72 research outputs found
The utility of Pinus sylvestris L. in dendrochemical investigations: Pollution impact of lead mining and smelting in Darley Dale, Derbyshire, UK
This research investigates atmospheric pollution from an isolated and increasingly productive lead-smelting site by examining the dendrochemistry of Pinus sylvestris growing in the local environment and at control sites. Tree increment cores and soil in the rooting environment were analysed for lead content. Inter-site comparisons of lead-in-soil suggest that contamination of the soil may be a less important pathway for lead inclusion within wood than pathways via bark or needles. Levels of lead-in-wood (up to 38 mg kg−1) are at the upper end of those previously reported. There is evidence of radial translocation of lead towards the heartwood and variability in intra-site dendrochemical records. Mean site lead-in-wood records can however be related to a well-documented pollution chronology and also suggest the importance of local topography in the dispersal and deposition of particulate lead. This study demonstrates that P. sylvestris can be used to estimate the scale and timing of past pollution episodes in similar environmental contexts to those investigated at Darley Dale, where precisely dated pollution chronologies are lacking
Observation of electron transfer mediated decay in aqueous solution
Photoionization is at the heart of X ray photoelectron spectroscopy XPS , which gives access to important information on a sample s local chemical environment. Local and non local electronic decay after photoionization in which the refilling of core holes results in electron emission from either the initially ionized species or a neighbour, respectively have been well studied. However, electron transfer mediated decay ETMD , which involves the refilling of a core hole by an electron from a neighbouring species, has not yet been observed in condensed phase. Here we report the experimental observation of ETMD in an aqueous LiCl solution by detecting characteristic secondary low energy electrons using liquid microjet soft XPS. Experimental results are interpreted using molecular dynamics and high level ab initio calculations. We show that both solvent molecules and counterions participate in the ETMD processes, and different ion associations have distinctive spectral fingerprints. Furthermore, ETMD spectra are sensitive to coordination numbers, ion solvent distances and solvent arrangemen
Efficiency of Organelle Capture by Microtubules as a Function of Centrosome Nucleation Capacity: General Theory and the Special Case of Polyspermia
Transport of organelles along microtubules is essential for the cell metabolism and morphogenesis. The presented analysis derives the probability that an organelle of a given size comes in contact with the microtubule aster. The question is asked how this measure of functionality of the microtubule aster is controlled by the centrosome. A quantitative model is developed to address this question. It is shown that for the given set of cellular parameters, such as size and total tubulin content, a centrosome nucleation capacity exists that maximizes the probability of the organelle capture. The developed general model is then applied to the capture of the female pronucleus by microtubules assembled on the sperm centrosome, following physiologically polyspermic fertilization. This application highlights an unintuitive reflection of nonlinearity of the nucleated polymerization of the cellular pool of tubulin. The prediction that the sperm centrosome should lower its nucleation capacity in the face of the competition from the other sperm is a stark illustration of the new optimality principle. Overall, the model calls attention to the capabilities of the centrosomal pathway of regulation of the transport-related functionality of the microtubule cytoskeleton. It establishes a quantitative and conceptual framework that can guide experiment design and interpretation
Which patient will feel down, which will be happy? The need to study the genetic disposition of emotional states
Purpose In quality-of-life (QL) research, the genetic susceptibility of negative and positive emotions is frequently ignored, taken for granted, or treated as noise. The objectives are to describe: (1) the major findings of studies addressing the heritable and environmental causes of variation in negative and positive emotional states and (2) the major biological pathways of and genetic variants involved in these emotional states
Non-classical forms of pemphigus: pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus
The pemphigus group comprises the autoimmune intraepidermal blistering diseases classically divided into two major types: pemphigus vulgaris and pemphigus foliaceous. Pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus are rarer forms that present some clinical, histological and immunopathological characteristics that are different from the classical types. These are reviewed in this article. Future research may help definitively to locate the position of these forms in the pemphigus group, especially with regard to pemphigus herpetiformis and the IgG/ IgA pemphigus.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology DepartmentUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology and Pathology DepartmentsUNIFESP, EPM, Dermatology DepartmentUNIFESP, EPM, Dermatology and Pathology DepartmentsSciEL
Determinants of recovery from post-COVID-19 dyspnoea: analysis of UK prospective cohorts of hospitalised COVID-19 patients and community-based controls
Background The risk factors for recovery from COVID-19 dyspnoea are poorly understood. We investigated determinants of recovery from dyspnoea in adults with COVID-19 and compared these to determinants of recovery from non-COVID-19 dyspnoea. Methods We used data from two prospective cohort studies: PHOSP-COVID (patients hospitalised between March 2020 and April 2021 with COVID-19) and COVIDENCE UK (community cohort studied over the same time period). PHOSP-COVID data were collected during hospitalisation and at 5-month and 1-year follow-up visits. COVIDENCE UK data were obtained through baseline and monthly online questionnaires. Dyspnoea was measured in both cohorts with the Medical Research Council Dyspnoea Scale. We used multivariable logistic regression to identify determinants associated with a reduction in dyspnoea between 5-month and 1-year follow-up. Findings We included 990 PHOSP-COVID and 3309 COVIDENCE UK participants. We observed higher odds of improvement between 5-month and 1-year follow-up among PHOSP-COVID participants who were younger (odds ratio 1.02 per year, 95% CI 1.01–1.03), male (1.54, 1.16–2.04), neither obese nor severely obese (1.82, 1.06–3.13 and 4.19, 2.14–8.19, respectively), had no pre-existing anxiety or depression (1.56, 1.09–2.22) or cardiovascular disease (1.33, 1.00–1.79), and shorter hospital admission (1.01 per day, 1.00–1.02). Similar associations were found in those recovering from non-COVID-19 dyspnoea, excluding age (and length of hospital admission). Interpretation Factors associated with dyspnoea recovery at 1-year post-discharge among patients hospitalised with COVID-19 were similar to those among community controls without COVID-19. Funding PHOSP-COVID is supported by a grant from the MRC-UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research (NIHR) rapid response panel to tackle COVID-19. The views expressed in the publication are those of the author(s) and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health and Social Care. COVIDENCE UK is supported by the UK Research and Innovation, the National Institute for Health Research, and Barts Charity. The views expressed are those of the authors and not necessarily those of the funders
Breast cancer cells can switch between estrogen receptor α and ErbB signaling and combined treatment against both signaling pathways postpones development of resistance
Clinical characteristics with inflammation profiling of long COVID and association with 1-year recovery following hospitalisation in the UK: a prospective observational study
Background
No effective pharmacological or non-pharmacological interventions exist for patients with long COVID. We aimed to describe recovery 1 year after hospital discharge for COVID-19, identify factors associated with patient-perceived recovery, and identify potential therapeutic targets by describing the underlying inflammatory profiles of the previously described recovery clusters at 5 months after hospital discharge.
