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Purpose: The service configuration with distinct child and adolescent mental health services (CAMHS) and adult mental health services (AMHS) may be a barrier to continuity of care. Because of a lack of transition policy, CAMHS clinicians have to decide whether and when a young person should transition to AMHS. This study describes which characteristics are associated with the clinicians’ advice to continue treatment at AMHS. Methods: Demographic, family, clinical, treatment, and service-use characteristics of the MILESTONE cohort of 763 young people from 39 CAMHS in Europe were assessed using multi-informant and standardized assessment tools. Logistic mixed models were fitted to assess the relationship between these characteristics and clinicians’ transition recommendations. Results: Young people with higher clinician-rated severity of psychopathology scores, with self- and parent-reported need for ongoing treatment, with lower everyday functional skills and without self-reported psychotic experiences were more likely to be recommended to continue treatment. Among those who had been recommended to continue treatment, young people who used psychotropic medication, who had been in CAMHS for more than a year, and for whom appropriate AMHS were available were more likely to be recommended to continue treatment at AMHS. Young people whose parents indicated a need for ongoing treatment were more likely to be recommended to stay in CAMHS. Conclusion: Although the decision regarding continuity of treatment was mostly determined by a small set of clinical characteristics, the recommendation to continue treatment at AMHS was mostly affected by service-use related characteristics, such as the availability of appropriate services.

BACKGROUND: The Combination Antibiotic Therapy for Methicillin-Resistant Staphylococcus aureus (CAMERA2) trial ceased recruitment in July 2018, noting that a higher proportion of patients in the intervention arm (combination therapy) developed acute kidney injury (AKI) compared to the standard therapy (monotherapy) arm. We analyzed the long-term outcomes of participants in CAMERA2 to understand the impact of combination antibiotic therapy and AKI. METHODS: Trial sites obtained additional follow-up data. The primary outcome was all-cause mortality, censored at death or the date of last known follow-up. Secondary outcomes included kidney failure or a reduction in kidney function (a 40% reduction in estimated glomerular filtration rate to <60 mL/minute/1.73 m2). To determine independent predictors of mortality in this cohort, adjusted hazard ratios were calculated using a Cox proportional hazards regression model. RESULTS: This post hoc analysis included extended follow-up data for 260 patients. Overall, 123 of 260 (47%) of participants died, with a median population survival estimate of 3.4 years (235 deaths per 1000 person-years). Fifty-five patients died within 90 days after CAMERA2 trial randomization; another 68 deaths occurred after day 90. Using univariable Cox proportional hazards regression, mortality was not associated with either the assigned treatment arm in CAMERA2 (hazard ratio [HR], 0.84 [95% confidence interval [CI], .59-1.19]; P = .33) or experiencing an AKI (HR at 1 year, 1.04 [95% CI, .64-1.68]; P = .88). CONCLUSIONS: In this cohort of patients hospitalized with methicillin-resistant S aureus bacteremia, we found no association between either treatment arm of the CAMERA2 trial or AKI (using CAMERA2 trial definition) and longer-term mortality.

Contains fulltext : 300092.pdf (Publisher’s version ) (Open Access), BACKGROUND: To date, azoles represent the only viable option for oral treatment of invasive Candida infections, while rates of azole resistance among non-albicans Candida spp. continue to increase. The objective of this sub-analysis of the European multicenter observational cohort study Candida III was to describe demographical and clinical characteristics of the cohort requiring prolonged hospitalization solely to complete intravenous (iv) antifungal treatment (AF Tx). METHODS: Each participating hospital (number of eligible hospitals per country determined by population size) included the first ~ 10 blood culture proven adult candidemia cases occurring consecutively after July 1st, 2018, and treating physicians answered the question on whether hospital stay was prolonged only for completion of intravenous antifungal therapy. Descriptive analyses as well as binary logistic regression was used to assess for predictors of prolonged hospitalization solely to complete iv AF Tx. FINDINGS: Hospital stay was prolonged solely for the completion of iv AF Tx in 16% (100/621) of candidemia cases by a median of 16 days (IQR 8 - 28). In the multivariable model, initial echinocandin treatment was a positive predictor for prolonged hospitalization to complete iv AF Tx (aOR 2.87, 95% CI 1.55 - 5.32, p < 0.001), while (i) neutropenia, (ii) intensive care unit admission, (iii) catheter related candidemia, (iv) total parenteral nutrition, and (v) C. parapsilosis as causative pathogen were found to be negative predictors (aOR 0.22 - 0.45; p < 0.03). INTERPRETATION: Hospital stays were prolonged due to need of iv AF Tx in 16% of patients with candidemia. Those patients were more likely to receive echinocandins as initial treatment and were less severely ill and less likely infected with C. parapsilosis., 01 december 2023

