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The accumulation of gases into our atmosphere is a growing global concern that requires considerable quantification of the emission rates to mitigate the accumulation of gases in the atmosphere, especially the greenhouse gases (GHGs). In agriculture there are many sources of GHGs that require attention in order to develop practical mitigation strategies. Measuring these GHG sources often relies on highly technical instrumentation originally designed for applications outside of the emissions research in agriculture. Although the open-path laser (OPL) and open-path Fourier transform infrared (OP-FTIR) spectroscopic techniques are used in agricultural research currently, insight into their contributing error to emissions research has not been the focus of these studies. The objective of this study was to assess the applicability and performance (accuracy and precision) of OPL and OP-FTIR spectroscopic techniques for measuring gas mole fractions from agricultural sources. We measured the mole fractions of trace gases methane (CH4), nitrous oxide (N2O), and ammonia (NH3), downwind of point and area sources with a known release rate. The mole fractions measured by OP-FTIR and OPL were also input into models of atmospheric dispersion (WindTrax) allowing the calculation of fluxes. Trace gas release recoveries with WindTrax were examined by comparing the ratio of estimated and known fluxes. The OP-FTIR provided the best performance regarding stability of drift in stable conditions. The CH4 OPL accurately detected the low background (free-air) level of CH4; however, the NH3 OPL was unable to detect the background values ppbv. The dispersion modelling using WindTrax coupled with open-path measurements can be a useful tool to calculate trace gas fluxes from the well-defined source area.

In this study, we present the assimilation of data from the Orbiting Carbon Observatory-2 (OCO-2) (land nadir and glint data, version 9) to estimate the Australian carbon surface fluxes for the year 2015. To perform this estimation, we used both a regional-scale atmospheric transport–dispersion model and a four-dimensional variational assimilation scheme. Our results suggest that Australia was a carbon sink of −0.41 ± 0.08 PgC yr−1 compared to the prior estimate 0.09 ± 0.20 PgC yr−1 (excluding fossil fuel emissions). Most of the carbon uptake occurred in northern Australia over the savanna ecotype and in the western region over areas with sparse vegetation. Analysis of the enhanced vegetation index (EVI) suggests that the majority of the carbon uptake over the savanna ecosystem was due to an increase of vegetation productivity (positive EVI anomalies) amplified by an anomalous increase of rainfall in summer. Further from this, a slight increase of carbon uptake in Western Australia over areas with sparse vegetation (the largest ecosystem in Australia) was noted due to increased land productivity in the area caused by positive rainfall anomalies. The stronger carbon uptake estimate in this ecosystem was partially due to the land surface model (CABLE-BIOS3) underestimating the gross primary productivity of the ecosystem. To evaluate the accuracy of our carbon flux estimates from OCO-2 retrievals, we compare our posterior concentration fields against the column-averaged carbon retrievals from the Total Carbon Column Observing Network (TCCON) and ground-based in situ monitoring sites located around our domain. The validation analysis against TCCON shows that our system is able to reduce bias mainly in the summer season. Comparison with surface in situ observations was less successful, particularly over oceanic monitoring sites that are strongly affected by oceanic fluxes and subject to less freedom by the inversion. For stations located far from the coast, the comparison with in situ data was more variable, suggesting difficulties matching the column-integrated and surface data by the inversion, most likely linked to model vertical transport. Comparison of our fluxes against the OCO-2 model intercomparison (MIP) was encouraging. The annual carbon uptake estimated by our inversion falls within the ensemble of the OCO-2 MIP global inversions and presents a similar seasonal pattern.

When viewing scenes, observers differ in how long they linger at each fixation location and how far they move their eyes between fixations. What factors drive these differences in eye-movement behaviors? Previous work suggests individual differences in working memory capacity may influence fixation durations and saccade amplitudes. In the present study, participants (N = 98) performed two scene-viewing tasks, aesthetic judgement and memorization, while viewing 100 photographs of real-world scenes. Working memory capacity, working memory processing ability, and fluid intelligence were assessed with an operation span task, a memory updating task, and Raven’s Advanced Progressive Matrices respectively. Across participants, we found significant effects of task on both fixation durations and saccade amplitudes. At the level of each individual participant, we also found a significant relationship between memory updating task performance and participants’ fixation duration distributions. However, we found no effect of fluid intelligence and no effect of working memory capacity on fixation duration or saccade amplitude distributions, inconsistent with previous findings. These results suggest that the ability to flexibly maintain and update working memory is strongly related to fixation duration behavior.

Background Prompt and accurate diagnosis of lymphadenopathy is important, yet there is wide variability in clinical approach and referral patterns, leading to unnecessary investigations and delays in diagnosis. To address this, a lymph node diagnostic clinic (LNDC) was established at our tertiary referral center. Patients and Methods We retrospectively analyzed data from 320 consecutive patients referred to the LNDC from March 2008 to March 2020, to describe their management and outcomes. Results The most common diagnoses were reactive (57%) and malignant lymphadenopathy (28%). In those with reactive lymphadenopathy, 33% did not undergo further investigations, 37% underwent imaging only, and 29% underwent biopsy. For malignant lymphadenopathy, diagnosis was made at a median (interquartile range) of 9 (6-16) days from first LNDC review, with the decision to biopsy made at the first LNDC review in 95% of cases. Clinical features significantly associated with malignancy included age > 45, B symptoms, history of malignancy, and lymphadenopathy that was ≥ 2 cm, in multiple regions, bilateral, multiple nodes, or supraclavicular. At least 3 of these features were present in 88% of patients with malignant lymphadenopathy. Ultrasound had a sensitivity of 98% and negative predictive value of 97% for detecting malignant lymphadenopathy. Conclusion A dedicated LNDC in a tertiary referral center facilitates rapid assessment and diagnosis of lymphadenopathy through a risk-stratified model of management. Ultrasonography, as well as the presence of defined clinical risk factors, were most useful to differentiate benign from malignant lymphadenopathy.

Methane (CH4) is a potent greenhouse gas and a key precursor of tropospheric ozone, itself a powerful greenhouse gas and air pollutant. Methane emissions across Queensland's Surat Basin, Australia, result from a mix of activities, including the production and processing of coal seam gas (CSG). We measured methane concentrations over 1.5 years from two monitoring stations established 80 km apart on either side of the main CSG belt located within a study area of 350 km × 350 km. Using an inverse modelling approach coupled with a bottom-up inventory, we quantify methane emissions from this area. The inventory suggests that the total emission is 173.2 × 106 kg CH4 yr−1, with grazing cattle contributing about half of that, cattle feedlots ∼ 25 %, and CSG processing ∼ 8 %. Using the inventory emissions in a forward regional transport model indicates that the above sources are significant contributors to methane at both monitors. However, the model underestimates approximately the highest 15 % of the observed methane concentrations, suggesting underestimated or missing emissions. An efficient regional Bayesian inverse model is developed, incorporating an hourly source–receptor relationship based on a backward-in-time configuration of the forward regional transport model, a posterior sampling scheme, and the hourly methane observations and a derived methane background. The inferred emissions obtained from one of the inverse model setups that uses a Gaussian prior whose averages are identical to the gridded bottom-up inventory emissions across the domain with an uncertainty of 3 % of the averages best describes the observed methane. Having only two stations is not adequate at sampling distant source areas of the study domain, and this necessitates a small prior uncertainty. This inverse setup yields a total emission of (165.8 ± 8.5) × 106 kg CH4 yr−1, slightly smaller than the inventory total. However, in a subdomain covering the CSG development areas, the inferred emissions are (63.6 ± 4.7) × 106 kg CH4 yr−1, 33 % larger than those from the inventory. We also infer seasonal variation of methane emissions and examine its correlation with climatological rainfall in the area.

