Distribution of metals and radionuclides in the lichens Cladonia rangiferina and C. mitis from the past uranium mining region of Elliot Lake, Ontario, Canada.

The present study was performed in the Elliot Lake area (Ontario, Canada), a site of uranium mining and milling for nearly 40 years between 1950's and 1990's. Although mining activities ceased in the mid-1990's, the site hosts several tailings management areas (TMAs) which are under ongoing rehabilitation and monitoring. Several surveys using lichens as a biomonitoring tool were completed in the 1980s and the 1990s to assess the levels of contaminants. The present survey aimed to re-visit the historical surveys, and to determine the current status of environmental recovery of the area. Our survey consisted of sampling two lichen species, Cladonia rangiferina and C. mitis, in an area covering up to 50 km from the former mining operation and the TMAs. The results reported in this work indicated that the levels of metals and radionuclides, diagnostic of mining operations, have decreased over time: particularly, the U, Th and Pb levels in both lichen species dropped by about two orders of magnitude by the 2020's compared to the 1980's. Likewise, the Cs-137 levels in both lichen species reflect present day global background. The study provides a new set of present-day regional baseline elemental concentrations for other metals that are associated with mining (Cd, As, Ti, Cs). Finally, there were weak but statistically significant differences in the levels of some elements (U, Th, Cd) between the two lichens, suggesting these two species might have different capture mechanisms or retention abilities.

A review on the use of lichens as a biomonitoring tool for environmental radioactivity.

Lichens have been widely used as a biomonitoring tool to record the distribution and concentration of airborne radioactivity and pollutants such as metals. There are limitations, however: although pollutants can be preserved in lichen tissues for long periods of time, not all radioactive and inert elements behave similarly. The chemical species of elements at the source, once captured, and the mode of storage within lichens play a role in this biomonitoring tool. Lichens are a symbiotic association of an algal or cyanobacterial partner (photobiont) with a fungal host (mycobiont). Lichens grow independently of the host substrates, including rocks, soils, trees and human-made structures. Lacking a root system, lichen nutrient or contaminant uptake is mostly through direct atmospheric inputs, mainly as wet and dry deposition. As lichens grow in a large variety of environments and are resilient in harsh climates, they are adapted to capture and retain nutrients from airborne sources. The context of this review partially relates to future deployment of small modular reactors (SMRs) and mining in remote areas of Canada. SMRs have been identified as a future source of energy (electricity and heat) for remote off-grid mines, potentially replacing diesel fuel generation facilities. For licensing purposes, SMR deployment and mine development requires capabilities to monitor background contaminants (natural radioactivity and metals) before, during and after deployment, including for decommissioning and removal. Key aspects reviewed herein include: (1) how lichens have been used in the past to monitor radioactivity; (2) radiocontaminants capture and storage in lichens; (3) longevity of radiocontaminant storage in lichen tissues; and (4) limitations of lichens use for monitoring radiocontaminants and selected metals.

Microbial biomass and activity dynamics in restored lands in a metal contaminated region.

Soil microbial communities are important for biogeochemical processes, along with the cycling of nutrients in an ecosystem. Their enzymatic activities are key indicators of their responses to stress. The objective of this research was to assess the effect of land reclamation on microbial biomass and activities in soils impacted by metal contamination. Phospholipid fatty acid analysis (PLFA) (PLFA) results revealed a significant increase in total microbial biomass, fungi, actinomycetes, and bacteria when limed soils were compared to unlimed samples. This change in microbial biomass was associated with a significant increase of pH. The overall level of the ß-glucosidase (BG), cellobiohydrolase (CBH), and aryl sulfatase (AS) activities was significantly higher in the dolomitic limestone treated soils than in the untreated samples. However, the activity of glycine aminopeptidase (GAP) was significantly lower in the limed soil than in unlimed samples used as reference. No significant differences (P ≥ 0.05) were observed between the two types of lands (limed vs unlimed) for other enzymes tested, which includes ß-N-acetylglucosaminidase (NAGase), acid phosphatase (AP), alkaline phosphatase (ALP), leucine aminopeptidase (LAP), and peroxidase (PER). The levels of enzymatic responses also varied among sites. Overall, this study revealed for the first time the effects of liming on soil microbial activities in recently reclaimed sites damaged by metals.