Item does not contain fulltext, BACKGROUND: The European Confederation of Medical Mycology (ECMM) collected data on epidemiology, risk factors, treatment, and outcomes of patients with culture-proven candidaemia across Europe to assess how adherence to guideline recommendations is associated with outcomes. METHODS: In this observational cohort study, 64 participating hospitals located in 20 European countries, with the number of eligible hospitals per country determined by population size, included the first ten consecutive adults with culture-proven candidaemia after July 1, 2018, and entered data into the ECMM Candida Registry (FungiScope CandiReg). We assessed ECMM Quality of Clinical Candidaemia Management (EQUAL Candida) scores reflecting adherence to recommendations of the European Society of Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of America guidelines. FINDINGS: 632 patients with candidaemia were included from 64 institutions. Overall 90-day mortality was 43% (265/617), and increasing age, intensive care unit admission, point increases in the Charlson comorbidity index score, and Candida tropicalis as causative pathogen were independent baseline predictors of mortality in Cox regression analysis. EQUAL Candida score remained an independent predictor of mortality in the multivariable Cox regression analyses after adjusting for the baseline predictors, even after restricting the analysis to patients who survived for more than 7 days after diagnosis (adjusted hazard ratio 1·08 [95% CI 1·04-1·11; p<0·0001] in patients with a central venous catheter and 1·09 [1·05-1·13; p<0·0001] in those without one, per one score point decrease). Median duration of hospital stay was 15 days (IQR 4-30) after diagnosis of candidaemia and was extended specifically for completion of parenteral therapy in 100 (16%) of 621 patients. Initial echinocandin treatment was associated with lower overall mortality and longer duration of hospital stay among survivors than treatment

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Staphylococcus aureus bloodstream (SAB) infection is a common and severe infectious disease, with a 90-day mortality of 15%–30%. Despite this, <3000 people have been randomized into clinical trials of treatments for SAB infection. The limited evidence base partly results from clinical trials for SAB infections being difficult to complete at scale using traditional clinical trial methods. Here we provide the rationale and framework for an adaptive platform trial applied to SAB infections. We detail the design features of the Staphylococcus aureus Network Adaptive Platform (SNAP) trial that will enable multiple questions to be answered as efficiently as possible. The SNAP trial commenced enrolling patients across multiple countries in 2022 with an estimated target sample size of 7000 participants. This approach may serve as an exemplar to increase efficiency of clinical trials for other infectious disease syndromes.

BACKGROUND: Acute-on-chronic liver failure (ACLF) represents a rising global healthcare burden, characterised by increasing prevalence among patients with decompensated cirrhosis who have a 28-day transplantation-free mortality of 33.9%. Due to disease complexity and a high prevalence of socio-economic disadvantage, there are deficits in quality of care and adherence to guideline-based treatment in this cohort. Compared to other chronic conditions such as heart failure, those with liver disease have reduced access to integrated ambulatory care services. The LivR Well programme is a multidisciplinary intervention aimed at improving 28-day mortality and reducing 30-day readmission through a home-based, liver optimisation programme implemented in the first 28 days after an admission with either ACLF or hepatic decompensation. Outcomes from our feasibility study suggest that the intervention is safe and acceptable to patients and carers. METHODS: We will recruit adult patients with chronic liver disease from the emergency departments, in-patient admissions, and an ambulatory liver clinic of a multi-site quaternary health service in Melbourne, Australia. A total of 120 patients meeting EF-Clif criteria will be recruited to the ACLF arm, and 320 patients to the hepatic decompensation arm. Participants in each cohort will be randomised to the intervention arm, a 28-day multidisciplinary programme or to standard ambulatory care in a 1:1 ratio. The intervention arm includes access to nursing, pharmacy, physiotherapy, dietetics, social work, and neuropsychiatry clinicians. For the ACLF cohort, the primary outcome is 28-day mortality. For the hepatic decompensation cohort, the primary outcome is 30-day re-admission. Secondary outcomes assess changes in liver disease severity and quality of life. An interim analysis will be performed at 50% recruitment to consider early cessation of the trial if the intervention is superior to the control, as suggested in our feasibility study.

Past efforts to synthesize and quantify the magnitude and change in carbon dioxide (CO₂) fluxes in terrestrial ecosystems across the rapidly warming Arctic–boreal zone (ABZ) have provided valuable information but were limited in their geographical and temporal coverage. Furthermore, these efforts have been based on data aggregated over varying time periods, often with only minimal site ancillary data, thus limiting their potential to be used in large-scale carbon budget assessments. To bridge these gaps, we developed a standardized monthly database of Arctic–boreal CO₂ fluxes (ABCflux) that aggregates in situ measurements of terrestrial net ecosystem CO₂ exchange and its derived partitioned component fluxes: gross primary productivity and ecosystem respiration. The data span from 1989 to 2020 with over 70 supporting variables that describe key site conditions (e.g., vegetation and disturbance type), micrometeorological and environmental measurements (e.g., air and soil temperatures), and flux measurement techniques. Here, we describe these variables, the spatial and temporal distribution of observations, the main strengths and limitations of the database, and the potential research opportunities it enables. In total, ABCflux includes 244 sites and 6309 monthly observations; 136 sites and 2217 monthly observations represent tundra, and 108 sites and 4092 observations represent the boreal biome. The database includes fluxes estimated with chamber (19 % of the monthly observations), snow diffusion (3 %) and eddy covariance (78 %) techniques. The largest number of observations were collected during the climatological summer (June–August; 32 %), and fewer observations were available for autumn (September–October; 25 %), winter (December–February; 18 %), and spring (March–May; 25 %). ABCflux can be used in a wide array of empirical, remote sensing and modeling studies to improve understanding of the regional and temporal variability in CO₂ fluxes and to better es