PURPOSE: Patients with indolent non-Hodgkin lymphoma (iNHL) undergo regular active surveillance in between treatment periods to detect disease relapse or progression. As part of surveillance, international guidelines recommend regular routine blood testing, which is based on consensus rather than evidence of utility. METHODS: We conducted a retrospective analysis of all patients older than age 16 years diagnosed with grade 1-3A follicular or marginal zone lymphoma between 2008 and 2017 from 2 Australian cancer centers to assess the utility of full blood examination, lactate dehydrogenase, and β2-microglobulin in detecting progression events, defined as either disease relapse or progression of disease. RESULTS: One hundred eighty patients attended 1,757 outpatient appointments (median follow-up, 36 months). Routine blood tests (RBTs) were performed before 83% of appointments. Seventy-four progression events occurred in 62 patients. Only 2 events (3%) were detected by RBTs alone, both of which occurred in treatment-naïve patients who subsequently developed symptoms within 3 weeks. The remainder of progression events were suspected clinically (88%) or detected by imaging (9%). RBT results were frequently abnormal in asymptomatic patients (19%), with abnormal results leading to either additional investigations or an increased surveillance frequency in 8% of cases. The overall sensitivity and positive predictive value of abnormal RBT results in detecting progression events were 39% and 9%, respectively. CONCLUSION: RBTs have poor performance characteristics and rarely detect clinically significant disease progression or relapse in asymptomatic patients with iNHL.

Anthropogenic activities, particularly fertilisation, have resulted in significant increases in nitrogen in soils globally, leading to negative environmental impacts including eutrophication, acidification, poor air quality, and emissions of the important greenhouse gas N2O. Potential changes in terrestrial N loss pathways driven by global change and spatial redistribution of N inputs are highly uncertain. We present a novel coupled soil-atmosphere isotope model (IsoTONE; ISOtopic Tracing Of Nitrogen in the Environment) to quantify terrestrial N losses and N2O emissions and emission factors for the period 1850-2020. The soil module is initialised using a global isoscape of natural soil δ15N values generated from measurement data using an artificial neural network. The model is optimized within a Bayesian framework using a high precision tropospheric time series of N2O isotopic composition as well as emission factor measurements from many sites across the globe.N inputs from atmospheric deposition caused the majority (51%; 3.6±0.3 Tg N2O-N a-1) of total anthropogenic N2O emissions from soils (7.1±0.9 Tg N2O-N a-1) in 2020. Growth in total and anthropogenic soil N2O emissions over the past century was driven by both fertilization and deposition, however N inputs from biological fixation were responsible for subdecadal variability in emissions. N2O emission factors show large spatial variability due to climate and soil parameters. The mean global EF for N2O weighted by N inputs was 4.3±0.3% in 2020, much higher than the land surface area-weighted mean of 1.1±0.1%, as a large proportion of N inputs were in regions with relatively high emission factors. Climate warming as well as redistribution of fertilisation inputs have led to an increase in global EF for N2O over the past century; these additional emissions account for 18% of the total anthropogenic soil flux in 2020. Predicted increases in fertilisation in emerging economies will accelerate N2O-driven climate warming in the coming decades, unless targeted mitigation measures focussing on fertiliser management in developing regions are introduced.

Anthropogenic nitrogen inputs cause major negative environmental impacts, including emissions of the important greenhouse gas N2O. Despite their importance, changes in terrestrial N loss pathways driven by global change and spatial redistribution of N inputs are highly uncertain. We present a novel coupled soil-atmosphere isotope model (IsoTONE) to quantify terrestrial N losses and N2O emission factors from 1850-2020, initialised using a global dataset of natural soil δ15N, and optimized with a tropospheric timeseries of N2O isotopic composition using a Bayesian framework. N inputs from atmospheric deposition caused the majority (51%) of anthropogenic N2O emissions from soils in 2020. Long-term growth in emissions was driven by fertilization and deposition, however biological fixation caused subdecadal variability in emissions. N2O emission factors (EF) show large spatial variability due to climate and soil parameters. The mean effective global EF for N2O (weighted by N inputs) was 4.3±0.3% in 2020, much higher than the land surface area-weighted mean (1.1±0.1%). Climate change and redistribution of fertilisation have driven an increase in global EF over the past century, which accounts for 18% of the anthropogenic soil flux in 2020. Predicted increases in fertilisation in emerging economies will accelerate N2O-driven climate warming in coming decades, unless targeted mitigation measures focussing on fertiliser management and reduced N deposition are introduced.

The accumulation of gases into our atmosphere is a growing global concern that requires considerable quantification of the emission rates and mitigate the accumulation of gases in the atmosphere, especially the greenhouse gases (GHG). In agriculture there are many sources of GHG that require attention in order to develop practical mitigation strategies. Measuring these GHG sources often rely on highly technical instrumentation originally designed for applications outside of the emissions research in agriculture. Although the open-path laser (OPL) and open-path Fourier transform infrared (OP-FTIR) spectroscopic techniques are used in agricultural research currently, insight into their contributing error to emissions research has not been the focus of these studies. The objective of this study was to assess the applicability and performance (accuracy and precision) of OPL and OP-FTIR spectroscopic techniques for measuring gas concentration from agricultural sources. We measured the mixing ratios of trace gases methane (CH4), nitrous oxide (N2O), and ammonia (NH3), downwind of point and area sources with known release rates. The OP-FTIR provided the best performance regarding stability of drift in stable conditions. The CH4 OPL accurately detected the low background (free-air) level of CH4; however, the NH3 OPL was unable to detect the background values < 10 ppbv.

First-line tyrosine kinase inhibitors are standard of care for non-small-cell lung cancers (NSCLC) harbouring an epidermal growth factor receptor mutation, anaplastic lymphoma kinase fusion or c-ros oncogene 1 rearrangement. Other targetable oncogenic drivers have been identified but testing for these is neither funded nor commonly performed in Australia. Using a case example, we discuss the importance of considering several other genomic aberrations in our population, such as rearrangements in the RET proto-oncogene, which occur in 1-2% of lung adenocarcinoma. New oncogenic drivers and corresponding targeted agents are constantly being discovered; these will continue to refine the treatment of non-small-cell lung cancer in the era of precision medicine.

When viewing scenes, observers differ in how long they linger at each fixation location and how far they move their eyes between fixations. What factors drive these differences in eye-movement behaviors? Previous work suggests individual differences in working memory capacity may influence fixation durations and saccade amplitudes. In the present study, participants (N = 98) performed two scene-viewing tasks, aesthetic judgment and memorization, while viewing 100 photographs of real-world scenes. Working memory capacity, working memory processing ability, and fluid intelligence were assessed with an operation span task, a memory updating task, and Raven's Advanced Progressive Matrices, respectively. Across participants, we found significant effects of task on both fixation durations and saccade amplitudes. At the level of each individual participant, we also found a significant relationship between memory updating task performance and participants' fixation duration distributions. However, we found no effect of fluid intelligence and no effect of working memory capacity on fixation duration or saccade amplitude distributions, inconsistent with previous findings. These results suggest that the ability to flexibly maintain and update working memory is strongly related to fixation duration behavior.

The Southern Ocean plays an important role in determining atmospheric carbon dioxide (CO2), yet estimates of air-sea CO2 flux for the region diverge widely. In this study, we constrained Southern Ocean air-sea CO2 exchange by relating fluxes to horizontal and vertical CO2 gradients in atmospheric transport models and applying atmospheric observations of these gradients to estimate fluxes. Aircraft-based measurements of the vertical atmospheric CO2 gradient provide robust flux constraints. We found an annual mean flux of –0.53 ± 0.23 petagrams of carbon per year (net uptake) south of 45°S during the period 2009–2018. This is consistent with the mean of atmospheric inversion estimates and surface-ocean partial pressure of CO2 (PCO2)–based products, but our data indicate stronger annual mean uptake than suggested by recent interpretations of profiling float observations.

