The first comprehensive description of the biodiversity and biogeography of Antarctic and Sub-Antarctic intertidal communities

Aim To describe the distribution of biodiversity and biogeographical patterns of intertidal organisms in southern temperate and polar waters. We hypothesized that there would be differences in community structure between the Antarctic, which is most affected by ice, and the sub-Antarctic and other neighbouring regions. We also hypothesized that rafting and West Wind Drift will be the significant drivers of biogeographical patterns. Additionally, the size, age, isolation, volcanic or glacial history of a region and the presence of large, beach dwelling, mammals and birds would all play a role in determining the level of biodiversity observed. Location South Atlantic, Indian and Pacific Oceans and the Southern Ocean. Methods We examined all available intertidal records from the Antarctic and sub-Antarctic with additional data from neighbouring regions for comparison and context. We compiled 3902 occurrences of 1416 species of high southern latitude intertidal organisms from 229 locations and used PRIMER 6 to perform multivariate statistical analyses. Results The Antarctic and sub-Antarctic are shown to be distinct biogeographical regions, with patterns driven by a small number of widely distributed species. These wide-ranging molluscs and macroalgae dominate the biogeographical structure of the Southern Ocean intertidal, most likely as a result of rafting in the Antarctic Circumpolar Current. East Antarctic intertidal habitats are potentially isolated by the Ross and Weddell Sea ice shelves but represent a great unknown in this biogeographical scheme. Main Conclusions The view that the Antarctic intertidal is a lifeless desert does not hold true, with Antarctic Peninsula intertidal communities being richer and more diverse than those in southern South America and the sub-Antarctic islands. Changing conditions in the Antarctic and sub-Antarctic intertidal mean that a representative baseline is needed (acquired through standardized and quantitative sampling) to assess future changes and to detect any invasive species

Zoogeographic and Richness Patterns in Southern Ocean Benthos

This thesis describes the large scale biogeographic patterns found in the Southern Ocean benthos. Using SOMBASE and SCAR-MarBIN, the two most comprehensive, georeferenced databases of Antarctic marine biodiversity ever compiled, a range of taxa were investigated but focusing on the Mollusca, Bryozoa and Pycnogonida. Over 8,000 species of marine invertebrates from over 5,000 sites constituting -34,000 records were used in the analyses. The strong faunal links between the Antarctic and South America were confirmed but I found little evidence for a biogeographical relationship between the Antarctic or South America and New Zealand or Tasmania. Regional levels of Southern Ocean endemism proved the influence of the Antarctic Circumpolar Current upon the distribution of Southern Ocean benthos. My study shows the Southern Ocean as a ‘single functional unit’ with no evidence for an earlier proposed biogeographical split between East and West Antarctica. Some general rules on Antarctic benthic biogeography are viable, including species endemism rates of around 50% and a definite distinction between the sub-Antarctic islands influenced by either South America or by New Zealand. In the context of potential shifts in species distribution with climate change I investigated the current ranges of selected Southern Ocean taxa (Mollusca, Amphipoda, Ophiuroidea and Hexacorala), and looked for hotspots of coinciding northern and southern geographic range limits. Southern Patagonia, South Georgia and Kerguelen had the greatest range-limit hotspots. Monitoring range shifts in these key places and taxa will enable us to track the influence and effects of climate change on benthic species distributions in the Southern Ocean

Breaking all the rules: The first recorded hard substrate sessile benthic community far beneath an Antarctic ice shelf