The rate of invasive fungal infection (IFI) in patients with myelodysplasia (MDS) and acute myeloid leukaemia (AML) receiving 5-azacytidine is incompletely defined and published recommendations for mold-active fungal prophylaxis in such patients vary according to source. We performed a retrospective cohort study in order to identify contemporary IFI rates and infection-related mortality in relation to known risk factors and the use of anti-fungal prophylaxis. One-hundred seventeen patients receiving 5-azacytidine for MDS and low blast count AML were identified, of whom 71 (61%) received antifungal prophylaxis. The IFI rate was 7.7% across the entire cohort: 5.6% in those receiving prophylaxis vs. 10.9% in the subgroup who did not (p=0.30). The presence of neutropenia at three months of treatment was associated with increased IFI risk (hazard ratio [HR] 8.29; (95% confidence interval [CI)] 1.61-42.6; p=0.01) and on multivariate analysis, IFI was independently associated with increased all-cause mortality risk (HR 8.37; 95% CI 3.67 - 19.11; p<0.0001). These data further highlight the risk of IFI in this population and support the use of mold-active prophylaxis in neutropenic patients receiving 5-azacytidine for MDS and AML.Copyright This article is protected by copyright. All rights reserved.

BACKGROUND: The COVID-19 pandemic has generated significant debate about how emerging infections can be treated in the absence of evidence-based therapies to combat disease. In particular, the use of off-label therapies outside of a clinical trial setting has been controversial. AIM: We aimed to longitudinally study policies and prescribing practices pertaining to therapies for COVID-19 in Australian Health Services in 2020. METHOD(S): Prospective data was collected from participating Australian health services who may care for patients with COVID-19 via an electronic portal. A single informant from each health service was emailed a survey link at regular intervals. Information was sought regarding changes to COVID-19 policy at their service and use of therapies for COVID-19. RESULT(S): Overall, 78 hospitals were represented from 39 respondents with longitudinal data collection from May to December 2020. All Australian states/territories were represented with the majority of respondents located in a major city (34/39; 87%). Just over half (20/39) of respondents had a written policy for COVID-19 therapy use at their health service at survey enrolment and policies changed frequently throughout the pandemic. Therapy use outside of a clinical trial was reported in 54% of health services, most frequently in Victoria, correlating with higher numbers of COVID-19 cases. At study commencement hydroxychloroquine was most frequently used, with corticosteroids and remdesivir use increasingly throughout the study period. CONCLUSION(S): Our results reflect the reactive nature of prescribing of therapies for COVID-19 and highlight the importance of evidence-based guidelines to assist prescribers. This article is protected by copyright. All rights reserved.

The rate of invasive fungal infection (IFI) in patients with myelodysplasia (MDS) and acute myeloid leukemia (AML) receiving 5-azacytidine is incompletely defined and published recommendations for mold-active fungal prophylaxis in such patients vary according to source. We performed a retrospective cohort study in order to identify contemporary IFI rates and infection-related mortality in relation to known risk factors and the use of antifungal prophylaxis. One hundred and seventeen patients receiving 5-azacytidine for MDS and low blast count AML were identified, of whom 71 (61%) received antifungal prophylaxis. The IFI rate was 7.7% across the entire cohort: 5.6% in those receiving prophylaxis vs 10.9% in the subgroup who did not (P = .30). The presence of neutropenia at three months of treatment was associated with increased IFI risk (hazard ratio [HR] 8.29; (95% confidence interval [CI)] 1.61-42.6; P = .01), and on multivariate analysis, IFI was independently associated with increased all-cause mortality risk (HR 8.37; 95% CI 3.67 - 19.11; P < .0001). These data further highlight the risk of IFI in this population and support the use of mold-active prophylaxis in neutropenic patients receiving 5-azacytidine for MDS and AML.

Background: Convalescent plasma has been widely used to treat COVID-19 and is under investigation in numerous randomized clinical trials, but results are publicly available only for a small number of trials. The objective of this study was to assess the benefits of convalescent plasma treatment compared to placebo or no treatment and all-cause mortality in patients with COVID-19, using data from all available randomized clinical trials, including unpublished and ongoing trials (Open Science Framework, https://doi.org/10.17605/OSF.IO/GEHFX). Methods: In this collaborative systematic review and meta-analysis, clinical trial registries (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform), the Cochrane COVID-19 register, the LOVE database, and PubMed were searched until April 8, 2021. Investigators of trials registered by March 1, 2021, without published results were contacted via email. Eligible were ongoing, discontinued and completed randomized clinical trials that compared convalescent plasma with placebo or no treatment in COVID-19 patients, regardless of setting or treatment schedule. Aggregated mortality data were extracted from publications or provided by investigators of unpublished trials and combined using the Hartung–Knapp–Sidik–Jonkman random effects model. We investigated the contribution of unpublished trials to the overall evidence. Results: A total of 16,477 patients were included in 33 trials (20 unpublished with 3190 patients, 13 published with 13,287 patients). 32 trials enrolled only hospitalized patients (including 3 with only intensive care unit patients). Risk of bias was low for 29/33 trials. Of 8495 patients who received convalescent plasma, 1997 died (23%), and of 7982 control patients, 1952 died (24%). The combined risk ratio for all-cause mortality was 0.97 (95% confidence interval: 0.92; 1.02) with between-study heterogeneity not beyond chance (I2 = 0%). The RECOVERY trial had 69.8% and the unpublished evidence 25.3% of

Among patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia from a prospective randomized clinical trial, acute kidney injury (AKI) rates increased with increasing vancomycin exposure, even within the therapeutic range. AKI was independently more common for the (flu)cloxacillin group. Day 2 vancomycin AUC ≥470 mg·h/L was significantly associated with AKI, independent of (flu)cloxacillin receipt.

