Atmospheric degradation of reactive biogenic VOCs and their role in aerosol formation: modelling activities, laboratory experiments and field studies in different vegetation zones

Atmosphärische Aerosole beeinflussen die Energiebilanz der Erde durch Absorption und Streuung der einfallenden Sonnenstrahlung. Des Weiteren können sie sowohl als Wolkenkondensationskeime fungieren, als auch die menschliche Gesundheit beeinträchtigen (Fuzzi et al., 2006). Die Biosphäre ist eine permanente, große Quelle an atmosphärischem Aerosol. Sie produziert überwiegend organische Partikel, welche zu einem großen Teil durch oxidative Umwandlung der emittierten Vorläufersubstanzen entstehen (Kleindienst et al., 2007; Hu et al., 2008). In großen Waldgebieten kann auf diese Weise gebildetes sekundäres organisches Aerosol sogar den Hauptbestandteil der feinen Partikelmasse ausmachen (Kanakidou et al., 2005; Martin et al., 2010). In dieser Arbeit wurde die Rolle der hochreaktiven biogenen flüchtigen organischen Kohlenwasserstoffe in der Aerosolbildung untersucht. Nach einer erfolgreichen Optimierung der Probenaufarbeitung, der Synthese von Referenzsubstanzen zur Quantifizierung, der Durchführung mehrere Atmosphären-Simulationsexperimente und Modellrechnungen zur Aufklärung des atmosphärischen Abbaus von β Caryophyllen, wurde die Rolle von Terpenoxidationsprodukten bei der Bildung von sekundärem organischem Aerosol in verschiedenen Vegetationszonen untersucht. Über dem borealen Nadelwald gesammelte Aerosolproben wurden auf saure Terpenoxidationsprodukte untersucht. Die Monoterpenoxidationsprodukte wiesen die höchste Konzentration auf. Es wurde ein maximaler Beitrag der Terpene von 29 % zum gesamten organischen Aerosol abgeschätzt. Die Aerosolzusammensetzung wurde durch die Windgeschwindigkeit und durch die daraus resultierende Aufenthaltsdauer der Luftmassen über bewaldeten Gebieten sowie durch das Alter der gesammelten Luftmassen beeinflusst. Des Weiteren wurde ein Einfluss von Waldbränden auf die Aerosolzusammensetzung beobachtet. Über dem tropischen Regenwald gesammelte Aerosolproben wurden ebenfalls auf saure Terpenoxidationsprodukte untersucht. Obwohl auch hier die Monoterpenoxidationsprodukte den Hauptanteil ausmachten, war jedoch der Einfluß von Sesquiterpenoxidationsprodukten wesentlich höher als bei den Aerosolproben des borealen Nadelwaldes. Ebenfalls der abgeschätzte Beirag von Terpenen zum organischen Aerosol (mit Werten bis zu 63 %) war stark erhöht. Dies deutet auf eine überwiegend biogene Herkunft der feinen Partikel über dem tropischen Regenwald hin. Auch hier wurden Einflüsse der Windgeschwindigkeit auf die Aerosolzusammensetzung beobachtet. Schließlich wurden Aerosolproben aus einem gemischten Laub- und Nadelwald der gemäßigten Zone auf saure Terpenoxidationsprodukte untersucht. Die Monoterpenoxidationsprodukte wiesen eine wesentlich höhere Konzentration auf als die Sesquiterpenprodukte. Generell war der Beitrag biogener Vorläufer zum atmosphärischen feinen Aerosol jedoch gering. Der abgeschätze prozentuale Anteil der Terpene am organischen Aerosol betrug maximal 7 %. Dies deutet auf einen hohen anthropogenen und nur geringen biogenen Beitrag zur regionalen Aerosolbildung hin. Dennoch zeigten die sauren Terpenoxidationsprodukte stark ausgeprägte Jahresverläufe, welche abhängig von der jeweiligen Vorläufersubstanz deutlich voneinander variierten. Auch der Oxidationszustand der Terpenprodukte unterlag einem Jahreszyklus aufgrund der ebenfalls durch die Jahreszeiten variierenden Ozon und Hydroxylradikal Konzentrationen. Trotz der dominierenden Rolle der Monoterpenoxidationsprodukte in den Aerosolproben aller drei Vegetationszonen, stieg die Konzentration der Sesquiterpenoxidationsprodukte im sekundären organischen Aerosol unter bestimmten Bedingungen signifikant an und erreichte Maximalwerte von bis zu 10 % (gemischter Laub- und Nadelwald der gemäßigten Zone), 17 % (borealer Nadelwald) oder sogar 26 % (tropischer Regenwald) der totalen Konzentration der Monoterpenoxidationsprodukte.Atmospheric aerosols influence the earth’s climate through absorbing or scattering solar radiation. Furthermore, they can act as cloud condensation nuclei and affect human health (Fuzzi et al., 2006). The terrestrial biosphere is a continuous and major source of atmospheric aerosol, mainly of particulate organic matter from which a significant fraction is formed by oxidation of biogenic precursors (Kleindienst et al., 2007; Hu et al., 2008). In large forested areas secondary organic aerosol (SOA) can even increase to the major part of the fine aerosol mode (Kanakidou et al., 2005; Martin et al., 2010). This work investigated the role of high reactive volatile organic compounds emitted by terrestrial vegetation in formation of secondary organic aerosol. After optimizing the sample preparation, synthesizing reference compounds for quantification, conducting reaction chamber experiments and performing simulation model runs to improve and enlarge the knowledge about the degradation mechanism of β-caryophyllene, the role of terpene oxidation products in secondary organic aerosol formation over different vegetation zones was investigated. Aerosol samples representative for a boreal forest environment were analysed for their major carboxylic terpene oxidation products. The monoterpene oxidation products were the dominating species in the collected aerosol. The calculated contribution of terpene SOA to the total ambient organic aerosol mass reached values up to 29 %. The wind speed influenced the composition of the particulate phase, probably by affecting the residence times of the air masses over forested areas leading to changes in concentration of terpene oxidation products and their oxidation state. Furthermore, influences of forest fires, which occured during the field campaign, on the aerosol composition were detected due to long range transport. Aerosol samples representative for a tropical rainforest environment were analysed for their major carboxylic terpene oxidation products. Although monoterpene oxidation products were also the dominating species in the collected aerosol, sesquiterpene oxidation products played a more important role in SOA formation than in the boreal forest environment. Generally, terpene SOA contributed to a substantial higher extend (with calculated maximum values of 63 %) to the total ambient organic aerosol, indicating that biogenic emissions play a major role in fine particulate matter formation over tropical rainforest. Again, the wind speed influenced the aerosol composition over the tropical rainforest. Aerosol samples collected at a temperate rural site in Germany throughout one year were analysed for the major carboxylic terpene oxidation products. The monoterpene oxidation products were much more abundant in ambient aerosol than the sesquiterpene oxidation products. Generally, the terpene oxidation products showed about tenfold (in case of monoterpenes) or even about hundredfold (in case of sesquiterpenes) decreased concentrations in ambient aerosol compared to aerosol samples from the boreal or tropical forest. Also the calculated contribution of terpene SOA to ambient organic aerosol with a maximum value of 7 % was quite low, indicating that this area is probably much more influenced by anthropogenic instead of biogenic emissions. Nonetheless, the terpene oxidation products showed a significant annual pattern with a strong increase during late spring and also the oxidation state of the products varied throughout one year due to annual ozone and hydroxyl radical cycles. However, although the monoterpene oxidation products were the dominating terpene species in the collected aerosol from all three vegetation zones, the concentration of sesquiterpene oxidation products in ambient secondary organic aerosol increased significantly under special conditions, reaching maximum values of up to 10 % (temperate mixed coniferous forest), 17 % (boreal coniferous forest) or even 26 % (tropical rainforest) of the total monoterpene oxidation product concentration.118 Seite