The seafloor beneath floating ice shelves accounts roughly a third of the Antarctic’s 5 million km2 of continental shelf. Prior to this study, our knowledge of these habitats and the life they support was restricted to what has been observed from eight boreholes drilled for geological and glaciological studies. The established theory of sub-ice shelf biogeography is that both functional and taxonomic diversities decrease along a nutrient gradient with distance from the ice shelf front, resulting in a depauperate fauna, dominated by mobile scavengers and predators toward the grounding line. Mobile macro-benthic life and mega-benthic life have been observed as far as 700 km under an ice shelf. New observations from two boreholes in the Filchner-Ronne Ice Shelf challenge the idea that sessile organisms reduce in prevalence the further under the ice you go. The discovery of an established community consisting of only sessile, probably filter feeding, organisms (sponges and other taxa) on a boulder 260 km from the ice front raises significant questions, especially when the local currents suggest that this community is somewhere between 625 km and 1500 km in the direction of water flow from the nearest region of photosynthesis. This new evidence requires us to rethink our ideas with regard to the diversity of community types found under ice shelves, the key factors which control their distribution and their vulnerability to environmental change and ice shelf collapse

Physical Activity in a Cohort of Medicaid Beneficiaries with Physical Impairments: Recruitment and Outcomes

This document reports on research conducted by the University of Montana for the Office of Disability and Health at the Centers for Disease Control and Prevention. The research project, conducted between September 30, 2000 and September 29, 2004 was accomplished in three separate but related studies. The research was conducted at the New Directions programs, a community-based health promotion and wellness clinic operated through the rural Institute on Disabilities at the University of Montana. We collaborated with the State Department of Medicaid to recruit Medicaid beneficiaries with mobility impairments in Missoula County to participate in the research. We recruited 368 of a possible 1535 people who were listed in administrative records as having a disability. We used surveys collected from this cohort to further assess eligibility criteria and selected 224 individuals to participate in the research projects. Additionally, we included individuals who were not Medicaid beneficiaries in studies two and three, but were using our fitness facility and consented to complete measures for the study

Pan-Atlantic Comparison of Deep-Sea Macro- and Megabenthos

Deep-sea benthic fauna is vital for a well-functioning marine ecosystem but is increasingly under threat from a changing environment. To monitor and conserve this fauna, an understanding of their large-scale spatial and bathymetric distribution and their environmental drivers is necessary. In this study, we conduct a multivariate analysis on abundance benthic fauna data collected at the phylum and multitaxon levels using an epibenthic sledge (EBS) across the Atlantic, and identify the environmental factors that affect such data. Our findings show a decrease in abundance with depth in most of the Atlantic but find relatively heterogeneous abundances with depth within the Southern Ocean. Principal component analyses indicate differences in environmental conditions south of the Antarctic Polar Front (~52° S), outlining contrasts in the quantities of macronutrients and physical factors. Despite this, community composition seemed markedly similar throughout the Atlantic with the Antarctic Circumpolar Current seemingly not affecting benthic community composition for higher taxonomic levels. Those differences that did occur were largely caused by benthic chlorophyll, benthic iron, and surface silicate through a Bio-ENV. Overall, we argue that further large-scale spatial and bathymetric distribution studies are important amid environmental changes that are driving shifts in benthic community abundance and composition

Periscope Proteins are variable length regulators of bacterial cell surface interactions

Changes at the cell surface enable bacteria to survive in dynamic environments, such as diverse niches of the human host. Here, we reveal “Periscope Proteins” as a widespread mechanism of bacterial surface alteration mediated through protein length variation. Tandem arrays of highly similar folded domains can form an elongated rod-like structure; thus, variation in the number of domains determines how far an N-terminal host ligand binding domain projects from the cell surface. Supported by newly available long-read genome sequencing data, we propose that this class could contain over 50 distinct proteins, including those implicated in host colonization and biofilm formation by human pathogens. In large multidomain proteins, sequence divergence between adjacent domains appears to reduce interdomain misfolding. Periscope Proteins break this “rule,” suggesting that their length variability plays an important role in regulating bacterial interactions with host surfaces, other bacteria, and the immune system