Objectives: To determine if lopinavir/ritonavir +/- hydroxychloroquine will reduce the proportion of participants who survive without requiring ventilatory support, 15 days after enrolment, in adult participants with non-critically ill SARS-CoV-2 infection. Trial design: ASCOT is an investigator-initiated, multi-centre, open-label, randomised controlled trial. Participants will have been hospitalised with confirmed COVID-19, and will be randomised 1:1:1:1 to receive lopinavir /ritonavir, hydroxychloroquine, both or neither drug in addition to standard of care management. Participants: Participants will be recruited from >80 hospitals across Australia and New Zealand, representing metropolitan and regional centres in both public and private sectors. Admitted patients will be eligible if aged ≥ 18 years, have confirmed SARS-CoV-2 by nucleic acid testing in the past 12 days and are expected to remain an inpatient for at least 48 hours from the time of randomisation. Potentially eligible participants will be excluded if admitted to intensive care or requiring high level respiratory support, are currently receiving study drugs or their use is contraindicated due to allergy, drug interaction or comorbidities (including baseline QTc prolongation of 470ms for women or 480ms for men), or death is anticipated imminently.

Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.

Background: Cefiderocol, ceftazidime-avibactam, ceftolozane-tazobactam, intravenous fosfomycin and plazomicin represent potential carbapenem sparing agents for extended-spectrum-beta-lactamase or AmpC beta-lactamase producing Escherichia coli infection. However, available data is limited in predicting the volume of carbapenem therapy which could be substituted and real-world contraindications. Method(s): We determined the number of carbapenem days of therapy (DOT) which could be substituted and frequent contraindications accounting for antimicrobial susceptibility and site of infection in an unselected cohort with ceftriaxone-non-susceptible E. coli bacteremia at a single health network from 2015 to 2016. Individual patient data was used to calculate DOT and substitution for each agent. Result(s): There were 108 episodes of E. coli bacteremia resulting in 67.2 carbapenem DOT/100 patient-days of antimicrobial therapy administered. Ceftazidime-avibactam could be used to substitute 36.2 DOT/100 patient-days (54%) for inpatient definitive therapy, ceftolozane-tazobactam for 34.7 DOT/100 patient-days (52%), cefiderocol for 27.1 DOT/100 patient-days (40%), fosfomycin for 23.3 DOT /100 patient-days (35%) and plazomicin for 27.1 DOT/100 patient-days (40%). Non-urinary tract source of infection was the most frequent contraindication to fosfomycin (25), plazomicin (26) and cefiderocol (26). Use in outpatient parenteral antimicrobial therapy (OPAT) programs accounted for 40% of DOT, all of which could be substituted if stability data allowed for ceftazidime-avibactam and ceftolozane-tazobactam. Conclusion(s): All tested agents could be used to replace a significant volume of carbapenem therapy. Establishing stability of these agents for use in OPAT is required for maximizing their use as carbapenem sparing agents while randomized clinical data is awaited for some of these agents in resistant E. coli bacteremia.Copyright © 2020, The Author(s).

Introduction Bloodstream infections are a leading cause of mortality and morbidity; the duration of treatment for these infections is understudied. Methods and analysis We will conduct an international, multicentre randomised clinical trial of shorter (7 days) versus longer (14 days) antibiotic treatment among hospitalised patients with bloodstream infections. The trial will include 3626 patients across 60 hospitals and 6 countries. We will include patients with blood cultures confirming a pathogenic bacterium after hospital admission. Exclusion criteria will include patient factors (severe immunosuppression), infection site factors (endocarditis, osteomyelitis, undrained abscesses, infected prosthetic material) and pathogen factors (Staphylococcus aureus, Staphylococcus lugdunensis, Candida and contaminant organisms). We will leave the selection of specific antibiotics, doses and route of delivery to the discretion of treating physicians; no placebo control will be used given the diversity of pathogens and sources of bacteraemia. The intervention will be assignment of treatment duration to be 7 versus 14 days. We will minimise selection bias via central randomisation with variable block sizes, with concealed allocation until day 7 of adequate antibiotic treatment. The primary outcome is 90-day survival; we will test whether 7 days is non-inferior to 14 days of treatment, with a non-inferiority margin of 4% absolute mortality. Secondary outcomes include hospital and intensive care unit (ICU) mortality, relapse rates of bacteraemia, hospital and ICU length of stay, mechanical ventilation and vasopressor duration, antibiotic-free days, Clostridium difficile infection, antibiotic allergy and adverse events and colonisation/infection with antibiotic-resistant organisms. Ethics and dissemination The study has been approved by the ethics review board at each participating site. Sunnybrook Health Sciences Centre is the central ethics committee. We will disseminate study re