BACKGROUND Current guidelines recommend a step-wise screening algorithm for all colorectal carcinomas (CRC) to identify patients with Lynch syndrome (LS). AIM To describe the frequencies of mismatch repair deficiency (dMMR), BRAFV600E mutations and MLH1 methylation in resected CRC, and evaluate the impact of universal screening on LS detection. METHODS Retrospectively, 1171 consecutive cases of resected CRC were identified between 2010 and 2017 from a large multi-centre pathology service. Testing for dMMR by immunohistochemistry (IHC) was initiated by the reporting pathologist from 2010, until universal testing was introduced in 2015. Patients with dMMR were referred to the Family Cancer Clinic (FCC) for consideration of germline mutation analysis. RESULTS IHC was performed on 680 tumours, with abnormal expression in 124 (18%). Referral to FCC was made for 44 of the 88 patients with abnormal IHC (excluding those with BRAFV600E mutations). Of the 29 who attended, 16 underwent germline genetic testing, and LS was diagnosed in 7 with a germline mutation. After implementation of universal testing, there was a greater incidence of dMMR (17% vs 10%, P = 0.02), rate of BRAFV600E testing (79% vs 25%, P

Elderly patients may be heterogeneous in their abilities to tolerate immunochemotherapy-associated toxicities. We describe the morbidity of rituximab-chemotherapy combinations among 205 newly-diagnosed diffuse large B-cell lymphoma (DLBCL) patients aged ≥60 years from 3 tertiary hospitals between 2009 and 2016, and explore the utility of retrospectively-assigned baseline Comprehensive Geriatric Assessment (CGA) in predicting these toxicities. Seventy-three percent (146/201) experienced grade ≥3 toxicities, 81% (163/201) needed admission, 52% (107/205) had ≥2 unplanned admissions, 82/201 (41%) required dose reductions (DR) subsequent to Cycle 1, 39/166 (23%) had chemotherapy delays and 26/198 (13%) ceased therapy early. CGA was associated with pre-emptive baseline DR and perhaps because of this, did not predict grade ≥3 toxicities, ≥2 unplanned admissions or subsequent DR. Three-year overall survival (OS) of CGA-fit, CGA-unfit and CGA-frail patients was 82%, 60% and 53%, respectively. Three-year progression-free survival (PFS) of CGA-fit, CGA-unfit and CGA-frail patients was 66%, 58% and 46%, respectively. OS of CGA-fit patients was not statistically different from CGA-unfit patients, but was superior to CGA-frail patients (hazard ratio 2·892, 95% confidence interval 1·275-6·559, P = 0·011). PFS differences were not statistically significant. Baseline DR and early therapy cessation were associated with inferior OS and PFS independent of CGA. Prospective studies are needed to confirm if CGA-adapted treatment strategies minimize morbidity and improves survival.

Oceans cover over 70 % of the Earth's surface. Ship-based measurements are an important component in developing an understanding of atmosphere of this vast region. A common problem that impacts the quality of atmospheric data collected from marine research vessels is exhaust from both diesel combustion and waste incineration from the ship itself. Described here is an algorithm, developed for the recently commissioned Australian blue-water research vessel (RV) Investigator, that identifies exhaust periods in sampled air. The RV Investigator, with two dedicated atmospheric laboratories, represents an unprecedented opportunity for high-quality measurements of the marine atmosphere. The algorithm avoids using ancillary data such as wind speed and direction, and instead utilises components of the exhaust itself – aerosol number concentration, black carbon concentration, and carbon monoxide and carbon dioxide mixing ratios. The exhaust signal is identified within each of these parameters individually before they are combined and an additional window filter is applied. The algorithm relies heavily on statistical methods, rather than setting thresholds that are too rigid to accommodate potential temporal changes. The algorithm is more effective than traditional wind-based filters in removing exhaust data without removing exhaust-free data, which commonly occurs with traditional filters. In application to the current dataset, the algorithm identifies 26 % of the wind filter's “clean” data as exhaust, and recovers 5 % of data falsely removed by the wind filter. With suitable testing, the algorithm has the potential to be applied to other ship-based atmospheric measurements where suitable measurements exist.

Background: Leptomeningeal spread in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor ( EGFR ) mutations who experience disease progression on TKIs portends a poor prognosis. Mutation profiling of tumour DNA in cerebrospinal fluid (CSF) samples can be used to determine the presence of the EGFR T790M resistance mutation, indicating that osimertinib, a CNS-penetrating 3 rd generation TKI may be efficacious. Methods: Eight patients on EGFR TKIs who progressed with cytology-proven leptomeningeal disease at our institution were studied. EGFR mutations were profiled in CSF using droplet digital PCR (ddPCR) and compared to matched plasma samples. Clinical characteristics and survival outcomes on subsequent therapies tailored to ddPCR analysis were reported. Results: None of the four patients who developed leptomeningeal disease while receiving 1st generation EGFR TKIs developed the EGFR T790M mutation in CSF. One patient who did not have extra-cranial disease and was EGFR T790M-negative in both plasma and CSF was nevertheless treated with standard-dose osimertinib, and achieved a rapid and durable response lasting 9 months to date. Three patients developed leptomeningeal disease on osimertinib, with one patient developing the EGFR C797S mutation in a cis-allelic conformation with the EGFR T790M mutation in plasma. Conclusions: Standard-dose osimertinib resulted in a clinically meaningful response in a patient with EGFR T790M-negative 1st generation EGFR TKI refractory leptomeningeal disease. Next generation sequencing and ddPCR has a role at identifying the C797S mutation and its allelic conformation with the T790M mutation with clinical implications.

Anthropogenic activities, particularly fertilisation, have resulted in significant increases in reactive nitrogen (rN) in soils globally, leading to eutrophication, acidification, poor air quality, and emissions of the important greenhouse gas N2O. Understanding the partitioning of rN losses into different environmental compartments is critical to mitigate negative impacts, however, loss pathways are poorly quantified, and potential changes driven by climate warming and societal shifts are highly uncertain. We present a coupled soil-atmosphere isotope model (IsoTONE; ISOtopic Tracing Of Nitrogen in the Environment) to partition rN losses into leaching, harvest, NH3 volatilization, and production of NO, N2 and N2O based on a global dataset of soil δ15N, as well as numerous other geoclimatic and experimental datasets. The model was optimized in a Bayesian framework using a time series of N2O mixing ratios and isotopic compositions since the preindustrial era, as well as a global dataset of N2O emission factors (EF). The posterior model results showed that the total anthropogenic flux in 2020 (7.8 Tg N2O-N a-1) was dominated by indirect emissions resulting from N deposition, while the growth rate and trend in anthropogenic N2O was driven by both direct N fertilisation and deposition inputs. In contrast, inputs from fixation N drive natural N2O emissions, and were responsible for subdecadal interannual variability in total emissions.Total N gas (N2O + NO + N2) production and N2O losses were strongly dependent on geoclimate and thus spatially variable, therefore the spatial pattern of N inputs strongly impacted resulting EFs and total N2O emissions. The area-weighted global EF for N2O was 1% of anthropogenic N inputs in 2020, similar to the current IPCC default of 1.4%, however the N input-weighted global EF was 4.3%. Shifts in fertilisation inputs from the temperate Northern hemisphere towards warmer regions with higher EFs such as India and China have led to accelerating N2O emissions (1.02±0.7 Tg N2O-N a-1). In addition, N2O emissions have increased over the past decades due to climate warming (0.76±0.4 Tg N2O-N a-1). Predicted increases in fertilisation in India and Africa in the coming decades could further accelerate N2O-driven climate warming, unless mitigation measures are implemented to increase fertiliser N use efficiency and reduce N2O emission factors.

Environmental contextChlorofluorocarbons (CFCs) are potent greenhouse and stratospheric ozone depleting trace gases. Their atmospheric concentrations are in decline, thanks to global production and consumption controls imposed by the Montreal Protocol. In recent years, the rates of decline of CFC atmospheric concentrations, especially for CFC-11 (CCl3F), are not as large as anticipated under the Protocol, resulting in renewed efforts to estimate CFC consumption and/or emissions to possibly identify new or poorly quantified sources. AbstractAustralian emissions of chlorofluorocarbons (CFCs) have been estimated from atmospheric CFC observations by both inverse modelling and interspecies correlation techniques, and from CFC production, import and consumption data compiled by industry and government. Australian and global CFC emissions show similar temporal behaviour, with emissions peaking in the late-1980s and then declining by ~10% per year through to the present. Australian CFC emissions since 1978 account for less than 1% of global emissions and therefore make a correspondingly small contribution to stratospheric ozone depletion. The current CFC emissions in Australia are likely from ‘banks’ of closed-cell foams, and refrigeration–air conditioning equipment now more than 20 years old. There is no evidence of renewed consumption or emissions of CFCs in Australia. The reduction in CFC emissions has made a significant contribution to reducing Australian greenhouse gas emissions.