Changes in ambient air quality and atmospheric composition and reactivity in the South East of the UK as a result of the COVID-19 lockdown.

The COVID-19 pandemic forced governments around the world to impose restrictions on daily life to prevent the spread of the virus. This resulted in unprecedented reductions in anthropogenic activity, and reduced emissions of certain air pollutants, namely oxides of nitrogen. The UK 'lockdown' was enforced on 23/03/2020, which led to restrictions on movement, social interaction, and 'non-essential' businesses and services. This study employed an ensemble of measurement and modelling techniques to investigate changes in air quality, atmospheric composition and boundary layer reactivity in the South East of the UK post-lockdown. The techniques employed included in-situ gas- and particle-phase monitoring within central and local authority air quality monitoring networks, remote sensing by long path Differential Optical Absorption Spectroscopy and Sentinel-5P's TROPOMI, and detailed 0-D chemical box modelling. Findings showed that de-trended NO2 concentrations decreased by an average of 14-38% when compared to the mean of the same period over the preceding 5-years. We found that de-trended particulate matter concentrations had been influenced by interregional pollution episodes, and de-trended ozone concentrations had increased across most sites, by up to 15%, such that total Ox levels were roughly preserved. 0-D chemical box model simulations showed the observed increases in ozone concentrations during lockdown under the hydrocarbon-limited ozone production regime, where total NOx decreased proportionally greater than total non-methane hydrocarbons, which led to an increase in total hydroxyl, peroxy and organic peroxy radicals. These findings suggest a more complex scenario in terms of changes in air quality owing to the COVID-19 lockdown than originally reported and provide a window into the future to illustrate potential outcomes of policy interventions seeking large-scale NOx emissions reductions without due consideration of other reactive trace species.

Stage III Non-small Cell Lung Cancer Management in England.

AIMS: We present the first analysis of the management and outcomes of stage III non-small cell lung cancer (NSCLC) conducted in England using National Lung Cancer Audit data. MATERIALS AND METHODS: Patients diagnosed with stage III NSCLC in 2016 were identified. Linked datasets (including Hospital Episode Statistics, the National Radiotherapy Dataset, the Systemic Anti-Cancer Dataset, pathology reports and death certificate data) were used to categorise the treatment received. Kaplan-Meier survival curves were obtained, with survival defined from the date of diagnosis to the date of death. RESULTS: In total, 6276 cases of stage III NSCLC were analysed: 3827 stage IIIA and 2449 stage IIIB; 1047 (17%) patients were treated with radical radiotherapy with 676 (11%) of these also receiving chemotherapy. Twenty per cent of patients with stage IIIA disease underwent surgery, with half of these also receiving chemotherapy, predominantly delivered in the adjuvant setting. Of note, 2148 (34%) patients received palliative-intent treatment and 2265 (36%) received no active anti-cancer treatment. The 1-year survival was 32.9% (37.4% for stage IIIA), with the highest survival seen for those patients receiving chemotherapy and surgery. CONCLUSIONS: We highlight important gaps in the optimal care of patients with stage III NSCLC in England. Multimodality treatment with either surgery or radical radiotherapy combined with chemotherapy was delivered to less than one-fifth of patients, even though these regimens are considered optimal. Timely access to specialist resources and staff, the practice of effective shared decision making and challenging preconceptions have the potential to optimise management.

Variation in lung cancer resources and workload: results from the first national lung cancer organisational audit.

We report the findings of the first national lung cancer organisational audit. The results demonstrate marked variation in service provision and workload of some lung cancer specialists. For example, over half of the clinical nurse specialists report case volumes over recommended numbers. Some trusts have no access to key treatments such as video assisted thoracoscopy (VAT) lobectomy and stereotactic radiotherapy. Multivariate regression analysis demonstrated an association between higher surgical resection rates and the on-site availability of advanced staging and therapeutic modalities, for example, PET scan and VAT lobectomy. We conclude by making a number of recommendations to address the variation in lung cancer care.

Demographics, management and survival of patients with malignant pleural mesothelioma in the National Lung Cancer Audit in England and Wales.