This paper presents a novel interdisciplinary and catchment-based approach for exploring urban flood resilience. Our research identified and developed a diverse set of adaptation measures for Elwood, a suburb in Melbourne, Australia, that is vulnerable to pluvial and coastal flooding. We drew on methods from social science, urban design and environmental engineering to gain integrated insights into the opportunities for Elwood to increase its flood resilience and urban liveability. Results showed that an appropriate balance of social, infrastructural and urban design responses would be required to retreat from, accommodate and protect against flood risk. These would also deliver broader benefits such as securing water supplies through harvested stormwater and mitigating extreme heat through greener landscapes. Our interdisciplinary approach demonstrated the value of (i) engaging with the community to understand their concerns, aspirations and adaptation ideas, (ii) exploring design measures that densify and use urban forms in ways that implement adaptation measures while responding to local context, (iii) adopting modelling techniques to test the performance, robustness and economic viability of possible adaptation solutions, and (iv) innovating governance arrangements and principles needed to improve flood resilience in the Elster Creek catchment. Our research also provided valuable insight on how to operationalize interdisciplinary work in practice, highlighting the importance of sharing an impact agenda, taking a place-based approach, developing a common conceptual framework, and fostering a constructive team culture. This article is part of the theme issue ‘Urban flood resilience’.

Carbon (C) emissions from wildfires are a key terrestrial–atmosphere interaction that influences global atmospheric composition and climate. Positive feedbacks between climate warming and boreal wildfires are predicted based on top-down controls of fire weather and climate, but C emissions from boreal fires may also depend on bottom-up controls of fuel availability related to edaphic controls and overstory tree composition. Here we synthesized data from 417 field sites spanning six ecoregions in the northwestern North American boreal forest and assessed the network of interactions among potential bottom-up and top-down drivers of C emissions. Our results indicate that C emissions are more strongly driven by fuel availability than by fire weather, highlighting the importance of fine-scale drainage conditions, overstory tree species composition and fuel accumulation rates for predicting total C emissions. By implication, climate change-induced modification of fuels needs to be considered for accurately predicting future C emissions from boreal wildfires.

This paper presents a novel interdisciplinary and catchment-based approach for exploring urban flood resilience. Our research identified and developed a diverse set of adaptation measures for Elwood, a suburb in Melbourne, Australia, that is vulnerable to pluvial and coastal flooding. We drew on methods from social science, urban design and environmental engineering to gain integrated insights into the opportunities for Elwood to increase its flood resilience and urban liveability. Results showed that an appropriate balance of social, infrastructural and urban design responses would be required to retreat from, accommodate and protect against flood risk. These would also deliver broader benefits such as securing water supplies through harvested stormwater and mitigating extreme heat through greener landscapes. Our interdisciplinary approach demonstrated the value of (i) engaging with the community to understand their concerns, aspirations and adaptation ideas, (ii) exploring design measures that densify and use urban forms in ways that implement adaptation measures while responding to local context, (iii) adopting modelling techniques to test the performance, robustness and economic viability of possible adaptation solutions, and (iv) innovating governance arrangements and principles needed to improve flood resilience in the Elster Creek catchment. Our research also provided valuable insight on how to operationalize interdisciplinary work in practice, highlighting the importance of sharing an impact agenda, taking a place-based approach, developing a common conceptual framework, and fostering a constructive team culture. This article is part of the theme issue 'Urban flood resilience'.

The optimum duration of antimicrobial therapy would eradicate infection whilst minimising potential adverse drug effects to the patient. Australian and New Zealand infectious diseases (ID) and ICU specialists were surveyed regarding their recommended duration of antibiotic treatment for five common bacteraemic syndromes. A total of 239 clinicians responded to the survey (15.5% ICU and 84.5% ID). Overall, the most common reported durations were 7 (33.7%), 10 (25.9%) and 14 (26.0%) days, with 46% of responses recommending <=7 days. Most respondents (>75% for each characteristic) would not modify duration based on host characteristics such as patient age or co-morbidities. ID physicians recommended longer durations than ICU physicians for all five syndromes (ID, median 10, IQR 7-14, range 1-28 days; ICU, median 7, IQR 5-10, range 2-21 days). Across all respondents, the median (IQR) duration for each syndrome was: CVC-BSI, 7 (7-10) days; bacteraemic pneumonia, 7 (7-10) days; bacteraemic UTI, 10 (7-14) days; bacteraemic IAI, 7 (7-12) days; and bacteraemic SSTI, 10 (7-14) days. Marked variation exists amongst clinicians' recommended duration of antibiotic treatment for BSI. A proportion of clinicians recommend therapy of <=7 days at present (33.3-59.7% across scenarios). Patient characteristics are not strongly considered in the decision on therapy duration. This survey was undertaken as preparatory work for initiation of the BALANCE study, an ongoing randomised trial comparing 7 days with 14 days of therapy for BSI, providing an evidence base to inform best clinical treatment for this patient population.Copyright © 2019

