Use of functional near-infrared spectroscopy to evaluate cognitive change when using healthcare simulation tools

This is an accepted manuscript of an article published by BMJ on 01/11/2020, available online: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8936993/ The accepted version of the publication may differ from the final published version.Background The use of brain imaging techniques in healthcare simulation is relatively rare. However, the use of mobile, wireless technique, such as functional nearinfrared spectroscopy (fNIRS), is becoming a useful tool for assessing the unique demands of simulation learning. For this study, this imaging technique was used to evaluate cognitive load during simulation learning events. Methods This study took place in relation to six simulation activities, paired for similarity, and evaluated comparative cognitive change between the three task pairs. The three paired tasks were: receiving a (1) face-toface and (2) video patient handover; observing a simulated scene in (1) two dimensions and (2) 360° field of vision; and on a simulated patient (1) taking a pulse and (2) taking a pulse and respiratory rate simultaneously. The total number of participants was n=12. Results In this study, fNIRS was sensitive to variations in task difficulty in common simulation tools and scenarios, showing an increase in oxygenated haemoglobin concentration and a decrease in deoxygenated haemoglobin concentration, as tasks increased in cognitive load. Conclusion Overall, findings confirmed the usefulness of neurohaemoglobin concentration markers as an evaluation tool of cognitive change in healthcare simulation. Study findings suggested that cognitive load increases in more complex cognitive tasks in simulation learning events. Task performance that increased in complexity therefore affected cognitive markers, with increase in mental effort required

Disability, relative poverty and gender : how men with learning disabilities perceive and experience the impact of social divisions on their health

This thesis explores how men with mild to moderate learning disabilities perceive and experience how disability, relative poverty and gender impact on their health. Its theoretical framework grounded in analysis of these social divisions, and informed by the men’s own accounts - previously neglected in research, reveals complex challenges affecting their health on a daily basis. Consistent with the thesis’ overarching perspective, key elements of a participatory approach were adopted in the fieldwork to ensure men with learning disabilities’ active research involvement. They comprised the steering group, and twenty men participated in qualitative interviews facilitated by accessible materials and detailed preliminary preparations. The findings showed the men were aware of health issues, but were grappling with the adverse health effects of impairment, including disabilist health care and victimisation. Low income associated with limited employment confined most men to relative poverty with negative effects on health. The findings demonstrated a sharp appreciation of masculinity. Marginalised by other men, they experienced health threatening abuse, but their resistance to conventional male disregard for health care, had positive implications for their health. The thesis provides a more informed, nuanced understanding of the adverse impact of different dimensions of social disadvantage on the health of men with mild to moderate learning disabilities. In doing so, it demonstrates the value of developing knowledge grounded in their perspectives and experience

A divergent heritage for complex organics in Isheyevo lithic clasts

Primitive meteorites are samples of asteroidal bodies that contain a high proportion of chemically complex organic matter (COM) including prebiotic molecules such as amino acids, which are thought to have been delivered to Earth via impacts during the early history of the Solar System. Thus, understanding the origin of COM, including their formation pathway(s) and environment(s), is critical to elucidate the origin of life on Earth as well as assessing the potential habitability of exoplanetary systems. The Isheyevo CH/CBb carbonaceous chondrite contains chondritic lithic clasts with variable enrichments in 15N believed to be of outer Solar System origin. Using transmission electron microscopy (TEM-EELS) and in situ isotope analyses (SIMS and NanoSIMS), we report on the structure of the organic matter as well as the bulk H and N isotope composition of Isheyevo lithic clasts. These data are complemented by electron microprobe analyses of the clast mineral chemistry and bulk Mg and Cr isotopes obtained by inductively coupled plasma and thermal ionization mass spectrometry, respectively (MC-ICPMS and TIMS). Weakly hydrated (A) clasts largely consist of Mg-rich anhydrous silicates with local hydrated veins composed of phyllosilicates, magnetite and globular and diffuse organic matter. Extensively hydrated clasts (H) are thoroughly hydrated and contain Fe-sulfides, sometimes clustered with organic matter, as well as magnetite and carbonates embedded in a phyllosilicate matrix. The A-clasts are characterized by a more 15N-rich bulk nitrogen isotope composition (δ15N = 200–650‰) relative to H-clasts (δ15N = 50–180‰) and contain extremely 15N-rich domains with δ15N 15N-rich domains show that the lithic clast diffuse organic matter is typically more 15N-rich than globular organic matter. The correlated δ15N values and C/N ratios of nanoglobules require the existence of multiple organic components, in agreement with the H isotope data. The combined H and N isotope data suggest that the organic precursors of the lithic clasts are defined by an extremely 15N-poor (similar to solar) and D-rich component for H-clasts, and a moderately 15N-rich and D-rich component for A-clasts. In contrast, the composition of the putative fluids is inferred to include D-poor but moderately to extremely 15N-rich H- and N-bearing components. The variable 15N enrichments in H- and A-clasts are associated with structural differences in the N bonding environments of their diffuse organic matter, which are dominated by amine groups in H-clasts and nitrile functional groups in A-clasts. We suggest that the isotopically divergent organic precursors in Isheyevo clasts may be similar to organic moieties in carbonaceous chondrites (CI, CM, CR) and thermally recalcitrant organic compounds in ordinary chondrites, respectively. The altering fluids, which are inferred to cause the 15N enrichments observed in the clasts, may be the result of accretion of variable abundances of NH3 and HCN ices. Finally, using bulk Mg and Cr isotope composition of clasts, we speculate on the accretion regions of the various primitive chondrites and components and the origin of the Solar System’s N and H isotope variability