INTRODUCTION AND METHODS: Malignant pleural mesothelioma (MPM) is an uncommon cancer with poor survival. We have used data collected for the UK National Lung Cancer Audit to assess current practice and to highlight regional variation in the management of mesothelioma patients, as well as to describe survival patterns in subgroups. RESULTS: Our data on 8740 cases seen in hospitals in England and Wales is the largest cohort of MPM in the literature and represents approximately 80% of the total incident cases. 83% are male and median age is 73 years. Performance status is recorded in 81% and of these approximately 70% are PS 0-2. Stage is poorly recorded and unreliable in this dataset. The patient pathway is similar to lung cancer with approximately one-fifth having a non-elective referral to secondary care. A histo-cytological diagnosis is made in 87% and varies across organisations. Only 67% have anti-cancer treatment, and this also varies across organisations, but there has been an annual increase in the proportion receiving chemotherapy. Overall median survival was 9.5 months, with a 1YS of 41.4% and 3YS of 12.0%, but was strongly linked to performance status and histological subtype. Median survival also varied by cancer network from 209 days to 349 days, but appeared to increase from of 9.2 months in 2008 to 10.5 months in 2012. CONCLUSION: Our data provide a large scale, detailed assessment of MPM epidemiology, treatment choices and outcomes. Incidence is increasing in line with predictions and uptake of treatments has generally mirrored publication of key MPM treatment trials, in particular increasing use of chemotherapy but low uptake of radical surgery. However, there is significant variation in care patterns and outcomes that may reflect limited expertise in area with low incidence. Initiatives to improve outcomes should include improved recording of clinical stage.

Risk factors and survival outcome for non-elective referral in non-small cell lung cancer patients--analysis based on the National Lung Cancer Audit.

INTRODUCTION: Survival after diagnosis of lung cancer is poor and seemingly lower in the UK than other Western countries, due in large part to late presentation with advanced disease precluding curative treatment. Recent research suggests that around one-third of lung cancer patients reach specialist care after emergency presentation and have a worse survival outcome. Confirmation of these data and understanding which patients are affected may allow a targeted approach to improving outcomes. METHODS: We used data from the UK National Lung Cancer Audit in a multivariate logistic regression model to quantify the association of non-elective referral in non-small cell lung cancer patients with covariates including age, sex, stage, performance status, co-morbidity and socioeconomic status and used the Kaplan-Meier method and Cox proportional hazards model to quantify survival by source of referral. RESULTS: In an analysis of 133,530 cases of NSCLC who presented 2006-2011, 19% of patients were referred non-electively (following an emergency admission to hospital or following an emergency presentation to A&E). This route of referral was strongly associated with more advanced disease stage (e.g. in Stage IV - OR: 2.34, 95% CI: 2.14-2.57, p<0.001) and worse performance status (e.g. in PS 4 - OR: 7.28, 95% CI: 6.75-7.86, p<0.001), but was also independently associated with worse socioeconomic status, and extremes of age. These patients were more likely to have died within 1 year of diagnosis (hazard ratio of 1.51 (95% CI: 1.49-1.54) after adjustment for key clinical variables. CONCLUSION: Our data confirm and quantify poorer survival in lung cancer patients who are referred non-electively to specialist care, which is more common in patients with poorer performance status, higher disease stage and less advantaged socioeconomic status. Work to tackle this late presentation should be urgently accelerated, since its realisation holds the promise of improved outcomes and better healthcare resource utilisation.

Exploring variations in lung cancer care across the UK--the 'story so far' for the National Lung Cancer Audit.

The National Lung Cancer Audit was developed to improve the quality and outcomes of services for patients with lung cancer, knowing that outcomes vary widely across the UK and are poor compared to other western countries. After five years the audit is capturing approximately 100% of the expected number of incident cases across hospitals in England, Wales, Scotland, Northern Ireland and Jersey. Measures of process and outcome have improved over the audit period, such as the histological confirmation rate (64-76%), the proportion of patients discussed in a multidisciplinary team meeting (78-94%), and the proportion of patients having anti-cancer treatment (43-59%), surgical resection (9-14%) and small cell lung cancer chemotherapy (58-66%). These national averages hide wide variations between hospitals providing lung cancer care which cannot be accounted for by differences in casemix. This paper describes the evolution of the audit, and describes the ways in which it may have improved clinical practice.