Objectives: To characterize MDR Escherichia coli from bloodstream infections (BSIs) in Australia, New Zealand and Singapore. Method(s): We collected third-generation cephalosporin-resistant (3GC-R) E. coli from blood cultures in patients enrolled in a randomized controlled trial fromFebruary 2014 to August 2015. WGS was used to characterize antibiotic resistance genes, MLST, plasmids and phylogenetic relationships. Antibiotic susceptibility was determined using disc diffusion and Etest. Result(s): A total of 70 3GC-R E. coli were included, of which the majority were ST131 (61.4%). BSI was most frequently from a urinary source (69.6%), community associated (62.9%) and in older patients (median age 71 years). The median Pitt score was 1 and ICU admission was infrequent (3.1%). ST131 possessed more acquired resistance genes than non-ST131 (P=0.003). Clade C1/C2 ST131 predominated (30.2% and 53.5% of ST131, respectively) and these were all ciprofloxacin resistant. All clade A ST131 (n"6) were community associated. The predominant ESBL types were blaCTX-M (80.0%) and were strongly associated with ST131 (95% carried blaCTX-M), with the majority blaCTX-M-15. Clade C1 was associated with blaCTX-M-14 and blaCTX-M-27, whereas blaCTX-M-15 predominated in clade C2. Plasmid-mediated AmpC genes (mainly blaCMY-2) were frequent (17.1%) but were more common in non-ST131 (P<0.001) isolates from Singapore and Brisbane. Two strains carried both blaCMY-2 and blaCTX-M. The majority of plasmid replicon types were IncF. Conclusion(s): In a prospective collection of 3GC-R E. coli causing BSI, community-associated Clade C1/C2 ST131 predominate in associationwith blaCTX-M ESBLs, although a significant proportion of non-ST131 strains carried blaCMY-2.Copyright © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

Roughly 3% of the Earth's land surface burns annually, representing a critical exchange of energy and matter between the land and atmosphere via combustion. Fires range from slow smouldering peat fires, to low-intensity surface fires, to intense crown fires, depending on vegetation structure, fuel moisture, prevailing climate, and weather conditions. While the links between biogeochemistry, climate and fire are widely studied within Earth system science, these relationships are also mediated by fuels-namely plants and their litter-that are the product of evolutionary and ecological processes. Fire is a powerful selective force and, over their evolutionary history, plants have evolved traits that both tolerate and promote fire numerous times and across diverse clades. Here we outline a conceptual framework of how plant traits determine the flammability of ecosystems and interact with climate and weather to influence fire regimes. We explore how these evolutionary and ecological processes scale to impact biogeochemical and Earth system processes. Finally, we outline several research challenges that, when resolved, will improve our understanding of the role of plant evolution in mediating the fire feedbacks driving Earth system processes. Understanding current patterns of fire and vegetation, as well as patterns of fire over geological time, requires research that incorporates evolutionary biology, ecology, biogeography, and the biogeosciences.

Roughly 3% of the Earth's land surface burns annually, representing a critical exchange of energy and matter between the land and atmosphere via combustion. Fires range from slow smouldering peat fires, to low-intensity surface fires, to intense crown fires, depending on vegetation structure, fuel moisture, prevailing climate, and weather conditions. While the links between biogeochemistry, climate and fire are widely studied within Earth system science, these relationships are also mediated by fuels—namely plants and their litter—that are the product of evolutionary and ecological processes. Fire is a powerful selective force and, over their evolutionary history, plants have evolved traits that both tolerate and promote fire numerous times and across diverse clades. Here we outline a conceptual framework of how plant traits determine the flammability of ecosystems and interact with climate and weather to influence fire regimes. We explore how these evolutionary and ecological processes scale to impact biogeochemical and Earth system processes. Finally, we outline several research challenges that, when resolved, will improve our understanding of the role of plant evolution in mediating the fire feedbacks driving Earth system processes. Understanding current patterns of fire and vegetation, as well as patterns of fire over geological time, requires research that incorporates evolutionary biology, ecology, biogeography, and the biogeosciences.

Roughly 3% of the Earth’s land surface burns annually, representing a critical exchange of energy and matter between the land and atmosphere via combustion. Fires range from slow smouldering peat fires, to low-intensity surface fires, to intense crown fires, depending on vegetation structure, fuel moisture, prevailing climate, and weather conditions. While the links between biogeochemistry, climate and fire are widely studied within Earth system science, these relationships are also mediated by fuels—namely plants and their litter—that are the product of evolutionary and ecological processes. Fire is a powerful selective force and, over their evolutionary history, plants have evolved traits that both tolerate and promote fire numerous times and across diverse clades. Here we outline a conceptual framework of how plant traits determine the flammability of ecosystems and interact with climate and weather to influence fire regimes. We explore how these evolutionary and ecological processes scale to impact biogeochemical and Earth system processes. Finally, we outline several research challenges that, when resolved, will improve our understanding of the role of plant evolution in mediating the fire feedbacks driving Earth system processes. Understanding current patterns of fire and vegetation, as well as patterns of fire over geological time, requires research that incorporates evolutionary biology, ecology, biogeography, and the biogeosciences.

