Socio-ecology of the Marsh Rice Rat (\u3ci\u3eOryzomys palustris\u3c/i\u3e) and the Spatio-Temporal Distribution of Bayou Virus in Coastal Texas

Along the southeastern coast of the United States of America (USA), the marsh rice rat (Oryzomys palustris) is the primary host for the hantavirus genotype Bayou. According to the socio-ecological model for a territorial, polygamous species, females should be distributed across space and time by habitat resources and predation risks, whereas males should space themselves according to the degree of female aggregation and reproductive synchrony. To investigate how females affect the male-male transmission paradigm of Bayou virus, rodents were captured, marked, released, and re-captured in two macrohabitat types across a 30-month period. Microhabitat cover variables were quantified around the individual trap stations. A geodatabase was created from habitat and rodent capture data and analysed in a geographical information system. The ratio of breeding to non-breeding females was ~1:1, with breeding females overly dispersed and non-breeding females randomly dispersed. Spatial analyses revealed both macro- and microhabitat preferences in females. Compared to sero-negatives, higher proportions of seropositive adult males were found consistently within closer proximities to breeding females but not to non-breeding females, indicating that male locations were not driven simply by habitat selection. Activities to acquire dispersed receptive females could be an important driver of Bayou virus transmission among male hosts. To date, socio-ecological theory has received little attention as an investigative framework for studying pathogen dynamics in small, solitary mammals. Herein, we describe an interdisciplinary effort providing a novel approach to elucidate the complexity of hantavirus trafficking and maintenance in rodent populations of a coastal marsh ecosystem

Women’s experiences of wearing therapeutic footwear in three European countries

Background: Therapeutic footwear is recommended for those people with severe foot problems associated with rheumatoid arthritis (RA). However, it is known that many do not wear them. Although previous European studies have recommended service and footwear design improvements, it is not known if services have improved or if this footwear meets the personal needs of people with RA. As an earlier study found that this footwear has more impact on women than males, this study explores women’s experiences of the process of being provided with it and wearing it. No previous work has compared women’s experiences of this footwear in different countries, therefore this study aimed to explore the potential differences between the UK, the Netherlands and Spain. Method: Women with RA and experience of wearing therapeutic footwear were purposively recruited. Ten women with RA were interviewed in each of the three countries. An interpretive phenomenological approach (IPA) was adopted during data collection and analysis. Conversational style interviews were used to collect the data. Results: Six themes were identified: feet being visibly different because of RA; the referring practitioners’ approach to the patient; the dispensing practitioners’ approach to the patient; the footwear being visible as different to others; footwear influencing social participation; and the women’s wishes for improved footwear services. Despite their nationality, these women revealed that therapeutic footwear invokes emotions of sadness, shame and anger and that it is often the final and symbolic marker of the effects of RA on self perception and their changed lives. This results in severe restriction of important activities, particularly those involving social participation. However, where a patient focussed approach was used, particularly by the practitioners in Spain and the Netherlands, the acceptance of this footwear was much more evident and there was less wastage as a result of the footwear being prescribed and then not worn. In the UK, the women were more likely to passively accept the footwear with the only choice being to reject it once it had been provided. All the women were vocal about what would improve their experiences and this centred on the consultation with both the referring practitioner and the practitioner that provides the footwear. Conclusion: This unique study, carried out in three countries has revealed emotive and personal accounts of what it is like to have an item of clothing replaced with an ‘intervention’. The participant’s experience of their consultations with practitioners has revealed the tension between the practitioners’ requirements and the women’s ‘social’ needs. Practitioners need greater understanding of the social and emotional consequences of using therapeutic footwear as an intervention

Foot orthoses for the management of low back pain: a qualitative approach capturing the patient’s perspective

Background: The onset of non specific low back pain is associated with heavy lifting, age, female gender, and poor general health, with psychological factors being predictors of it becoming chronic. Additionally, it is thought that altered lower limb biomechanics are a contributory factor, with foot orthoses increasingly being considered as an appropriate intervention by physiotherapists and podiatrists. However, research into the effect of foot orthoses is inconclusive, primarily focusing on the biomechanical effect and not the symptomatic relief from the patient’s perspective. The aim of this study was to explore the breadth of patients’ experiences of being provided with foot orthoses and to evaluate any changes in their back pain following this experience. Method: Following ethical approval, participants (n = 25) with non-specific low back pain associated with altered lower limb biomechanics were provided with customised foot orthoses. At 16 weeks after being provided with the foot orthoses, conversational style interviews were carried out with each patient. An interpretivistic phenomenological approach was adopted for the data collection and analysis. Results: For these participants, foot orthoses appeared to be effective. However, the main influence on this outcome was the consultation process and a patient focussed approach. The consultation was an opportunity for fostering mutual understanding, with verbal and visual explanation reassuring the patient and this influenced the patient’s beliefs, their engagement with the foot orthoses (physical) and their experience of low back pain (psychological). Conclusion: Clinicians need to adopt ‘psychologically informed practice’ in relation to the provision of foot orthoses. Likewise, researchers should consider all the influencing factors found in this study, both in relation to their study protocol and the outcomes they plan to measure. Keywords: Low back pain, Foot orthoses, Qualitative research, Informatio

