Approaches to herbicide (MCPA) pollution mitigation in drinking water source catchments using enhanced space and time monitoring

Publication history: Accepted - 30 September 2020; Published online - 8 October 2020Freshwater occurrences of the selective acid herbicide 2-methyl-4-chloro-phenoxyacetic acid (MCPA) are an ongoing regulatory and financial issue for water utility industries as the number and magnitude of detections increase, particularly in surface water catchments. Assessments for mitigating pesticide pollution in catchments used as drinking water sources require a combination of catchment-based and water treatment solutions, but approaches are limited by a lack of empirical data. In this study, an enhanced spatial (11 locations) and temporal (7-hourly to daily sampling) monitoring approach was employed to address these issues in an exemplar surface water source catchment (384 km2). The spatial sampling revealed that MCPA was widespread, with occurrences above the 0.1 μg L−1 threshold for a single pesticide being highly positively correlated to sub-catchments with higher proportions of ‘Improved Grassland’ land use (r = 0.84). These data provide a strong foundation for targeting catchment-based mitigation solutions and also add to the debate on the ecosystems services provided by such catchments. Additionally, of the 999 temporal samples taken over 12 months from the catchment outlet, 25% were above the drinking water threshold of 0.1 μg L−1. This prevalence of high concentrations presents costly problems for source water treatment. Using these data, abstraction shutdowns were simulated for five scenarios using hydrometeorological data to explore the potential to avoid intake of high MCPA concentrations. The scenarios stopped abstraction for 4.2–9.3% of the April–October period and reduced intake of water containing over 0.1 μg L−1 of MCPA by 16–31%. This represents an important development for real-time proxy assessments for water abstraction in the absence of more direct pesticide monitoring data.This work was funded by the Source to Tap project (project reference IVA5018 – www.sourcetotap.eu). The Source to Tap project is supported by the European Union's INTERREG VA Programme, managed by the Special EU Programmes Body (SEUPB)

Evaluation of Chemcatcher® passive samplers for pesticide monitoring using high-frequency catchment scale data

Publication history: Accepted - 13 September 2022; Published online - 30 September 2022Passive samplers (PS) have been proposed as an enhanced water quality monitoring solution in rivers, but their performance against high-frequency data over the longer term has not been widely explored. This study compared the performance of Chemcatcher® passive sampling (PS) devices with high-frequency sampling (HFS: 7-hourly to daily) in two dynamic rivers over 16 months. The evaluation was based on the acid herbicides MCPA (2-methyl-4-chlorophenoxyacetic acid), mecoprop-P, fluroxypyr and triclopyr. The impact of river discharge parameters on Chemcatcher® device performance was also explored. Mixed effects modelling showed that time-weighted mean concentration (TWMC) and flow-weighted mean concentration (FWMC) values obtained by the HFS approach were both significantly higher (p 0.05). There was little indication that river flow parameters altered PS performance—some minor effects were not significant or consistent. Despite this, the PS recovery of very low concentrations indicated that Chemcatcher® devices may be used to evaluate the presence/absence and magnitude of acid herbicides in hydrologically dynamic rivers in synoptic type surveys where space and time coverage is required. However, a period of calibration of the devices in each river would be necessary if they were intended to provide a quantitative review of pesticide concentration as compared with HFS approaches.This work was funded in part by the Source to Tap project (project reference IVA5018 – http://www.sourcetotap.eu), supported by the European Union’s INTERREG VA Programme which is managed by the Special EU Programmes Body (SEUPB). The work was also part-funded by the FAIRWAY project (project reference 727984 - http://www.fair way-project.eu/). supported by the European Union’s HORIZON 2020 Programme