Long term planning of urban water infrastructure requires acknowledgement that transitions in the water system are driven by changes in the urban environment, as well as societal dynamics. Inherent to the complexity of these underlying processes is that the dynamics of a system's evolution cannot be explained by linear cause-effect relationships and cannot be predicted under narrow sets of assumptions. Planning therefore needs to consider the functional behaviour and performance of integrated flexible infrastructure systems under a wide range of future conditions. This paper presents the first step towards a new generation of integrated planning tools that take such an exploratory planning approach. The spatially explicit model, denoted DAnCE4Water, integrates urban development patterns, water infrastructure changes and the dynamics of socio-institutional changes. While the individual components of the DAnCE4Water model (i.e. modules for simulation of urban development, societal dynamics and evolution/performance of water infrastructure) have been developed elsewhere, this paper presents their integration into a single model. We explain the modelling framework of DAnCE4Water, its potential utility and its software implementation. The integrated model is validated for the case study of an urban catchment located in Melbourne, Australia.

Objectives: To define standardized endpoints to aid the design of trials that compare antibiotic therapies for bloodstream infections (BSI). Methods: Prospective studies, randomized trials or registered protocols comparing antibiotic therapies for BSI, published from 2005 to 2016, were reviewed. Consensus endpoints for BSI studies were defined using a modified Delphi process. Results: Different primary and secondary endpoints were defined for pilot (small-scale studies designed to evaluate protocol design, feasibility and implementation) and definitive trials (larger-scale studies designed to test hypotheses and influence clinical practice), as well as for Staphylococcus aureus and Gram-negative BSI. For pilot studies of S. aureus BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever, stable/improved Sequential Organ Failure Assessment (SOFA) score and clearance of blood cultures, with no microbiologically confirmed failure up to 90 days. For definitive S. aureus BSI studies, a primary outcome of success at 90 days was defined by survival and no microbiologically confirmed failure. For pilot studies of Gram-negative BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever and symptoms related to BSI source, stable or improved SOFA score and negative blood cultures. For definitive Gram-negative BSI studies, a primary outcome of survival at 90 days supported by a secondary outcome of success at day 7 (as previously defined) was agreed. Conclusions: These endpoints provide a framework to aid future trial design. Further work will be required to validate these endpoints with respect to patient-centred clinical outcomes. (C) 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

[Objectives] To define standardized endpoints to aid the design of trials that compare antibiotic therapies for bloodstream infections (BSI)., [Methods] Prospective studies, randomized trials or registered protocols comparing antibiotic therapies for BSI, published from 2005 to 2016, were reviewed. Consensus endpoints for BSI studies were defined using a modified Delphi process., [Results] Different primary and secondary endpoints were defined for pilot (small-scale studies designed to evaluate protocol design, feasibility and implementation) and definitive trials (larger-scale studies designed to test hypotheses and influence clinical practice), as well as for Staphylococcus aureus and Gram-negative BSI. For pilot studies of S. aureus BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever, stable/improved Sequential Organ Failure Assessment (SOFA) score and clearance of blood cultures, with no microbiologically confirmed failure up to 90 days. For definitive S. aureus BSI studies, a primary outcome of success at 90 days was defined by survival and no microbiologically confirmed failure. For pilot studies of Gram-negative BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever and symptoms related to BSI source, stable or improved SOFA score and negative blood cultures. For definitive Gram-negative BSI studies, a primary outcome of survival at 90 days supported by a secondary outcome of success at day 7 (as previously defined) was agreed., [Conclusions] These endpoints provide a framework to aid future trial design. Further work will be required to validate these endpoints with respect to patient-centred clinical outcomes.

© 2017 Australian Commission on Safety and Quality in Health Care Gram-negative bacteria that are resistant to antimicrobials, including carbapenems, have emerged as a significant global public health threat. Multidrug-resistant gram-negative bacteria, including carbapenemase-producing Enterobacteriaceae (CPE), place patients at risk of potentially untreatable infection. Australia has not reported a large number of CPE cases compared to Europe, North America, and the Middle East, creating an opportunity to prevent CPE from becoming established in Australia. An outbreak of Klebsiella pneumoniae carbapenemase in 2014 demonstrated there was variable testing, reporting, response to and communication of CPE. In response, the Australian Commission on Safety and Quality in Health Care formed a taskforce to assist health facilities to respond to the threat of CPE. Recommendations for state and territory health departments include coordinating a risk assessment, undertaking epidemiological and microbiological investigations, determining the requirement for control measures, and coordinating risk-communication activities. The response should take advice from experts in infectious diseases, microbiology, public health, infection prevention and control and epidemiologists. The guide aims to: • Alert healthcare professionals, health departments and hospital executives to the emerging threat of CPE in Australia• Recommend strategies to prevent, detect and contain CPE• Provide information and resources for hospital executives, healthcare professionals and consumers• Recommend laboratory screening and confirmation methods.The recommendations with rationale and commentary have been structured into sections depending on the burden of CPE in the health facility. The sections include: planning, preparing and prevention; CPE screening and surveillance; strategies to reduce CPE transmission; outbreak management; laboratory screening and confirmation methods.