Impact of Borderline Resectability in Pancreatic Head Cancer on Patient Survival: Biology Matters According to the New International Consensus Criteria

Background: International consensus criteria (ICC) have redefined borderline resectability for pancreatic ductal adenocarcinoma (PDAC) according to three dimensions: anatomical (BR-A), biological (BR-B), and conditional (BR-C). The present definition acknowledges that resectability is not just about the anatomic relationship between the tumour and vessels but that biological and conditional dimensions also are important. Methods: Patients’ tumours were retrospectively defined b

In-situ high-temperature EXAFS measurements on radioactive and air-sensitive molten salt materials

The development at the Delft University of Technology (TU Delft, The Netherlands) of an experimental set-up dedicated to high-temperature in situ EXAFS measurements of radioactive, air-sensitive and corrosive fluoride salts is reported. A detailed description of the sample containment cell, of the furnace design, and of the measurement geometry allowing simultaneous transmission and fluorescence measurements is given herein. The performance of the equipment is tested with the room-temperature measurement of thorium tetrafluoride, and the Th—F and Th—Th bond distances obtained by fitting of the EXAFS data are compared with the ones extracted from a refinement of neutron diffraction data collected at the PEARL beamline at TU Delft. The adequacy of the sample confinement is checked with a mapping of the thorium concentration profile of molten salt material. Finally, a few selected salt mixtures (LiF:ThF4) = (0.9:0.1), (0.75:0.25), (0.5:0.5) and (NaF:ThF4) = (0.67:0.33), (0.5:0.5) are measured in the molten state. Qualitative trends along the series are discussed, and the experimental data for the (LiF:ThF4) = (0.5:0.5) composition are compared with the EXAFS spectrum generated from molecular dynamics simulations