Methane (CH4) is the second most important anthropogenic greenhouse gas after carbon dioxide (CO2) in the atmosphere1. Human activities are estimated to contribute ~50% of total CH4 emissions globally2. With 68% of the population projected to live in urban areas by 20503, there is a need to better quantify CH4 emissions from urban sources and to develop mitigation plans. Major potential urban sources include: the gas distribution network, landfills, the sewerage network, appliances in houses (heaters, stoves, hot-water systems), wood burning heaters, and urban wetlands.This study aimed to determine the major CH4 sources in Melbourne (Australia’s second largest city with a population approaching 5 million people). Melbourne has grown rapidly since it was founded ~200 years ago and this has left legacy potential CH4 sources. For example, the gas distribution system has piping ranging from modern to 100 years old (common in unrenovated houses from early last century); landfills that use to be on the city fringe are now surrounded by new housing developments. To map the location of major CH4 sources throughout Melbourne we conducted a mobile survey, measuring the CH4 mole fraction ([CH4]) at a height of 3 m using a Los Gatos Research ultra-portable greenhouse gas analyser. An air inlet was attached to the roof of the car and the location of the measurements were georeferenced using a Hemisphere GPS system as we drove around the city. The day and night-time surveys were undertaken from the 26th – 27th July 2019 (winter). When a major CH4 plume was detected 10 air samples were collected and stored 3 litre FlexFoil bags. These samples were analysed for [CH4], δ13C-CH4, [CO2], δ13C-CO2 using a Picarro G2201-i cavity ring-down spectrometer (CRDS). To determine the δ13C-CH4 signature of the plume each set of bags was analysed using a Miller-Tans plot and Bayesian regression. The combination of potential observable sources and the δ13C-CH4 signature was then used to attribute the source of the CH4 plume. We show that the δ13C-CH4 signatures of the CH4 plumes are needed to reduce the risk of attributing a plume to the wrong source. We present an example of separating domestic wood fires from a ‘super-emitter’ leak from the gas distribution system, and we also show how we traced a landfill plume for a distance of over 5 km using δ13C-CH4 measurements.Our research demonstrates that mobile [CH4] surveys coupled with δ13C-CH4 analyses is a cost-effective workflow for mapping both diffuse CH4 emissions and ‘super-emitters’. Such surveys could be systematically undertaken in cities worldwide to delineate and prioritise targets for CH4 emission reduction. References(1) Myhre, G. et al. Cambridge University Press, 2013; Vol. 9781107057, pp 659–740.(2) Saunois, M. et al. Earth Syst. Sci. Data Discuss. 2019, 1–138.(3) United Nations. World Urbanization Prospects The 2018 Revision (ST/ESA/SER.A/420). 2019.

There is a paucity of data regarding the utility of routine urine cultures in adults with febrile neutropenia (FN) without urinary symptoms receiving protocolised antibiotics. This is reflected by inconsistent recommendations in international and regional FN guidelines. We addressed this issue by retrospectively reviewing the impact of routine urine cultures on antibiotic management in haematology cancer inpatients at a tertiary hospital. All haematology inpatients over a 5-year period (2011–2015) were retrospectively reviewed for episodes of FN (neutrophil count 37.5 °C). For each episode, demographic data, urinary tract symptoms and signs (absence of which was termed ‘asymptomatic’), urinalysis and urine culture results, antibiotic therapy and duration, and patient outcomes were collected. A urine culture was considered positive if > 105 colony forming units (CFU)/L were detected. Empiric antibiotic therapy for FN consisted of intravenous piperacillin/tazobactam in stable patients, with the addition of vancomycin and a single dose of gentamicin if systemically compromised. Four hundred and thirty-three episodes of FN were identified in 317 patients. Urine cultures were performed in 362 (84%) episodes. Cultures were positive in 9 of 48 (19%) symptomatic episodes versus 8 of 314 (2.5%) asymptomatic episodes (RR = 7.4, p

BACKGROUND: Anti-HER2 therapy-related cardiotoxicity is well described in the context of clinical trials, particularly in the setting of early stage disease, but there is more limited data in advanced breast cancer and in the real world setting. MATERIAL AND METHODS: A prospectively-maintained registry database with 312 consecutive patients diagnosed with HER2 positive advanced breast cancer in Australia was analysed. RESULTS: 287 patients (92%) received anti-HER2 therapy, 17 (6%) experienced anti-HER2 therapy-related cardiotoxicity. Patients who experienced cardiotoxicity were more likely to have ≥2 risk factors for cardiotoxicity (OR 3.9 95% CI 1.4-11.3 p = 0.01). A prior diagnosis of cardiovascular disease was significantly associated with cardiotoxicity (OR 7.1 95% CI 1.3-39.5). Cardiotoxicity resolved on imaging in 65% of patients; there was no association between severity and resolution. 11 patients (65%) received cardiologist input. Of the patients who developed cardiotoxicity, 12 patients (71%) received further anti-HER2 therapy in the first- or second-line setting without recurrent cardiotoxicity. DISCUSSION AND CONCLUSION: Therapy-related cardiotoxicity is an uncommon complication of anti-HER2 therapy in the real world setting. Cardiac toxicity resolved in the majority of affected patients, and further anti-HER2 therapy was administered without recurrence of cardiac issues. Our data suggests anti-HER2 therapy can be safely given in routine care, even in patients with risk factors for toxicity.

Background Patients with aggressive lymphoma achieving complete remission (CR) after first-line combination chemotherapy undergo regular surveillance to detect relapse. Current international guidelines recommend routine follow-up blood tests in this context, but evidence supporting this practice is limited. Methods We conducted a multi-centre retrospective analysis of all patients diagnosed with aggressive lymphoma treated with curative-intent chemotherapy who achieved CR for at least 3 months between 2000 and 2015. An abnormal blood test was defined as any new and unexplained abnormality for full blood examination, lactate dehydrogenase or erythrocyte sedimentation rate. Results Three hundred and forty-six patients attended a total of 3084 outpatient visits; blood tests were performed at 90% of these appointments. Fifty-six (16%) patients relapsed. Routine laboratory testing detected relapse in only three patients (5% of relapses); in the remaining patients, relapse was suspected clinically (80%) or detected by imaging (15%). The sensitivity of all blood tests was 42% and the positive predictive value was 9%. No significant difference in survival was shown in patients who underwent a routine blood test within 3 months prior to relapse versus those who did not (p = 0.88). Conclusions Routine blood tests demonstrate unacceptably poor performance characteristics, have no impact on survival and thus have limited value in the detection of relapse in routine surveillance.

BACKGROUND: Routine chest X-ray (CXR) is recommended for neutropenic fever (NF) management however its role is relatively understudied in haematology patients. AIM: To investigate the utility of CXR in the diagnosis and management of patients with haematological conditions complicated by NF. METHODS: Retrospective, single-centre analysis of haematology patients admitted with NF between January 2011 and December 2015. Baseline demographics, treatment details and outcomes were collected from electronic patient records. CXR underwent independent radiology review. Primary endpoints were a proportion of NF episodes in which CXR detected a probable chest infection in the absence of respiratory symptoms/signs and/or resulted in a change in antibiotic management. RESULTS: Four hundred and thirty-five episodes were identified; CXR was performed in 75% of patients (65% within 2 days of NF). In 4 of 164 (2.4%) asymptomatic patients, CXR was consistent with infection, in contrast to 19 of 119 (16%) patients with clinical signs of respiratory infection. Only 3 of 283 (1.1%) CXR resulted in a change to antibiotics. CXR consistent with infection was not associated with increased mortality or increased admission length, although there was an association with intensive care unit admission (odds ratios: 7.61, 95% confidence interval: 2.04-28.31). CONCLUSION: In haematology patients with NF, CXR rarely detected chest infection or changed management in patients with no respiratory symptoms or signs. CXR in our institution is no longer part of routine assessment of NF in the absence of these features.

To describe the incidence of infective endocarditis (IE) detected on echocardiography in cancer patients with confirmed Staphylococcus aureus bacteraemia (SAB). We retrospectively identified 95 cases of SAB in cancer patients from January 2007–March 2016. Echocardiography was ordered at the discretion of the treating team, and positive findings defined according to the Modified Duke Criteria. Complicated bacteraemia was defined by prolonged bacteraemia, presence of intracardiac device/prosthetic valve, or signs of metastatic infection. Major predisposing risk factors for IE (intracardiac device, prosthetic valve, valvular disease, diabetes mellitus, renal dialysis) were present in 27% of cases. Fifty-one of 95 (54%) had a central venous catheter and 17 (18%) patients had complicated bacteraemia. Echocardiography was performed in 75/95 (79%) episodes, with transthoracic echocardiography (TTE) alone in 56, transoesophageal echocardiography (TOE) alone in 4 and both in 15. Echocardiography was diagnostic for IE in 2 patients (1 TTE, 1 TOE), including one result that led to the diagnosis of IE in a clinically unsuspected case. Four further cases of IE were diagnosed on clinical findings, resulting in an overall rate of IE of 6% (6/95). Five of these cases occurred in patients with complicated bacteraemia or ≥ 1 risk factor for IE. No patient was readmitted due to IE. IE is infrequent in cancer patients with uncomplicated SAB and no risk factors for IE. Performing echocardiography routinely in all cancer patients with SAB rarely alters diagnosis or affects antibiotic management and therefore should be reserved for patients with specific risk factors.