A randomised controlled trial to evaluate the impact of indoor living space on dairy cow production, reproduction and behaviour

As a global society, we have a duty to provide suitable care and conditions for farmed livestock to protect animal welfare and ensure the sustainability of our food supply. The suitability and biological impacts of housing conditions for intensively farmed animals is a complex and emotive subject, yet poorly researched, meaning quantitative evidence to inform policy and legislation is lacking. Most dairy cows globally are housed for some duration during the year, largely when climatic conditions are unfavourable. However, the impact on biology, productivity and welfare of even the most basic housing requirement, the quantity of living space, remains unknown. We conducted a long-term (1-year), randomised controlled trial (CONSORT 10 guidelines) to investigate the impact of increased living space (6.5m2 vs 3m2 per animal) on critical aspects of cow biology, behaviour and productivity. Adult Holstein dairy cows (n = 150) were continuously and randomly allocated to a high or control living space group with all other aspects of housing remaining identical between groups. Compared to cows in the control living space group, cows with increased space produced more milk per 305d lactation (primiparous: 12,235L vs 11,592L, P < 0.01; multiparous: 14,746L vs 14,644L, P < 0.01) but took longer to become pregnant after calving (primiparous: 155d vs 83d, P = 0.025; multiparous: 133d vs 109d). In terms of behaviour, cows with more living space spent significantly more time in lying areas (65min/d difference; high space group: 12.43h/day, 95% CI = 11.70-13.29; control space group: 11.42h/day, 95% CI = 10.73-12.12) and significantly less time in passageways (64min/d), suggesting enhanced welfare when more space was provided. A key physiological difference between groups was that cows with more space spent longer ruminating each day. This is the first long term study in dairy cows to demonstrate that increased living space results in meaningful benefits in terms of productivity and behaviour and suggests that the interplay between farmed animals and their housed environment plays an important role in the concepts of welfare and sustainability of dairy farming

Identification of novel CD8+ T cell epitopes in human herpesvirus 6B U11 and U90

Human herpesvirus 6B (HHV6B) infects over 90% of the population, and normally establishes a latent infection, where episodes of reactivation are asymptomatic. However, in immunocompromised patients HHV6B reactivation is associated with high morbidity and mortality. Cellular immunotherapy has been utilised against other herpesvirus in immunocompromised settings. However, limited information on the immune response against HHV6B has hampered the development of immunotherapy for HHV6B-driven disease. In this study we have analysed the cellular immune response against four HHV6B antigens in a panel of 30 healthy donors. We show that the base-line level of T cell reactivity in peripheral blood is very low to undetectable. A short-term reactivation step enabled expansion of T cell responses, and all donors responded to at least 1 antigen, but more commonly 3 or 4. A hierarchy of immunogenicity was determined with antigens U90 and U54 being co-dominant, followed by U11 and U39. Putative CD8+ T cell epitopes were mapped to U90 and U11, predicted to be presented in the context of HLA-A1, A29, B39 and C6. T cells reactive against these novel epitopes were able to recognise virus-infected cells. Our data is supportive of the application and on-going development of T cell immunotherapy against HHV6B-driven disease in the immunocompromised host

The applied development of a tiered multilocus sequence typing (MLST) scheme for Dichelobacter nodosus

Dichelobacter nodosus (D. nodosus) is the causative pathogen of ovine footrot, a disease that has a significant welfare and financial impact on the global sheep industry. Previous studies into the phylogenetics of D. nodosus have focused on Australia and Scandinavia, meaning the current diversity in the United Kingdom (U.K.) population and its relationship globally, is poorly understood. Numerous epidemiological methods are available for bacterial typing; however, few account for whole genome diversity or provide the opportunity for future application of new computational techniques. Multilocus sequence typing (MLST) measures nucleotide variations within several loci with slow accumulation of variation to enable the designation of allele numbers to determine a sequence type. The usage of whole genome sequence data enables the application of MLST, but also core and whole genome MLST for higher levels of strain discrimination with a negligible increase in experimental cost. An MLST database was developed alongside a seven loci scheme using publically available whole genome data from the sequence read archive. Sequence type designation and strain discrimination was compared to previously published data to ensure reproducibility. Multiple D. nodosus isolates from U.K. farms were directly compared to populations from other countries. The U.K. isolates define new clades within the global population of D. nodosus and predominantly consist of serogroups A, B and H, however serogroups C, D, E, and I were also found. Thescheme is publically available at https://pubmlst.org/dnodosus/