Feasibility, safety and preliminary efficacy of preoperative stereotactic radiotherapy on the future pancreatic neck transection margin to reduce the risk of pancreatic fistula after high-risk pancreatoduodenectomy (FIBROPANC):protocol for a multicentre, single-arm trial

INTRODUCTION: Postoperative pancreatic fistula (POPF) occurs in 25% of patients undergoing a high-risk pancreatoduodenectomy (PD) and is a driving cause of major morbidity, mortality, prolonged hospital stay and increased costs after PD. There is a need for perioperative methods to decrease these risks. In recent studies, preoperative chemoradiotherapy in patients with pancreatic ductal adenocarcinoma (PDAC) reduced the rate of POPF seemingly due to radiation-induced pancreatic fibrosis. However, patients with a high risk of POPF mostly have a non-pancreatic periampullary tumour and do not receive radiotherapy. Prospective studies using radiotherapy specifically to reduce the risk of POPF have not been performed. We aim to assess the safety, feasibility and preliminary efficacy of preoperative stereotactic radiotherapy on the future pancreatic neck transection margin to reduce the rate of POPF. METHODS AND ANALYSIS: In this multicentre, single-arm, phase II trial, we aim to assess the feasibility and safety of a single fraction of preoperative stereotactic radiotherapy (12 Gy) to a 4 cm area around the future pancreatic neck transection margin in patients at high risk of developing POPF after PD aimed to reduce the risk of grade B/C POPF. Adult patients scheduled for PD for malignant and premalignant periampullary tumours, excluding PDAC, with a pancreatic duct diameter ≤3 mm will be included in centres participating in the Dutch Pancreatic Cancer Group. The primary outcome is the safety and feasibility of single-dose preoperative stereotactic radiotherapy before PD. The most relevant secondary outcomes are grade B/C POPF and the difference in the extent of fibrosis between the radiated and non-radiated (uncinate margin) pancreas. Evaluation of endpoints will be performed after inclusion of 33 eligible patients. ETHICS AND DISSEMINATION: Ethical approval was obtained by the Amsterdam UMC's accredited Medical Research Ethics Committee (METC). All included patients are required to have provided written informed consent. The results of this trial will be used to determine the need for a randomised controlled phase III trial and submitted to a high-impact peer-reviewed medical journal regardless of the study outcome. TRIAL REGISTRATION NUMBER: NL72913 (Central Committee on Research involving Human Subjects Registry) and NCT05641233 (ClinicalTrials).</p

Norovirus outbreak in a natural playground: A One Health approach

Norovirus constitutes the most frequently identified infectious cause of disease outbreaks associated with untreated recreational water. When investigating outbreaks related to surface water, a One Health approach is insightful. Historically, there has been a focus on potential contamination of recreational water by bird droppings and a recent publication demonstrating human noroviruses in bird faeces suggested this should be investigated in future water-related norovirus outbreaks. Here, we describe a One Health approach investigating a norovirus outbreak in a natural playground. On social media, a large amount of waterfowl were reported to defecate near these playground premises leading to speculations about their potential involvement. Surface water, as well as human and bird faecal specimens, was tested for human noroviruses. Norovirus was found to be the most likely cause of the outbreak but there was no evidence for transmission via waterfowl. Cases had become known on social media prior to notification to the public health service underscoring the potential of online media as an early warning system. In view of known risk factors, advice was given for future outbreak investigations and natural playgroun