The role ships play in atmospheric, oceanic, and biogeochemical observations is described with a focus on measurements made within 100 m of the ocean surface. Ships include merchant and research vessels, cruise liners and ferries, fishing vessels, coast guard, military, and other government-operated ships, yachts, and a growing fleet of automated surface vessels. The present capabilities of ships to measure essential climate/ocean variables and the requirements from a broad community to address operational, commercial, and scientific needs are described. Following the guidance from the OceanObs'19 organizing committee, the authors provide a vision to expand observations needed from ships to understand and forecast the exchanges across the ocean-atmosphere interface. The vision addresses (1) recruiting vessels to improve both spatial and temporal sampling, (2) conducting multi-variate sampling on ships, (3) raising technology readiness levels of automated shipboard sensors and ship-to-shore data communications, (4) advancing quality evaluation of observations, and (5) developing a unified data management approach for observations and metadata that meets the needs of a diverse user community. Recommendations are made focusing on integrating private and autonomous vessels into the observing system, investing in sensor and communications technology development, developing an integrated data management structure that includes all types of ships, and moving towards a quality evaluation process that will result in a subset of ships being defined as mobile reference ships that will support climate studies. We envision a future where commercial, research, and privately-owned vessels are making multivariate observations using a combination of automated and human-observed measurements. All data and metadata will be documented, tracked, evaluated, distributed, and archived to benefit users of marine data. This vision looks at ships as a holistic network, not a set of disparate commercial, research, and/or third-party activities working in isolation, to bring these communities together for the mutual benefit of all.

BACKGROUND: Leptomeningeal spread in non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations who experience disease progression on TKIs portends a poor prognosis. Mutation profiling of tumour DNA in cerebrospinal fluid (CSF) samples can be used to determine the presence of the EGFR T790M resistance mutation, indicating that osimertinib, a CNS-penetrating 3(rd) generation TKI may be efficacious. METHODS: Eight patients on EGFR TKIs who progressed with cytology-proven leptomeningeal disease at our institution were studied. EGFR mutations were profiled in CSF using droplet digital PCR (ddPCR) and compared to matched plasma samples. Clinical characteristics and survival outcomes on subsequent therapies tailored to ddPCR analysis were reported. RESULTS: None of the four patients who developed leptomeningeal disease while receiving 1st generation EGFR TKIs developed the EGFR T790M mutation in CSF. One patient who did not have extra-cranial disease and was EGFR T790M-negative in both plasma and CSF was nevertheless treated with standard-dose osimertinib, and achieved a rapid and durable response lasting 9 months to date. Three patients developed leptomeningeal disease on osimertinib, with one patient developing the EGFR C797S mutation in a cis-allelic conformation with the EGFR T790M mutation in plasma. CONCLUSIONS: Standard-dose osimertinib resulted in a clinically meaningful response in a patient with EGFR T790M-negative 1st generation EGFR TKI refractory leptomeningeal disease. Next generation sequencing and ddPCR has a role at identifying the C797S mutation and its allelic conformation with the T790M mutation with clinical implications.

Volatile organic compounds (VOCs) are important precursors to the formation of ozone and fine particulate matter, the two pollutants of most concern in Sydney, Australia. Despite this importance, there are very few published measurements of ambient VOC concentrations in Australia. In this paper, we present mole fractions of several important VOCs measured during the campaign known as MUMBA (Measurements of Urban, Marine and Biogenic Air) in the Australian city of Wollongong (34&deg, S). We particularly focus on measurements made during periods when clean marine air impacted the measurement site and on VOCs of biogenic origin. Typical unpolluted marine air mole fractions during austral summer 2012-2013 at latitude 34&deg, S were established for CO2 (391.0 &plusmn, 0.6 ppm), CH4 (1760.1 &plusmn, 0.4 ppb), N2O (325.04 &plusmn, 0.08 ppb), CO (52.4 &plusmn, 1.7 ppb), O3 (20.5 &plusmn, 1.1 ppb), acetaldehyde (190 &plusmn, 40 ppt), acetone (260 &plusmn, 30 ppt), dimethyl sulphide (50 &plusmn, 10 ppt), benzene (20 &plusmn, 10 ppt), toluene (30 &plusmn, 20 ppt), C8H10 aromatics (23 &plusmn, 6 ppt) and C9H12 aromatics (36 &plusmn, 7 ppt). The MUMBA site was frequently influenced by VOCs of biogenic origin from a nearby strip of forested parkland to the east due to the dominant north-easterly afternoon sea breeze. VOCs from the more distant densely forested escarpment to the west also impacted the site, especially during two days of extreme heat and strong westerly winds. The relative amounts of different biogenic VOCs observed for these two biomes differed, with much larger increases of isoprene than of monoterpenes or methanol during the hot westerly winds from the escarpment than with cooler winds from the east. However, whether this was due to different vegetation types or was solely the result of the extreme temperatures is not entirely clear. We conclude that the clean marine air and biogenic signatures measured during the MUMBA campaign provide useful information about the typical abundance of several key VOCs and can be used to constrain chemical transport model simulations of the atmosphere in this poorly sampled region of the world.

Introduction: The cancer research community increasingly question the rigidity of eligibility criteria in clinical trials. Common reasons for “screen failure” (RFSF) are well documented; however, their effect on subsequent standard therapy (SST) and outcomes is unclear. Methods: This retrospective study evaluated patients aged ≥18 years with solid malignancy who were listed as ineligible on a screening log between February 2011 and March 2018. Patients screen-failed for biomarker results or incorrect cancer stage/prior treatment profile were excluded. Data were collected from electronic hospital records, including demographics, cancer history, RFSF, subsequent therapy, and outcomes. Results: Overall, 217 patients were eligible. The most common histologies were lung (28%), melanoma, colon, and pancreatic (all 11%); 90% were metastatic. The most common RFSF were rapid disease progression (PD; 16%), performance status (PS) ≥2 (12%), and abnormal liver function tests (aLFT; 12%). After screen failure, 129/217 (59%) had SST; 9 were dose-reduced. Treatment-naïve or phase III trial-ineligible patients were more likely to receive SST than those pre-treated or phase I trial-ineligible (72/104 vs. 52/113, p = 0.0006; 71/109 vs. 15/42, p = 0.00013), respectively. RFSF stabilised/improved in 104/217 (48%); the main RFSF was co-morbidity (19/104). The most common RFSF to deteriorate were rapid PD (27/72), PS ≥2 (20/72), and aLFT with liver metastases (LM; 13/72). Conclusions: RFSF related to organ function rarely deteriorate unless directly involved with underlying malignancy. Most RFSF do not prevent patients from having SST, nor increase dose reductions, especially in treatment-naïve/phase III trial-ineligible patients. Those with RFSF of poor PS, rapid PD, and aLFT from LM are less suitable for SST. Careful broadening of trial eligibility is warranted.

Aedes aegypti and Anopheles gambiae harbor the causative agents of diseases such as dengue fever and malaria, afflicting human morbidity and mortality worldwide. Given the worldwide emergence of resistance to insecticides, the current mainstay for vector control, identification of alternative modes of action for future insecticides is paramount. The serotonergic (5-HT) system has been documented to impact physiological mechanisms involved in disease transmission, suggesting its potential as a new mode of action target for future insecticide development. Target 5-HT receptors were cloned and expressed in the HEK293 cell line for functional and pharmacological characterization. Manipulation of the 5-HT system through microinjection of compounds suggests its involvement in the modulation of flight performance and blood-feeding behavior. By attenuating these two determinants of vectorial capacity, transmission and burden of disease could effectively be reduced. Considering these positive global health implications, the 5-HT system is a compelling target for the novel insecticide pipeline.

