance had statistically significant positive correlations with multiple cytokines such as IL-6 (Pearson’s = 0.26, p = 0.009) and eotaxin (Pearson’s = 0.24, p = 0.016). DISCUSSION/SIGNIFICANCE OF IMPACT: There is an enrichment of oral anerobes in lung allografts that eventually develop PGD. This is associated with elevated levels of pepsin and markers of inflammation. These lines of evidence suggest aspiration contributes to priming the allograft for PGD.

Stigma against mental illness and the mentally ill is well known. However, stigma against psychiatrists and mental health professionals is known but not discussed widely. Public attitudes and also those of other professionals affect recruitment into psychiatry and mental health services. The reasons for this discriminatory attitude are many and often not dissimilar to those held against mentally ill individuals. In this Guidance paper we present some of the factors affecting the image of psychiatry and psychiatrists which is perceived by the public at large. We look at the portrayal of psychiatry, psychiatrists in the media and literature which may affect attitudes. We also explore potential causes and explanations and propose some strategies in dealing with negative attitudes. Reduction in negative attitudes will improve recruitment and retention in psychiatry. We recommend that national psychiatric societies and other stakeholders, including patients, their families and carers, have a major and significant role to play in dealing with stigma, discrimination and prejudice against psychiatry and psychiatrists.

Stigma and social exclusion related to mental health are of substantial public health importance for Europe. As part of ROAMER (ROAdmap for MEntal health Research in Europe), we used systematic mapping techniques to describe the current state of research on stigma and social exclusion across Europe. Findings demonstrate growing interest in this field between 2007 and 2012. Most studies were descriptive (60%), focused on adults of working age (60%) and were performed in Northwest Europe—primarily in the UK (32%), Finland (8%), Sweden (8%) and Germany (7%). In terms of mental health characteristics, the largest proportion of studies investigated general mental health (20%), common mental disorders (16%), schizophrenia (16%) or depression (14%). There is a paucity of research looking at mechanisms to reduce stigma and promote social inclusion, or at factors that might promote resilience or protect against stigma/social exclusion across the life course. Evidence is also limited in relation to evaluations of interventions. Increasing incentives for cross-country research collaborations, especially with new EU Member States and collaboration across European professional organizations and disciplines, could improve understanding of the range of underpinning social and cultural factors which promote inclusion or contribute toward lower levels of stigma, especially during times of hardship.

The unprecedented growth, availability and accessibility of sophisticated image analysis algorithms and powerful computational resources led to the idea of developing web-based computational infrastructures that could meet users’ new requirements. On the other hand the gap between the pace of data generation and the capability to extract clinically or scientifically relevant information is rapidly widening.

Integration of the power of sophisticated mathematical models, efficient computational algorithms and advanced hardware infrastructure provides the necessary sensitivity to detect, extract and analyze subtle, dynamic and distributed patterns distinguishing one brain from another, and a diseased brain from a normal brain.

neuGRID is the leading e-Infrastructure where neuroscientists can find core services and resources for brain image analysis. The neuGRID platform makes use of grid services and computing, and was developed with the final aim of overcoming the hurdles that the average scientist meets when trying to set up advanced experiments in computational neuroimaging, thereby empowering a larger base of scientists. Although originally built for neuroscientists working in the field of AD, the infrastructure is designed to be expandable to services from other medical fields (e.g. multiple sclerosis, psychiatric conditions).

“neuGRID for Users” will provide an e-Science environment by further developing and deploying the neuGRID infrastructure to deliver a Virtual Laboratory offering neuroscientists access to a wide range of datasets and algorithm pipelines, access to computational resources, services, and support. Information from this abstract is intended to make aware researchers working with neuroimaging of all possibilities when it comes to resources.