Quantifying MCPA load pathways at catchment scale using high temporal resolution data

peer-reviewedDetection of the agricultural acid herbicide MCPA (2-methyl-4-chlorophenoxyacetic acid) in drinking water source catchments is of growing concern, with economic and environmental implications for water utilities and wider ecosystem services. MCPA is poorly adsorbed to soil and highly mobile in water, but hydrological pathway processes are relatively unknown at the catchment scale and limited by coarse resolution data. This understanding is required to target mitigation measures and to provide a framework to monitor their effectiveness. To address this knowledge gap, this study reports findings from river discharge and synchronous MCPA concentration datasets (continuous 7 hour and with additional hourly sampling during storm events) collected over a 7 month herbicide spraying season. The study was undertaken in a surface (source) water catchment (384 km2—of which 154 km2 is agricultural land use) in the cross-border area of Ireland. Combined into loads, and using two pathway separation techniques, the MCPA data were apportioned into event and baseload components and the former was further separated to quantify a quickflow (QF) and other event pathways. Based on the 7 hourly dataset, 85.2 kg (0.22 kg km−2 by catchment area, or 0.55 kg km−2 by agricultural area) of MCPA was exported from the catchment in 7 months. Of this load, 87.7 % was transported via event flow pathways with 72.0 % transported via surface dominated (QF) pathways. Approximately 12 % of the MCPA load was transported via deep baseflows, indicating a persistence in this delayed pathway, and this was the primary pathway condition monitored in a weekly regulatory sampling programme. However, overall, the data indicated a dominant acute, storm dependent process of incidental MCPA loss during the spraying season. Reducing use and/or implementing extensive surface pathway disconnection measures are the mitigation options with greatest potential, the success of which can only be assessed using high temporal resolution monitoring techniques

Practical considerations for a TB controlled human infection model (TB-CHIM); the case for TB-CHIM in Africa, a systematic review of the literature and report of 2 workshop discussions in UK and Malawi

Background: Tuberculosis (TB) remains a major challenge in many domains including diagnosis, pathogenesis, prevention, treatment, drug resistance and long-term protection of the public health by vaccination. A controlled human infection model (CHIM) could potentially facilitate breakthroughs in each of these domains but has so far been considered impossible owing to technical and safety concerns. Methods: A systematic review of mycobacterial human challenge studies was carried out to evaluate progress to date, best possible ways forward and challenges to be overcome. We searched MEDLINE (1946 to current) and CINAHL (1984 to current) databases; and Google Scholar to search citations in selected manuscripts. The final search was conducted 3rd February 2022. Inclusion criteria: adults ≥18 years old; administration of live mycobacteria; and interventional trials or cohort studies with immune and/or microbiological endpoints. Exclusion criteria: animal studies; studies with no primary data; no administration of live mycobacteria; retrospective cohort studies; case-series; and case-reports. Relevant tools (Cochrane Collaboration for RCTs and Newcastle-Ottawa Scale for non-randomised studies) were used to assess risk of bias and present a narrative synthesis of our findings. Results: The search identified 1,388 titles for review; of these 90 were reviewed for inclusion; and 27 were included. Of these, 15 were randomised controlled trials and 12 were prospective cohort studies. We focussed on administration route, challenge agent and dose administered for data extraction. Overall, BCG studies including fluorescent BCG show the most immediate utility, and genetically modified Mycobacteria tuberculosis is the most tantalising prospect of discovery breakthrough. Conclusions: The TB-CHIM development group met in 2019 and 2022 to consider the results of the systematic review, to hear presentations from many of the senior authors whose work had been reviewed and to consider best ways forward. This paper reports both the systematic review and the deliberations

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Practical considerations for a TB controlled human infection model (TB-CHIM); the case for TB-CHIM in Africa, a systematic review of the literature and report of 2 workshop discussions in UK and Malawi [version 1; peer review: 2 approved, 1 approved with reservations]