A likely important feature of the poorly understood aerosol‐cloud interactions over the Southern Ocean (SO) is the dominant role of sea spray aerosol, versus terrestrial aerosol. Ice nucleating particles (INPs), or particles required for heterogeneous ice nucleation, present over the SO have not been studied in several decades. In this study, boundary layer aerosol properties and immersion freezing INP number concentrations (nINPs) were measured during a ship campaign that occurred south of Australia (down to 53 °S) in March‐April 2016. Ocean surface chlorophyll‐a concentrations ranged from 0.11‐1.77 mg m‐3 and nINPs were a factor of 100 lower than historical surveys, ranging from 0.38 to 4.6 m‐3 at ‐20 °C. The INP population included organic heat‐stable material, with contributions from heat‐labile material. Lower INP source potentials of SO seawater samples compared to Arctic seawater were consistent with lower ice nucleating site densities in this study compared to north Atlantic air masses.

Ship-based measurements are an important component in developing an understanding of the global atmosphere. A common problem that impacts the quality of atmospheric data collected from marine research vessels is exhaust from both diesel combustion and waste incineration from the ship itself. Described here is an algorithm, developed for the recently commissioned Australian blue-water Research Vessel (RV) Investigator, that identifies exhaust periods in sampled air. The RV Investigator, with two dedicated atmospheric laboratories, represents an unprecedented opportunity for high quality measurements of the marine atmosphere. The algorithm avoids using ancillary data such as wind speed and direction, and instead utilises components of the exhaust itself – aerosol number concentration, black carbon concentration, and carbon monoxide and carbon dioxide mixing ratios. The exhaust signal is identified within each of these parameters individually before they are combined and an additional window filter is applied. The algorithm relies heavily on statistical methods, rather than setting thresholds that are too rigid to accommodate potential temporal changes. The algorithm is more effective than traditional wind-based filters in removing exhaust data without removing exhaust-free data which commonly occurs with traditional filters. With suitable testing, the algorithm has the potential to be applied to other ship-based atmospheric measurements where suitable measurements exist.

We present the organization, instrumentation, datasets, data interpretation, modeling, and accomplishments of the multinational global atmospheric measurement program AGAGE (Advanced Global Atmospheric Gases Experiment). AGAGE is distinguished by its capability to measure globally, at high frequency, and at multiple sites all the important species in the Montreal Protocol and all the important non-carbon-dioxide (non-CO[subscript 2]) gases assessed by the Intergovernmental Panel on Climate Change (CO[subscript 2] is also measured at several sites). The scientific objectives of AGAGE are important in furthering our understanding of global chemical and climatic phenomena. They are the following: (1) to accurately measure the temporal and spatial distributions of anthropogenic gases that contribute the majority of reactive halogen to the stratosphere and/or are strong infrared absorbers (chlorocarbons, chlorofluorocarbons – CFCs, bromocarbons, hydrochlorofluorocarbons – HCFCs, hydrofluorocarbons – HFCs and polyfluorinated compounds (perfluorocarbons – PFCs), nitrogen trifluoride – NF[subscript 3], sulfuryl fluoride – SO[subscript 2]F[subscript 2], and sulfur hexafluoride – SF[subscript 6]) and use these measurements to determine the global rates of their emission and/or destruction (i.e., lifetimes); (2) to accurately measure the global distributions and temporal behaviors and determine the sources and sinks of non-CO[subscript 2] biogenic–anthropogenic gases important to climate change and/or ozone depletion (methane – CH[subscript 4], nitrous oxide – N[subscript 2]O, carbon monoxide – CO, molecular hydrogen – H[subscript 2], methyl chloride – CH[subscript 3]Cl, and methyl bromide – CH[subscript 3]Br); (3) to identify new long-lived greenhouse and ozone-depleting gases (e.g., SO[subscript 2]F[subscript 2], NF[subscript 3], heavy PFCs (C[subscript 4]F[subscript 10], C[subscript 5]F[subscript 12], C[subscript 6]F[subscript 14], C[subscript 7]F[subscript 16], and C[subscript 8]F[subscript 18]) and hydrofluoroolefins (HFOs; e.g., CH[subscript 2] = CFCF[subscript 3]) have been identified in AGAGE), initiate the real-time monitoring of these new gases, and reconstruct their past histories from AGAGE, air archive, and firn air measurements; (4) to determine the average concentrations and trends of tropospheric hydroxyl radicals (OH) from the rates of destruction of atmospheric trichloroethane (CH[subscript 3]CCl[subscript 3]), HFCs, and HCFCs and estimates of their emissions; (5) to determine from atmospheric observations and estimates of their destruction rates the magnitudes and distributions by region of surface sources and sinks of all measured gases; (6) to provide accurate data on the global accumulation of many of these trace gases that are used to test the synoptic-, regional-, and global-scale circulations predicted by three-dimensional models; and (7) to provide global and regional measurements of methane, carbon monoxide, and molecular hydrogen and estimates of hydroxyl levels to test primary atmospheric oxidation pathways at midlatitudes and the tropics. Network Information and Data Repository: http://agage.mit.edu/data or http://cdiac.ess-dive.lbl.gov/ndps/alegage.html (https://doi.org/10.3334/CDIAC/atg.db1001)., United States. National Aeronautics and Space Administration (NAG5-12669), United States. National Aeronautics and Space Administration (NNX07AE89G), United States. National Aeronautics and Space Administration (NNX11AF17G), United States. National Aeronautics and Space Administration (NNX16AC98G)

We discuss remote terrestrial influences on boundary layer air over the Southern Ocean and Antarctica, and the mechanisms by which they arise, using atmospheric radon observations as a proxy. Our primary motivation was to enhance the scientific community’s ability to understand and quantify the potential effects of pollution, nutrient or pollen transport from distant land masses to these remote, sparsely instrumented regions. Seasonal radon characteristics are discussed at 6 stations (Macquarie Island, King Sejong, Neumayer, Dumont d’Urville, Jang Bogo and Dome Concordia) using 1–4 years of continuous observations. Context is provided for differences observed between these sites by Southern Ocean radon transects between 45 and 67°S made by the Research Vessel Investigator. Synoptic transport of continental air within the marine boundary layer (MBL) dominated radon seasonal cycles in the mid-Southern Ocean site (Macquarie Island). MBL synoptic transport, tropospheric injection, and Antarctic outflow all contributed to the seasonal cycle at the sub-Antarctic site (King Sejong). Tropospheric subsidence and injection events delivered terrestrially influenced air to the Southern Ocean MBL in the vicinity of the circumpolar trough (or “Polar Front”). Katabatic outflow events from Antarctica were observed to modify trace gas and aerosol characteristics of the MBL 100–200 km off the coast. Radon seasonal cycles at coastal Antarctic sites were dominated by a combination of local radon sources in summer and subsidence of terrestrially influenced tropospheric air, whereas those on the Antarctic Plateau were primarily controlled by tropospheric subsidence. Separate characterization of long-term marine and katabatic flow air masses at Dumont d’Urville revealed monthly mean differences in summer of up to 5 ppbv in ozone and 0.3 ng m-3 in gaseous elemental mercury. These differences were largely attributed to chemical processes on the Antarctic Plateau. A comparison of our observations with some Antarctic radon simulations by global climate models over the past two decades indicated that: (i) some models overestimate synoptic transport to Antarctica in the MBL, (ii) the seasonality of the Antarctic ice sheet needs to be better represented in models, (iii) coastal Antarctic radon sources need to be taken into account, and (iv) the underestimation of radon in subsiding tropospheric air needs to be investigated.