Comparative soil metal analyses in Sudbury (Ontario, Canada) and Lubumbashi (Katanga, DR-Congo).

DR-Congo is a main world producer of copper (Cu) and cobalt (Co). Several hydrometallurgical plants and smelters also produced zinc, arsenic, and cadmium as by-products. In Sudbury (Canada), the production of nickel, copper and other metals has been maintained at high levels while industrial SO(2) emissions have been reduced by approximately 90% through combination of industrial technological developments and legislated controls. Metal analysis in the present study revealed that the levels of copper and cobalt in soils from mining sites in the Lubumbashi (DR-Congo) were up to 200 fold higher compared to contaminated Sudbury sites and tailings. Zinc content in soil samples from some mining areas in Lubumbashi was at least 70 times higher compared to samples from the Sudbury area. Nickel content in soil samples from Lubumbashi were much lower compared to the Sudbury Region samples. Overall, this study confirms that the African Copper belt region is among the ten most polluted areas in the world.

Metal content in soil and black spruce (Picea mariana) trees in the Sudbury region (Ontario, Canada): low concentration of arsenic, cadmium, and nickel detected near smelter sources.

Several studies have reported high metal concentrations in soil within the vicinity of smelters in the Sudbury (Ontario) region. Continued investigation and monitoring of soil and vegetation are essential to the understanding of ecosystem recovery following the reduction of emissions from smelters and the establishment of a reforestation program. The concentrations of Cd, Co, Cu, Fe, Ni, and Zn, found in the present study were within the limits set by Ontario Ministry of Environment and Energy (OMEE) guidelines even in sites within the vicinity of the Falconbridge Smelters. The levels of these elements in black spruce (Picea mariana) tissues were much lower and far below the toxic levels for vegetation. This is the first documented report of metal content in black spruce populations in the Sudbury region.

From laboratory to Phase I/II cancer trials with recombinant biotherapeutics.

Many promising recombinant cancer medicines are generated by academic research and increasing the number of these products that are translated into the clinic will increase the pipeline of new therapies. Recombinant proteins for use in Phase I/II cancer trials must be produced to standards of Good Manufacturing Practice (GMP) in compliance with EU law. This can be a major obstacle for translating experimental products to clinical reality especially when there is no established process or prior experience with GMP. Here, we illustrate the principals of GMP with a step-by-step guide and we show that GMP can be achieved on a relatively small scale in the researchers own institution. The process is exemplified with an antibody-based therapeutic expressed in the yeast Pichia pastoris. The purified product has been used safely in patients and the principles are applicable to any recombinant protein required for Phase I/II cancer trials.

A comparative linkage map of oilseed rape and its use for QTL analysis of seed oil and erucic acid content.

We have developed a new DH mapping population for oilseed rape, named TNDH, using genetically and phenotypically diverse parental lines. We used the population in the construction of a high stringency genetic linkage map, consisting of 277 loci, for use in quantitative genetic analysis. A proportion of the markers had been used previously in the construction of linkage maps for Brassica species, thus permitting the alignment of maps. The map includes 68 newly developed Sequence Tagged Site (STS) markers targeted to the homologues of defined genes of A. thaliana. The use of these markers permits the alignment of our linkage map with the A. thaliana genome sequence. An additional 74 loci (31 newly developed STS markers and 43 loci defined by SSR and RFLP markers that had previously been used in published linkage maps) were added to the map. These markers increased the resolution of alignment of the newly constructed linkage map with existing Brassica linkage maps and the A. thaliana genome sequence. We conducted field trials with the TNDH population at two sites, and over 2 years, and identified reproducible QTL for seed oil content and erucic acid content. The results provide new insights into the genetic control of seed oil and erucic acid content in oilseed rape, and demonstrate the utility of the linkage map and population.

Tumour necrosis factor (TNFalpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma.