Background: Tuberculosis (TB) remains a major challenge in many domains including diagnosis, pathogenesis, prevention, treatment, drug resistance and long-term protection of the public health by vaccination. A controlled human infection model (CHIM) could potentially facilitate breakthroughs in each of these domains but has so far been considered impossible owing to technical and safety concerns. Methods: A systematic review of mycobacterial human challenge studies was carried out to evaluate progress to date, best possible ways forward and challenges to be overcome. We searched MEDLINE (1946 to current) and CINAHL (1984 to current) databases; and Google Scholar to search citations in selected manuscripts. The final search was conducted 3rd February 2022. Inclusion criteria: adults ≥18 years old; administration of live mycobacteria; and interventional trials or cohort studies with immune and/or microbiological endpoints. Exclusion criteria: animal studies; studies with no primary data; no administration of live mycobacteria; retrospective cohort studies; case-series; and case-reports. Relevant tools (Cochrane Collaboration for RCTs and Newcastle-Ottawa Scale for non-randomised studies) were used to assess risk of bias and present a narrative synthesis of our findings. Results: The search identified 1,388 titles for review; of these 90 were reviewed for inclusion; and 27 were included. Of these, 15 were randomised controlled trials and 12 were prospective cohort studies. We focussed on administration route, challenge agent and dose administered for data extraction. Overall, BCG studies including fluorescent BCG show the most immediate utility, and genetically modified Mycobacteria tuberculosis is the most tantalising prospect of discovery breakthrough. Conclusions: The TB-CHIM development group met in 2019 and 2022 to consider the results of the systematic review, to hear presentations from many of the senior authors whose work had been reviewed and to consider best ways forward. This paper reports both the systematic review and the deliberations. Registration: PROSPERO (CRD42022302785; 21 January 2022)

Comprehensive review of safety in Experimental Human Pneumococcal Challenge.

IntroductionExperimental Human Pneumococcal Challenge (EHPC) involves the controlled exposure of adults to a specific antibiotic-sensitive Streptococcus pneumoniae serotype, to induce nasopharyngeal colonisation for the purpose of vaccine research. The aims are to review comprehensively the safety profile of EHPC, explore the association between pneumococcal colonisation and frequency of safety review and describe the medical intervention required to undertake such studies.MethodsA single-centre review of all EHPC studies performed 2011-2021. All recorded serious adverse events (SAE) in eligible studies are reported. An unblinded meta-analysis of collated anonymised individual patient data from eligible EHPC studies was undertaken to assess the association between experimental pneumococcal colonisation and the frequency of safety events following inoculation.ResultsIn 1416 individuals (median age 21, IQR 20-25), 1663 experimental pneumococcal inoculations were performed. No pneumococcal-related SAE have occurred. 214 safety review events were identified with 182 (12.85%) participants presenting with symptoms potentially in keeping with pneumococcal infection, predominantly in pneumococcal colonised individuals (colonised = 96/658, non-colonised = 86/1005, OR 1.81 (95% CI 1.28-2.56, P = DiscussionNo SAEs were identified directly relating to pneumococcal inoculation. Safety review for symptoms was infrequent but occurred more in experimentally colonised participants. Most symptoms were mild and resolved with conservative management. A small minority required antibiotics, notably those serotype 3 inoculated.ConclusionOutpatient human pneumococcal challenge can be conducted safely with appropriate levels of safety monitoring procedures in place

CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan

Heterogeneous subtypes of cancer-associated fibroblasts (CAFs) coexist within pancreatic cancer tissues and can both promote and restrain disease progression. Here, we interrogate how cancer cells harboring distinct alterations in p53 manipulate CAFs. We reveal the existence of a p53-driven hierarchy, where cancer cells with a gain-of-function (GOF) mutant p53 educate a dominant population of CAFs that establish a pro-metastatic environment for GOF and null p53 cancer cells alike. We also demonstrate that CAFs educated by null p53 cancer cells may be reprogrammed by either GOF mutant p53 cells or their CAFs. We identify perlecan as a key component of this pro-metastatic environment. Using intravital imaging, we observe that these dominant CAFs delay cancer cell response to chemotherapy. Lastly, we reveal that depleting perlecan in the stroma combined with chemotherapy prolongs mouse survival, supporting it as a potential target for anti-stromal therapies in pancreatic cancer