This study uses two climate models and six scenarios of prescribed methane emissions to compare modelled and observed atmospheric methane between 1994 and 2007, for Cape Grim, Australia (40.7° S, 144.7° E). The model simulations follow the TransCom-CH4 protocol and use the Australian Community Climate and Earth System Simulator (ACCESS) and the CSIRO Conformal-Cubic Atmospheric Model (CCAM). Radon is also simulated and used to reduce the impact of transport differences between the models and observations. Comparisons are made for air samples that have traversed the Australian continent. All six emission scenarios give modelled concentrations that are broadly consistent with those observed. There are three notable mismatches, however. Firstly, scenarios that incorporate interannually varying biomass burning emissions produce anomalously high methane concentrations at Cape Grim at times of large fire events in southeastern Australia, most likely due to the fire methane emissions being unrealistically input into the lowest model level. Secondly, scenarios with wetland methane emissions in the austral winter overestimate methane concentrations at Cape Grim during wintertime while scenarios without winter wetland emissions perform better. Finally, all scenarios fail to represent a~methane source in austral spring implied by the observations. It is possible that the timing of wetland emissions in the scenarios is incorrect with recent satellite measurements suggesting an austral spring (September–October–November), rather than winter, maximum for wetland emissions.

Routine chest X-ray (CXR) is recommended for neutropenic fever (NF) management however its role is relatively understudied in haematology patients.To investigate the utility of CXR in the diagnosis and management of patients with haematological conditions complicated by NF.Retrospective, single-centre analysis of haematology patients admitted with NF between January 2011 and December 2015. Baseline demographics, treatment details and outcomes were collected from electronic patient records. CXR underwent independent radiology review. Primary endpoints were a proportion of NF episodes in which CXR detected a probable chest infection in the absence of respiratory symptoms/signs and/or resulted in a change in antibiotic management.Four hundred and thirty-five episodes were identified; CXR was performed in 75% of patients (65% within 2 days of NF). In 4 of 164 (2.4%) asymptomatic patients, CXR was consistent with infection, in contrast to 19 of 119 (16%) patients with clinical signs of respiratory infection. Only 3 of 283 (1.1%) CXR resulted in a change to antibiotics. CXR consistent with infection was not associated with increased mortality or increased admission length, although there was an association with intensive care unit admission (odds ratios: 7.61, 95% confidence interval: 2.04-28.31).In haematology patients with NF, CXR rarely detected chest infection or changed management in patients with no respiratory symptoms or signs. CXR in our institution is no longer part of routine assessment of NF in the absence of these features.

e19027 Background: Pts with iNHL undergo active surveillance to detect disease relapse or progression. International guidelines recommend regular RBTs for surveillance but evidence for this practice is lacking. Methods: We conducted a retrospective analysis of pts aged ≥16 yrs from 2008-17 undergoing routine surveillance at 2 Australian centres for grade 1-3a follicular lymphoma (FL) or marginal zone lymphoma (MZL), to assess the utility of full blood count, lactate dehydrogenase & beta-2-microglobulin to detect progression events; (i.e relapse or progression) or to change management. Abnormal results were defined as acute deviations from local laboratory normal ranges not explained by a concurrent medical condition. Eligible pts were either treatment-naive or had achieved a response to lymphoma-directed therapy, had ≥6 mths follow up and an absence of progression events within 3 mths of prior therapy. Demographic data were collected as well as treatment, follow up appointment (appt) details including presence of signs/symptoms, RBT results, survival status & further therapy. The study was ethically approved. Results: 180 eligible pts (FL:142, MZL:38) underwent 1757 follow up appts (median follow up 38 months). RBTs were done at 83% of appts. 74 progression events occurred in a total of 62 pts; 48/74 (65%) had immediate therapy. 2/74 (3%) were detected by RBTs alone, (both treatment naïve pts); 88% by signs/symptoms & 9% by routine imaging. 20/243 (8%) of abnormal RBTs in asymptomatic pts led to a change in subsequent management (10 had imaging; 8 earlier appts; 2 repeat RBTs alone). The sensitivity & positive predictive value of abnormal RBTs to detect progression events were 39% & 9% respectively. In asymptomatic patients, the number of RBTs required to change management and to detect a progression event were 64 and 644 respectively. Conclusions: RBTs rarely detect clinically significant disease progression or relapse and seldom solely lead to a change in management in asymptomatic pts with iNHL. Clinical signs/symptoms are far more likely to detect progression or relapse. Guidelines should reflect the benefit & risk of RBTs in the clinical setting.

A chemistry-transport model (CTM) intercomparison experiment (TransCom-CH4) has been designed to investigate the roles of surface emissions, transport and chemical loss in simulating the global methane distribution. Model simulations were conducted using twelve models and four model variants and results were archived for the period of 1990–2007. All but one model transports were driven by reanalysis products from 3 different meteorological agencies. The transport and removal of CH4 in six different emission scenarios were simulated, with net global emissions of 513 ± 9 and 514 ± 14 Tg CH4 yr−1 for the 1990s and 2000s, respectively. Additionally, sulfur hexafluoride (SF6) was simulated to check the interhemispheric transport, radon (222Rn) to check the subgrid scale transport, and methyl chloroform (CH3CCl3) to check the chemical removal by the tropospheric hydroxyl radical (OH). The results are compared to monthly or annual mean time series of CH4, SF6 and CH3CCl3 measurements from 8 selected background sites, and to satellite observations of CH4 in the upper troposphere and stratosphere. Most models adequately capture the vertical gradients in the stratosphere, the average long-term trends, seasonal cycles, interannual variations (IAVs) and interhemispheric (IH) gradients at the surface sites for SF6, CH3CCl3 and CH4. The vertical gradients of all tracers between the surface and the upper troposphere are consistent within the models, revealing vertical transport differences between models. An average IH exchange time of 1.39 ± 0.18 yr is derived from SF6 time series. Sensitivity simulations suggest that the estimated trends in exchange time, over the period of 1996–2007, are caused by a change of SF6 emissions towards the tropics. Using six sets of emission scenarios, we show that the decadal average CH4 growth rate likely reached equilibrium in the early 2000s due to the flattening of anthropogenic emission growth since the late 1990s. Up to 60% of the IAVs in the observed CH4 concentrations can be explained by accounting for the IAVs in emissions, from biomass burning and wetlands, as well as meteorology in the forward models. The modeled CH4 budget is shown to depend strongly on the troposphere-stratosphere exchange rate and thus on the model's vertical grid structure and circulation in the lower stratosphere. The 15-model median CH4 and CH3CCl3 atmospheric lifetimes are estimated to be 9.99 ± 0.08 and 4.61 ± 0.13 yr, respectively, with little IAV due to transport and temperature.

We assess the performance of an inverse Lagrangian dispersion technique for its suitability to quantify leakages from geological storage of CO2. We find the technique is accurate ( 〈 Q bLS / Q 〉 = 0.99 , σ = 0.29 ) when strict meteorological filtering is applied to ensure that Monin–Obukhov Similarity Theory is valid for the periods analysed and when downwind enrichments in tracer gas concentration are 1% or more above background concentration. Because of their respective baseline atmospheric concentrations, this enrichment criterion is less onerous for CH4 than for CO2. Therefore for geologically sequestered gas reservoirs with a significant CH4 component, monitoring CH4 as a surrogate for CO2 leakage could be as much as 10 times more sensitive than monitoring CO2 alone. Additional recommendations for designing a robust atmospheric monitoring strategy for geosequestration include: continuous concentration data; exact inter-calibration of up- and downwind concentration measurements; use of an array of point concentration sensors to maximise the use of spatial information about the leakage plume; and precise isotope ratio measurement to confirm the source of any concentration elevations detected.

Infrared spectra of mass-selected F - -(CH 4 ) n (n = 1-8) clusters are recorded in the CH stretching region (2500-3100 cm -1 ). Spectra for the n = 1-3 clusters are interpreted with the aid of ab initio calculations at the MP2/6-311++G(2df 2p) level, which suggest that the CH4 ligands bind to F - by equivalent, linear hydrogen bonds. Anharmonic frequencies for CH 4 and F - -CH 4 are determined using the vibrational self-consistent field method with second-order perturbation theory correction. The n = 1 complex is predicted to have a C 3v structure with a single CH group hydrogen bonded to F - . Its spectrum exhibits a parallel band associated with a stretching vibration of the hydrogen-bonded CH group that is red-shifted by 380 cm -1 from the v 1 band of free CH 4 and a perpendicular band associated with the asymmetric stretching motion of the nonbonded CH groups, slightly red-shifted from the v 3 band of free CH 4 . As n increases, additional vibrational bands appear as a result of Fermi resonances between the hydrogen-bonded CH stretching vibrational mode and the 2v 4 overtone and v 2 + v 4 combination levels of the methane solvent molecules. For clusters with n ≤ 8, it appears that the CH 4 molecules are accommodated in the first solvation shell, each being attached to the F - anion by equivalent hydrogen bonds.