BACKGROUND: Tumour necrosis factor alpha (TNFalpha) is a major therapeutic target in a range of chronic inflammatory disorders characterised by a Th1 type immune response in which TNFalpha is generated in excess. By contrast, asthma is regarded as a Th2 type disorder, especially when associated with atopy. However, as asthma becomes more severe and chronic, it adopts additional characteristics including corticosteroid refractoriness and involvement of neutrophils suggestive of an altered inflammatory profile towards a Th1 type response, incriminating cytokines such as TNFalpha. METHODS: TNFalpha levels in bronchoalveolar lavage (BAL) fluid of 26 healthy controls, 42 subjects with mild asthma and 20 with severe asthma were measured by immunoassay, and TNFalpha gene expression was determined in endobronchial biopsy specimens from 14 patients with mild asthma and 14 with severe asthma. The cellular localisation of TNFalpha was assessed by immunohistochemistry. An open label uncontrolled clinical study was then undertaken in 17 subjects with severe asthma to evaluate the effect of 12 weeks of treatment with the soluble TNFalpha receptor-IgG1Fc fusion protein, etanercept. RESULTS: TNFalpha levels in BAL fluid, TNFalpha gene expression and TNFalpha immunoreative cells were increased in subjects with severe corticosteroid dependent asthma. Etanercept treatment was associated with improvement in asthma symptoms, lung function, and bronchial hyperresponsiveness. CONCLUSIONS: These findings may be of clinical significance in identifying TNFalpha as a new therapeutic target in subjects with severe asthma. The effects of anti-TNF treatment now require confirmation in placebo controlled studies.

Pharmacotherapy and airway remodelling in asthma?

Over the last few decades attention has largely focused on airway inflammation in asthma, but more recently it has been appreciated that there are important structural airway changes which have been grouped together under the term "airway remodelling". It is only now that questions have been asked about the impact of treatment on these structural changes. This review examines the nature of these structural airway changes, the mechanisms of their generation, their potential consequences, and what is known about the ability of anti-asthma treatments to modulate these changes.

Monocyte CD14 response following endotoxin exposure in cotton spinners and office workers.

BACKGROUND: Monocyte cell surface CD14 acts as the major lipopolysaccharide (LPS) binding structure, and as such is of interest in the etiology of LPS induced disease. METHODS: The objective was to assess change in monocyte cell surface CD14 and CD4+ CD25+ lymphocytes in a group of cotton workers exposed to LPS over a working week, and to compare this to changes in office workers. Twenty-five cotton workers and nine office workers were studied. Monocyte CD14 fluorescence was measured by flow cytometry, on samples taken pre-shift on a Monday morning (baseline/pre-exposure), and subsequently after 6 and 72 hr. The majority of cotton workers were exposed to at least 1 EU/m(3) of endotoxin over a working shift, and some highly exposed (between 100 and 400 EU/m(3)). RESULTS: After 6 hr of work in the mill, cotton workers developed a significant upregulation in CD14 in comparison to office workers (P = 0.016), whereas CD14 expression had returned to levels not significantly differing from the office workers at 72 hr after first work exposure (P = 0.426). CONCLUSIONS: We propose that CD14 expression on monocytes may help to determine the mechanism of action of lipopolysaccharide in producing respiratory ill health, and may ultimately play a role in monitoring the health effect associated with LPS exposure in the workplace.

Mechanisms of isocyanate sensitisation. An in vitro approach.

Although there is an abundance of clinical evidence which suggests that the inhalation of isocyanates can induce occupational asthma, the immunological basis for the disease is not understood. We have investigated immune cell responses to isocyanate using the cell line mono-mac-6, by measuring the production of hydrogen peroxide, and the expression of ICAM-1 following challenge with isocyanates and their corresponding amines. We observed an increase in the levels of intracellular peroxide, in addition to an upregulation of ICAM-1 expression (P<0.05), following cell stimulation with isocyanates, which was not apparent following stimulation with amines. From the results of this study we hypothesise that the production of reactive oxygen species (ROS) by monocytic cells at the site of exposure to an isocyanate may have two potential outcomes. The first is that the ROS may contribute to tissue damage at the site of inflammation, and then secondly, it is possible this production of hydrogen peroxide may also induce the upregulation of adhesion markers on monocytic cells, specifically ICAM-1, which may potentiate the infiltration and adhesion of cells at the site of inflammation.