An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis

Background &amp; Aims: Patients with autoimmune hepatitis (AIH) almost invariably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of the current standard combination therapy of prednisolone and azathioprine. Mycophenolate mofetil (MMF) has emerged as an alternative option. The aim of this study was to compare MMF to azathioprine as induction therapy for AIH. Methods: In this 24-week, prospective, randomised, open-label, multicentre superiority trial, 70 patients with treatment-naive AIH received either MMF or azathioprine, both in combination with prednisolone. The primary endpoint was biochemical remission defined as normalisation of serum levels of alanine aminotransferase and IgG after 24 weeks of treatment. Secondary endpoints included safety and tolerability. Results: Seventy patients (mean 57.9 years [SD 14.0]; 72.9% female) were randomly assigned to the MMF plus prednisolone (n = 39) or azathioprine plus prednisolone (n = 31) group. The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% CI 4.0 to 46.7; p = 0.022). The MMF group exhibited higher complete biochemical response rates at 6 months (72.2% vs. 32.3%; p = 0.004). No serious adverse events occurred in patients who received MMF (0%) but serious adverse events were reported in four patients who received azathioprine (12.9%) (p = 0.034). Two patients in the MMF group (5.1%) and eight patients in the azathioprine group (25.8%) discontinued treatment owing to adverse events or serious adverse events (p = 0.018). Conclusions: In patients with treatment-naive AIH, MMF with prednisolone led to a significantly higher rate of biochemical remission at 24 weeks compared to azathioprine combined with prednisolone. Azathioprine use was associated with more (serious) adverse events leading to cessation of treatment, suggesting superior tolerability of MMF. Impact and implications: This randomised-controlled trial directly compares azathioprine and mycophenolate mofetil, both in combination with prednisolone, for the induction of biochemical remission in treatment-naive patients with autoimmune hepatitis. Achieving complete remission is desirable to prevent disease progression. Patients assigned to the mycophenolate mofetil group reached biochemical remission more often and experienced fewer adverse events. The findings in this trial may contribute to the re-evaluation of international guidelines for the standard of care in treatment-naive patients with autoimmune hepatitis. Trial registration number: #NCT02900443.</p

An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis

Background &amp; Aims: Patients with autoimmune hepatitis (AIH) almost invariably require lifelong immunosuppressive treatment. There is genuine concern about the efficacy and tolerability of the current standard combination therapy of prednisolone and azathioprine. Mycophenolate mofetil (MMF) has emerged as an alternative option. The aim of this study was to compare MMF to azathioprine as induction therapy for AIH. Methods: In this 24-week, prospective, randomised, open-label, multicentre superiority trial, 70 patients with treatment-naive AIH received either MMF or azathioprine, both in combination with prednisolone. The primary endpoint was biochemical remission defined as normalisation of serum levels of alanine aminotransferase and IgG after 24 weeks of treatment. Secondary endpoints included safety and tolerability. Results: Seventy patients (mean 57.9 years [SD 14.0]; 72.9% female) were randomly assigned to the MMF plus prednisolone (n = 39) or azathioprine plus prednisolone (n = 31) group. The primary endpoint was met in 56.4% and 29.0% of patients assigned to the MMF group and the azathioprine group, respectively (difference, 27.4 percentage points; 95% CI 4.0 to 46.7; p = 0.022). The MMF group exhibited higher complete biochemical response rates at 6 months (72.2% vs. 32.3%; p = 0.004). No serious adverse events occurred in patients who received MMF (0%) but serious adverse events were reported in four patients who received azathioprine (12.9%) (p = 0.034). Two patients in the MMF group (5.1%) and eight patients in the azathioprine group (25.8%) discontinued treatment owing to adverse events or serious adverse events (p = 0.018). Conclusions: In patients with treatment-naive AIH, MMF with prednisolone led to a significantly higher rate of biochemical remission at 24 weeks compared to azathioprine combined with prednisolone. Azathioprine use was associated with more (serious) adverse events leading to cessation of treatment, suggesting superior tolerability of MMF. Impact and implications: This randomised-controlled trial directly compares azathioprine and mycophenolate mofetil, both in combination with prednisolone, for the induction of biochemical remission in treatment-naive patients with autoimmune hepatitis. Achieving complete remission is desirable to prevent disease progression. Patients assigned to the mycophenolate mofetil group reached biochemical remission more often and experienced fewer adverse events. The findings in this trial may contribute to the re-evaluation of international guidelines for the standard of care in treatment-naive patients with autoimmune hepatitis. Trial registration number: #NCT02900443.</p

In situ high-temperature EXAFS measurements on radioactive and air-sensitive molten salt materials

The development at the Delft University of Technology (TU Delft, The Netherlands) of an experimental set-up dedicated to high-temperature in situ EXAFS measurements of radioactive, air-sensitive and corrosive fluoride salts is reported. A detailed description of the sample containment cell, of the furnace design, and of the measurement geometry allowing simultaneous transmission and fluorescence measurements is given herein. The performance of the equipment is tested with the room-temperature measurement of thorium tetrafluoride, and the Th-F and Th-Th bond distances obtained by fitting of the EXAFS data are compared with the ones extracted from a refinement of neutron diffraction data collected at the PEARL beamline at TU Delft. The adequacy of the sample confinement is checked with a mapping of the thorium concentration profile of molten salt material. Finally, a few selected salt mixtures (LiF:ThF4) = (0.9:0.1), (0.75:0.25), (0.5:0.5) and (NaF:ThF4) = (0.67:0.33), (0.5:0.5) are measured in the molten state. Qualitative trends along the series are discussed, and the experimental data for the (LiF:ThF4) = (0.5:0.5) composition are compared with the EXAFS spectrum generated from molecular dynamics simulations