Methods
The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study recruiting adults (aged ≥18 years) discharged from hospital with COVID-19 across the UK. Recovery was assessed using patient-reported outcome measures, physical performance, and organ function at 5 months and 1 year after hospital discharge, and stratified by both patient-perceived recovery and recovery cluster. Hierarchical logistic regression modelling was performed for patient-perceived recovery at 1 year. Cluster analysis was done using the clustering large applications k-medoids approach using clinical outcomes at 5 months. Inflammatory protein profiling was analysed from plasma at the 5-month visit. This study is registered on the ISRCTN Registry, ISRCTN10980107, and recruitment is ongoing.
Findings
2320 participants discharged from hospital between March 7, 2020, and April 18, 2021, were assessed at 5 months after discharge and 807 (32·7%) participants completed both the 5-month and 1-year visits. 279 (35·6%) of these 807 patients were women and 505 (64·4%) were men, with a mean age of 58·7 (SD 12·5) years, and 224 (27·8%) had received invasive mechanical ventilation (WHO class 7–9). The proportion of patients reporting full recovery was unchanged between 5 months (501 [25·5%] of 1965) and 1 year (232 [28·9%] of 804). Factors associated with being less likely to report full recovery at 1 year were female sex (odds ratio 0·68 [95% CI 0·46–0·99]), obesity (0·50 [0·34–0·74]) and invasive mechanical ventilation (0·42 [0·23–0·76]). Cluster analysis (n=1636) corroborated the previously reported four clusters: very severe, severe, moderate with cognitive impairment, and mild, relating to the severity of physical health, mental health, and cognitive impairment at 5 months. We found increased inflammatory mediators of tissue damage and repair in both the very severe and the moderate with cognitive impairment clusters compared with the mild cluster, including IL-6 concentration, which was increased in both comparisons (n=626 participants). We found a substantial deficit in median EQ-5D-5L utility index from before COVID-19 (retrospective assessment; 0·88 [IQR 0·74–1·00]), at 5 months (0·74 [0·64–0·88]) to 1 year (0·75 [0·62–0·88]), with minimal improvements across all outcome measures at 1 year after discharge in the whole cohort and within each of the four clusters.
Interpretation
The sequelae of a hospital admission with COVID-19 were substantial 1 year after discharge across a range of health domains, with the minority in our cohort feeling fully recovered. Patient-perceived health-related quality of life was reduced at 1 year compared with before hospital admission. Systematic inflammation and obesity are potential treatable traits that warrant further investigation in clinical trials.
Funding
UK Research and Innovation and National Institute for Health Research
Preventing relapse of depression in primary care: a pilot study of the "Keeping the blues away" program
Objectives: To determine the effectiveness of “Keeping the blues away” (KBA), a manualised depression relapse prevention program for general practice, in reducing the relapse of depression compared with usual care (with the aim of halving the relapse rate), and in reducing depression severity and improving the process of care. Design and setting: A cluster randomised controlled trial conducted in 2004–2005 in South Australian general practices. Participants: 43 general practitioners from 23 urban and rural practices recruited 110 patients with depression (age range, 18–75 years). Intervention: GP training manual or patient manual and relaxation CD; 20 hours of training on depression, the study protocol, assessment tools and skills. Main outcome measures: Relative risk (RR) of depression relapse; depression severity and quality of life scores. Results: There were no significant differences in relapse rates between the groups (χ21 = 1.51; P = 0.23), although there was a non-significant tendency for relapse to be reduced in the KBA group (RR = 0.77; 95% CI, 0.50–2.05). Older patients (≥ 50 years) in the KBA group showed a significantly lower probability of relapse than those in the control group (P = 0.018). There was a decrease in depression scores in both groups. KBA participants had more severe depression at baseline, and the reduction in severity in those with symptoms for >6 months was nearly significant (P = 0.06). KBA was positively received by GPs and patients. Conclusions: Although this pilot study of a small sample did not achieve its primary outcome of reducing depression relapse by 50%, KBA was found to be a promising program for older patients and for those with more severe or persistent symptoms.Catherine A. Howell, Deborah A. Turnbull, Justin J. Beilby, Charlotte A. Marshall, Nancy Briggs and Wendy L. Newbur
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