Paramedic Acute Stroke Treatment Assessment (PASTA): study protocol for a randomised controlled trial

BACKGROUND: Despite evidence from clinical trials that intravenous (IV) thrombolysis is a cost-effective treatment for selected acute ischaemic stroke patients, there remain large variations in the rate of IV thrombolysis delivery between stroke services. This study is evaluating whether an enhanced care pathway delivered by paramedics (the Paramedic Acute Stroke Treatment Assessment (PASTA)) could increase the number of patients who receive IV thrombolysis treatment. METHODS: Study design: Cluster randomised trial with economic analysis and parallel process evaluation. SETTING: National Health Service ambulance services, emergency departments and hyper-acute stroke units within three geographical regions of England and Wales. Randomisation: Ambulance stations within each region are the units of randomisation. According to station allocation, paramedics based at a station deliver the PASTA pathway (intervention) or continue with standard stroke care (control). Study intervention: The PASTA pathway includes structured pre-hospital information collection, prompted pre-notification, structured handover of information in hospital and assistance with simple tasks during the initial hospital assessment. Study-trained intervention group paramedics deliver this pathway to adults within 4 h of suspected stroke onset. Study control: Standard stroke care according to national and local guidelines for the pre-hospital and hospital assessment of suspected stroke. PARTICIPANTS: Participants enrolled in the study are adults with confirmed stroke who were assessed by a study paramedic within 4 h of symptom onset. PRIMARY OUTCOME: Proportion of participants receiving IV thrombolysis. SAMPLE SIZE: 1297 participants provide 90% power to detect a 10% difference in the proportion of patients receiving IV thrombolysis. DISCUSSION: The results from this trial will determine whether an enhanced care pathway delivered by paramedics can increase thrombolysis delivery rates. TRIAL REGISTRATION: ISRCTN registry, ISRCTN12418919 . Registered on 5 November 2015

Single-cell multi-omics analysis of the immune response in COVID-19

Funder: Lister Institute of Preventive Medicine; doi: https://doi.org/10.13039/501100001255Funder: University College London, Birkbeck MRC Doctoral Training ProgrammeFunder: The Jikei University School of MedicineFunder: Action Medical Research (GN2779)Funder: NIHR Clinical Lectureship (CL-2017-01-004)Funder: NIHR (ACF-2018-01-004) and the BMA FoundationFunder: Chan Zuckerberg Initiative (grant 2017-174169) and from Wellcome (WT211276/Z/18/Z and Sanger core grant WT206194)Funder: UKRI Innovation/Rutherford Fund Fellowship allocated by the MRC and the UK Regenerative Medicine Platform (MR/5005579/1 to M.Z.N.). M.Z.N. and K.B.M. have been funded by the Rosetrees Trust (M944)Funder: Barbour FoundationFunder: ERC Consolidator and EU MRG-Grammar awardsFunder: Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002)Funder: European Molecular Biology Laboratory (EMBL)Abstract: Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy

Socio-ecology of the marsh rice rat (Oryzomys palustris) and the spatio-temporal distribution of Bayou virus in coastal Texas

Along the southeastern coast of the United States of America (USA), the marsh rice rat (Oryzomys palustris) is the primary host for the hantavirus, genotype Bayou. According to the socio-ecological model for a territorial, polygamous species, females should be distributed across space and time by habitat resources and predation risks, whereas males should space themselves according to the degree of female aggregation and reproductive synchrony. To investigate how females affect the male-male transmission paradigm of Bayou virus, rodents were captured, marked, released in two macrohabitat types and followed across a 30-month period. Microhabitat cover variables were quantified around the individual trap stations. A geodatabase was created from habitat and rodent capture data and analysed in a geographical information system. The ratio of breeding to non-breeding females was ~1:1, with breeding females overly dispersed and non-breeding females randomly dispersed. Spatial analyses revealed both macro- and microhabitat preferences in females. Compared to seronegatives, higher proportions of seropositive adult males were found consistently within closer proximities to breeding females but not to non-breeding females, indicating that male locations were not driven simply by habitat selection. Activities to acquire dispersed receptive females could be an important driver of Bayou virus transmission among male hosts. Herein, we describe an interdisciplinary effort providing a novel approach to elucidate the complexity of hantavirus trafficking and maintenance in rodent populations of a coastal marsh ecosystem