Feasibility, safety and preliminary efficacy of preoperative stereotactic radiotherapy on the future pancreatic neck transection margin to reduce the risk of pancreatic fistula after high-risk pancreatoduodenectomy (FIBROPANC): protocol for a multicentre, single-arm trial

INTRODUCTION: Postoperative pancreatic fistula (POPF) occurs in 25% of patients undergoing a high-risk pancreatoduodenectomy (PD) and is a driving cause of major morbidity, mortality, prolonged hospital stay and increased costs after PD. There is a need for perioperative methods to decrease these risks. In recent studies, preoperative chemoradiotherapy in patients with pancreatic ductal adenocarcinoma (PDAC) reduced the rate of POPF seemingly due to radiation-induced pancreatic fibrosis. However, patients with a high risk of POPF mostly have a non-pancreatic periampullary tumour and do not receive radiotherapy. Prospective studies using radiotherapy specifically to reduce the risk of POPF have not been performed. We aim to assess the safety, feasibility and preliminary efficacy of preoperative stereotactic radiotherapy on the future pancreatic neck transection margin to reduce the rate of POPF. METHODS AND ANALYSIS: In this multicentre, single-arm, phase II trial, we aim to assess the feasibility and safety of a single fraction of preoperative stereotactic radiotherapy (12 Gy) to a 4 cm area around the future pancreatic neck transection margin in patients at high risk of developing POPF after PD aimed to reduce the risk of grade B/C POPF. Adult patients scheduled for PD for malignant and premalignant periampullary tumours, excluding PDAC, with a pancreatic duct diameter ≤3 mm will be included in centres participating in the Dutch Pancreatic Cancer Group. The primary outcome is the safety and feasibility of single-dose preoperative stereotactic radiotherapy before PD. The most relevant secondary outcomes are grade B/C POPF and the difference in the extent of fibrosis between the radiated and non-radiated (uncinate margin) pancreas. Evaluation of endpoints will be performed after inclusion of 33 eligible patients. ETHICS AND DISSEMINATION: Ethical approval was obtained by the Amsterdam UMC's accredited Medical Research Ethics Committee (METC). All included patients are required to have provided written informed consent. The results of this trial will be used to determine the need for a randomised controlled phase III trial and submitted to a high-impact peer-reviewed medical journal regardless of the study outcome. TRIAL REGISTRATION NUMBER: NL72913 (Central Committee on Research involving Human Subjects Registry) and NCT05641233 (ClinicalTrials)

Polymorphisms in transcription factor binding sites and enhancer regions and pancreatic ductal adenocarcinoma risk

Genome-wide association studies (GWAS) are a powerful tool for detecting variants associated with complex traits and can help risk stratification and prevention strategies against pancreatic ductal adenocarcinoma (PDAC). However, the strict significance threshold commonly used makes it likely that many true risk loci are missed. Functional annotation of GWAS polymorphisms is a proven strategy to identify additional risk loci. We aimed to investigate single-nucleotide polymorphisms (SNP) in regulatory regions [transcription factor binding sites (TFBSs) and enhancers] that could change the expression profile of multiple genes they act upon and thereby modify PDAC risk. We analyzed a total of 12,636 PDAC cases and 43,443 controls from PanScan/PanC4 and the East Asian GWAS (discovery populations), and the PANDoRA consortium (replication population). We identified four associations that reached study-wide statistical significance in the overall meta-analysis: rs2472632(A) (enhancer variant, OR 1.10, 95%CI 1.06,1.13, p = 5.5 × 10−8), rs17358295(G) (enhancer variant, OR 1.16, 95%CI 1.10,1.22, p = 6.1 × 10−7), rs2232079(T) (TFBS variant, OR 0.88, 95%CI 0.83,0.93, p = 6.4 × 10−6) and rs10025845(A) (TFBS variant, OR 1.88, 95%CI 1.50,1.12, p = 1.32 × 10−5). The SNP with the most significant association, rs2472632, is located in an enhancer predicted to target the coiled-coil domain containing 34 oncogene. Our results provide new insights into genetic risk factors for PDAC by a focused analysis of polymorphisms in regulatory regions and demonstrating the usefulness of functional prioritization to identify loci associated with PDAC risk.</p