Frontotemporal dementia and its subtypes: a genome-wide association study

SummaryBackground Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes—MAPT, GRN, and C9orf72—have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder. Methods We did a two-stage genome-wide association study on clinical FTD, analysing samples from 3526 patients with {FTD} and 9402 healthy controls. To reduce genetic heterogeneity, all participants were of European ancestry. In the discovery phase (samples from 2154 patients with {FTD} and 4308 controls), we did separate association analyses for each {FTD} subtype (behavioural variant FTD, semantic dementia, progressive non-fluent aphasia, and {FTD} overlapping with motor neuron disease FTD-MND), followed by a meta-analysis of the entire dataset. We carried forward replication of the novel suggestive loci in an independent sample series (samples from 1372 patients and 5094 controls) and then did joint phase and brain expression and methylation quantitative trait loci analyses for the associated (p<5 × 10−8) single-nucleotide polymorphisms. Findings We identified novel associations exceeding the genome-wide significance threshold (p<5 × 10−8). Combined (joint) analyses of discovery and replication phases showed genome-wide significant association at 6p21.3, \{HLA\} locus (immune system), for rs9268877 (p=1·05 × 10−8; odds ratio=1·204 95% \{CI\} 1·11–1·30), rs9268856 (p=5·51 × 10−9; 0·809 0·76–0·86) and rs1980493 (p value=1·57 × 10−8, 0·775 0·69–0·86) in the entire cohort. We also identified a potential novel locus at 11q14, encompassing RAB38/CTSC (the transcripts of which are related to lysosomal biology), for the behavioural \{FTD\} subtype for which joint analyses showed suggestive association for rs302668 (p=2·44 × 10−7; 0·814 0·71–0·92). Analysis of expression and methylation quantitative trait loci data suggested that these loci might affect expression and methylation in cis. Interpretation Our findings suggest that immune system processes (link to 6p21.3) and possibly lysosomal and autophagy pathways (link to 11q14) are potentially involved in FTD. Our findings need to be replicated to better define the association of the newly identified loci with disease and to shed light on the pathomechanisms contributing to FTD. Funding The National Institute of Neurological Disorders and Stroke and National Institute on Aging, the Wellcome/MRC Centre on Parkinson's disease, Alzheimer's Research UK, and Texas Tech University Health Sciences Center

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Implementation of corticosteroids in treating COVID-19 in the ISARIC WHO Clinical Characterisation Protocol UK:prospective observational cohort study

BACKGROUND: Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care. METHODS: We did an audit of clinical implementation of corticosteroids in a prospective, observational, cohort study in 237 UK acute care hospitals between March 16, 2020, and April 14, 2021, restricted to patients aged 18 years or older with proven or high likelihood of COVID-19, who received supplementary oxygen. The primary outcome was administration of dexamethasone, prednisolone, hydrocortisone, or methylprednisolone. This study is registered with ISRCTN, ISRCTN66726260. FINDINGS: Between June 17, 2020, and April 14, 2021, 47 795 (75·2%) of 63 525 of patients on supplementary oxygen received corticosteroids, higher among patients requiring critical care than in those who received ward care (11 185 [86·6%] of 12 909 vs 36 415 [72·4%] of 50 278). Patients 50 years or older were significantly less likely to receive corticosteroids than those younger than 50 years (adjusted odds ratio 0·79 [95% CI 0·70–0·89], p=0·0001, for 70–79 years; 0·52 [0·46–0·58], p80 years), independent of patient demographics and illness severity. 84 (54·2%) of 155 pregnant women received corticosteroids. Rates of corticosteroid administration increased from 27·5% in the week before June 16, 2020, to 75–80% in January, 2021. INTERPRETATION: Implementation of corticosteroids into clinical practice in the UK for patients with COVID-19 has been successful, but not universal. Patients older than 70 years, independent of illness severity, chronic neurological disease, and dementia, were less likely to receive corticosteroids than those who were younger, as were pregnant women. This could reflect appropriate clinical decision making, but the possibility of inequitable access to life-saving care should be considered. FUNDING: UK National Institute for Health Research and UK Medical Research Council