Improvement in symptoms and signs in the forefoot of patients with rheumatoid arthritis treated with anti-TNF therapy

Background: Inhibition of tumour necrosis factor (TNF) is an effective way of reducing synovitis and preventing joint damage in rheumatoid arthritis (RA), yet very little is known about its specific effect on foot pain and disability. The aim of this study was to evaluate whether anti-TNF therapy alters the presence of forefoot pathology and/or reduces foot pain and disability. Methods: Consecutive RA patients starting anti-TNF therapy (infliximab, etanercept, adalimumab) were assessed for presence of synovial hypertrophy and synovitis in the 2nd and 5th metatarso-phalangeal (MTP) joints and plantar forefoot bursal hypertrophy before and 12 weeks after therapy. Tender MTP joints and swollen bursae were established clinically by an experienced podiatrist and ultrasound (US) images were acquired and interpreted by a radiologist. Assessment of patient reported disease impact on the foot was performed using the Manchester Foot Pain and Disability Index (MFPDI). RResults: 31 patients (24 female, 7 male) with RA (12 seronegative, 19 seropositive) completed the study: mean age 59.6 (SD 10.1) years, disease duration 11.1 (SD 10.5) years, and previous number of Disease Modifying Anti Rheumatic Drugs 3.0 (1.6). Significant differences after therapy were found for Erythrocyte Sedimentation Rate (t=4.014, p&lt;0.001), C-reactive protein (t=3.889, p=0.001), 28 joint Disease Activity Score (t=3.712, p=.0.001), Visual Analog Scale (t=2.735, p=0.011) and Manchester Foot Pain and Disability Index (t=3.712, p=0.001). Presence of MTP joint synovial hypertrophy on US was noted in 67.5% of joints at baseline and 54.8% of joints at twelve weeks. Presence of plantar forefoot bursal hypertrophy on US was noted in 83.3% of feet at baseline and 75% at twelve weeks. Although there was a trend for reduction in observed presence of person specific forefoot pathology, when the frequencies were analysed (McNemar) this was not significant. Conclusions: Significant improvements were seen in patient reported foot pain and disability 12 weeks after commencing TNF inhibition in RA, but this may not be enough time to detect changes in forefoot pathology.<br/

The diagnosis of urinary tract infections in young children (DUTY): protocol for a diagnostic and prospective observational study to derive and validate a clinical algorithm for the diagnosis of UTI in children presenting to primary care with an acute illness

Background: urinary tract infection (UTI) is common in children, and may cause serious illness and recurrent symptoms. However, obtaining a urine sample from young children in primary care is challenging and not feasible for large numbers. Evidence regarding the predictive value of symptoms, signs and urinalysis for UTI in young children is urgently needed to help primary care clinicians better identify children who should be investigated for UTI. This paper describes the protocol for the Diagnosis of Urinary Tract infection in Young children (DUTY) study. The overall study aim is to derive and validate a cost-effective clinical algorithm for the diagnosis of UTI in children presenting to primary care acutely unwell.Methods/design: DUTY is a multicentre, diagnostic and prospective observational study aiming to recruit at least 7,000 children aged before their fifth birthday, being assessed in primary care for any acute, non-traumatic, illness of???28 days duration. Urine samples will be obtained from eligible consented children, and data collected on medical history and presenting symptoms and signs. Urine samples will be dipstick tested in general practice and sent for microbiological analysis. All children with culture positive urines and a random sample of children with urine culture results in other, non-positive categories will be followed up to record symptom duration and healthcare resource use. A diagnostic algorithm will be constructed and validated and an economic evaluation conducted.The primary outcome will be a validated diagnostic algorithm using a reference standard of a pure/predominant growth of at least &gt;103, but usually &gt;105 CFU/mL of one, but no more than two uropathogens.We will use logistic regression to identify the clinical predictors (i.e. demographic, medical history, presenting signs and symptoms and urine dipstick analysis results) most strongly associated with a positive urine culture result. We will then use economic evaluation to compare the cost effectiveness of the candidate prediction rules.Discussion: this study will provide novel, clinically important information on the diagnostic features of childhood UTI and the cost effectiveness of a validated prediction rule, to help primary care clinicians improve the efficiency of their diagnostic strategy for UTI in young childre