The infrared spectrum of F−–H2 is measured over the H–H stretch region. The νHH transition occurs at 3220 cm−1, displaced 940 cm−1 to lower energy from the H2 fundamental vibrational transition. A weaker band at 3640 cm−1 is assigned to νHH in combination with the intermolecular stretch vibration (νHH + νs). The experimental νHH frequency agrees with a prediction based on an ab initio H–H potential energy curve calculated at the CCSD(T)/aug-cc-pVQZ level. Absence of resolved rotational structure in the νHH band suggests that rovibrational lines are lifetime broadened and that F−–H2 in the νHH = 1 level predissociates on a < 3 ps timescale.

Infrared spectra of Cl − –C 2 H 2 ·Ar, Br − –C 2 H 2 ·Ar, and I − –C 2 H 2 ·Ar are recorded in the C–H stretch region by monitoring production of X − –C 2 H 2 photofragments. Each spectrum exhibits a single band corresponding to the vibration of a hydrogen-bonded C–H unit ( ν HB =2882, 2982, 3075 cm −1 for Cl − –C 2 H 2 ·Ar, Br − –C 2 H 2 ·Ar, I − –C 2 H 2 ·Ar, respectively). Marked differences between the spectra of Cl − –C 2 H 2 ·Ar and Cl − –C 2 H 2 are attributable to the strong Cl − –HCCH bond which prevents cold Cl − –C 2 H 2 complexes from dissociating following absorption of an infrared photon. The evidence suggests that addition of the first few Ar solvent atoms has a minor influence on the C–H stretch vibrations of the halide–acetylene complexes.

Infrared spectra are obtained for the F − –CH 4 and Br − –CH 4 anion complexes in the region of the C–H stretch vibrations of the CH 4 sub-unit. Spectra of both species exhibit two bands in the 2500–3000 cm −1 range. One band, a perpendicular transition distinguished by characteristic Q branches, is slightly red shifted from the ν 3 ( t 2 ) band of CH 4 (Δ ν =−68 cm −1 for F − –CH 4 and −34 cm −1 for Br − –CH 4 ). The other band, a parallel transition, corresponding mainly to vibrational motion of the hydrogen-bonded proton, is red shifted from the ν 1 ( a 1 ) transition of CH 4 (Δ ν =−380 cm −1 for F − –CH 4 , and −31 cm −1 for Br − –CH 4 ). The spectra are compatible with C 3 v structures for the F − –CH 4 and Br − –CH 4 dimers, whereby the halide anions are hydrogen-bonded to the CH 4 molecule through a single C–H unit.

Infrared vibrational predissociation spectra are reported for size-selected F-−(D2)n (n = 1−6) and Cl-−(D2)n (n = 1−3) clusters in the D−D stretch region. The F-−(D2)n and Cl-−(D2)n spectra each feature a single band shifted to lower energy from the bare D2 stretching frequency that moves to higher frequency with increasing cluster size. Vibrational band shifts are substantially larger for F-−(D2)n than for Cl-−(D2)n, reflecting the stronger F-- - -D2 interaction. The spectra are compatible with the F-−(D2)n and Cl-−(D2)n clusters containing roughly equivalent D2 ligands that are attached end-on to a central halide anion core. The unobserved D−D stretch band of the F-−D2 complex is predicted to lie at ∼2400 cm-1.

At any one time, close to 700,000 beef cattle are raised intensively in Australian feedlots. This chapter describes measurements of emissions of the greenhouse gas N2O and the reactive nitrogen gases NH3 and NOx from two Australian beef cattle feedlots made over two years with open- and closed-path concentration measurement systems and backward Lagrangian stochastic dispersion modelling. Emissions of all three gases exhibited marked diurnal cycles with maxima close to mid-day and minima over night. The average emission rate for N2O was 1.3 ± 1.65 (s.d) kg N ha−1 d−1, that for NH3 was 95 ± 36 kg N ha−1 d−1, and for NOx 1.20 ± 0.58 kg N ha−1 d−1. Extrapolating these figures to all the feedlots in the country and accepting the estimate by Mosier et al. (1998) that 1 % of the NH3 and NOx would be converted to N2O after eventual deposition, the direct emissions of N2O from feedlots amount to 241 kt CO2-e year−1 and those from NH3 plus NOx to 181 kt CO2-e year−1, or 43 % of the total N2O emissions. These direct and indirect emissions are substantial, amounting to 60 % in terms of CO2-e of the CH4 emissions measured in the project.

Background Patients with HGL achieving complete remission (CR) after first-line combination chemotherapy undergo regular surveillance to detect early signs of relapse. As follow-up imaging is associated with increased radiation-related risk and minimal benefit in asymptomatic (aSx) patients, imaging as surveillance is no longer routine. (Eichenauer Ann Oncol 2014, Tilly Ann Oncol 2015) Regular laboratory testing (Labs) still feature in internationally-recognised surveillance guidelines (eg NCCN), despite limited evidence in the modern era for their use in relapse detection. Studies conducted prior to modern imaging (PET/CT) and use of rituximab suggested LDH and ESR may be useful, and more recently the absolute lymphocyte count (ALC) and lymphocyte-monocyte ratio (LMR) have shown promise in small series (Weeks JCO 1991, Henry-Amar Ann Int Med 1991,Wei Leuk Lymph 2015, Porrata Leukemia 2010). However large scale data are lacking hence there is no consensus on the value and optimum frequency of specific laboratory parameters for use in routine surveillance of HGL. Methods We conducted a retrospective analysis of patients with histologically-proven cHL, DLBCL, T-cell lymphoma or Burkitt lymphoma receiving curative-intent treatment over a 15-year period. Eligible patients were aged≥16years, in CR for ≥3 months & had >12months follow-up. Primary CNS lymphoma, HIV-associated lymphomas and transformation from indolent subtypes were excluded. Data were collated from patient records. Laboratory results were considered abnormal if a) FBE, ALC, neutrophil count, absolute monocyte count (AMC), ESR or LDH fell outside local laboratory normal limits b) the derangement was not present previously and c) could not be explained by a concurrent medical condition. Abnormal Lab results were investigated at clinician discretion. Labs were evaluated based on their independent ability to detect relapse within 3 months of confirmation. Kaplan-Meier method was used for survival analysis and compared by the log-rank test between groups. Results Between 2000-2015, 346 eligible patients underwent 3048 outpatient visits. Median follow-up was 30 months (range 3-184). Labs were performed at 90% of appointments: FBE in 99.7%, LDH in 78% (of NHL), ESR in 38% (of HL) with abnormalities in 26%, 12% and 16% respectively. Fifty-five patients relapsed (16%). Routine Labs detected aSx relapse in 3/55 (5%); routine imaging detected 9/55 relapses (16%) and clinical symptoms/signs lead to diagnosis of relapse in 43/55 (78%; 19/43 were unscheduled visits). Unscheduled appointments due to patient-reported symptoms (3% of all visits) showed a significantly stronger association with relapse than scheduled visits (OR 50.4, p Table 1 presents sensitivity, specificity, PPV and NPV of Labs, demonstrating in particular a low PPV and high NPV. ALC, AMC and LMR were very poor markers for relapse, with area under the curve of 0.517, 0.529 and 0.576 respectively. In addition, an abnormal Lab result prompted a change in management for only 16% of aSx patients, (37 imaging, 38 repeat Labs, 22 earlier scheduling of next review), compared to 59% with symptoms/signs. In 43 episodes, abnormal Labs lead to further investigations which were subsequently negative (25 imaging, 6 biopsies, 11 repeat Labs). There was no significant difference in OS between patients who had Labs performed ≥3 months prior to documented relapse versus patients who did not (p=0.88, figure 1). Conclusion Although normal Lab results have a high NPV for relapse, most HGL relapses are detected by patient-reported symptoms, often at unscheduled visits. Abnormal Labs in aSx patients infrequently trigger a change in management. Routine Labs rarely detect relapse in aSx patients with HGL in CR after primary curative-intent chemotherapy, demonstrate unacceptably poor performance characteristics, have no impact on survival and have limited value in routine surveillance. Disclosures Hawkes: BMS: Other: travel expenses, Research Funding; Takeda: Other: travel expenses; Merck Serono: Research Funding.