Fires in the boreal forests of North America are generally stand-replacing, killing the majority of trees and initiating succession that may last over a century. Functional variation during succession can affect local surface energy budgets and, potentially, regional climate. Burn area across Alaska and Canada has increased in the last few decades and is projected to be substantially higher by the end of the 21st century because of a warmer climate with longer growing seasons. Here we simulated changes in forest composition due to altered burn area using a stochastic model of fire occurrence, historical fire data from national inventories, and succession trajectories derived from remote sensing. When coupled to an Earth system model, younger vegetation from increased burning cooled the high-latitude atmosphere, primarily in the winter and spring, with noticeable feedbacks from the ocean and sea ice. Results from multiple scenarios suggest that a doubling of burn area would cool the surface by 0.23 ± 0.09 °C across boreal North America during winter and spring months (December through May). This could provide a negative feedback to winter warming on the order of 3–5% for a doubling, and 14–23% for a quadrupling, of burn area. Maximum cooling occurs in the areas of greatest burning, and between February and April when albedo changes are largest and solar insolation is moderate. Further work is needed to integrate all the climate drivers from boreal forest fires, including aerosols and greenhouse gasses.

This paper provides guidance on how to identify and design the most suitable climate adaptation strategies for enhancing the liveability and flood resilience of urban catchments. It presents findings from a case study of Elwood, a coastal Melbourne suburb regularly affected by flooding. The research integrates social science, architecture and environmental engineering to co-develop technical, design and policy solutions that respond to the local community’s vision for the future and are robust under a range of future climate, population and urban development scenarios. The paper shows that ensuring a city’s flood resilience involves a range of measures to retreat from, adapt to and defend against flooding; this necessarily requires an integrated approach and interdisciplinary expertise to develop adaptation pathways that are grounded in community aspirations and priorities, inspired by novel design solutions and informed by modelling of performance, robustness and economic viability.

The city of Kiruna in Northern Sweden has become known for the need to relocate major parts of the city. Current and future mining activities in the world’s largest underground iron ore mine are the cause of land subsidence that requires relocation of substantial parts of the town including its water infrastructure. Figure 1 shows the area currently affected and projections thereof for the future. The process of relocating the city has started already and will continue for a few decades. It implies the construction of new urban areas and at the same time demolition in abandoned areas. With regard to the life span of water infrastructure, all actions taken now and in the near future will have an impact over five to ten decades. These circumstances place special demands on processes and technical solutions with regard to robustness, flexibility and mobility and require dealing with changes that cannot yet be foreseen., Urbanism, Architecture and The Built Environment

To find out whether food-producing animals (FPAs) are a source of extraintestinal expanded-spectrum cephalosporin-resistant Escherichia coli (ESCR-EC) infections in humans, Medline, Embase, and the Cochrane Database of Systematic Reviews were systematically reviewed. Thirty-four original, peer-reviewed publications were identified for inclusion. Six molecular epidemiology studies supported the transfer of resistance via whole bacterium transmission (WBT), which was best characterized among poultry in the Netherlands. Thirteen molecular epidemiology studies supported transmission of resistance via mobile genetic elements, which demonstrated greater diversity of geography and host FPA. Seventeen molecular epidemiology studies did not support WBT and two did not support mobile genetic element-mediated transmission. Four observational epidemiology studies were consistent with zoonotic transmission. Overall, there is evidence that a proportion of human extraintestinal ESCR-EC infections originate from FPAs. Poultry, in particular, is probably a source, but the quantitative and geographical extent of the problem is unclear and requires further investigation.

To the Editor—We thank Bonten and Mevius for their interest in our systematic review [1]. In their letter, they disagree with our finding that whole-bacterium transmission (WBT) of expanded-spectrum cephalosporin-resistant (ESCR) Escherichia coli between food-producing animals and humans likely contributes to the burden of human extraintestinal infections. We respectfully argue against 2 assumptions that underlie their assertion.

presented at the Applied Vision Association Christmas Meeting, Leuven, Belgium 19-20 December 2013

An integrated model system is based on downscaling from climate models, to wave climate and continental shelf models for tides and surge, to coastal models for waves and water levels, to beach levels and overtopping of sea defences and inundation. Present operational practice in the UK is described. The model system is applied to the prediction of flooding at Walcott on 9 November 2007. Inundation levels are predicted in reasonable agreement with those at certain residential properties in Walcott as reported by the occupants. The effect of time-varying and time-averaged overtopping discharge is considered. Sensitivity of overtopping and inundation to uncertainties in nearshore wave height and water level is analysed, with the greatest sensitivity being to water level. Extreme joint probability analysis is undertaken, showing the event to be close to a 1 in 100-year event. Finally, the effects of different rates of sea level rise and a climate change scenario are investigated for 2100; the simulations indicate that the return period of the equivalent 2007 event could reduce to less than 2 years with a 0.5m sea level rise.

Introduction: Bombesin (BBN) and BBN analogues have attracted much attention as high-affinity ligands for selective targeting of the gastrin-releasing peptide (GRP) receptor. GRP receptors are overexpressed in a variety of human cancers including prostate cancer. Radiolabeled BBN derivatives are promising diagnostic probes for molecular imaging of GRP receptor-expressing prostate cancer. This study describes the synthesis and radiopharmacological evaluation of various metabolically stabilized fluorobenzoylated bombesin analogues (BBN-1, BBN-2, BBN-3). Methods: Three fluorobenzoylated BBN analogues containing an aminovaleric (BBN-1, BBN-2), or an aminooctanoic acid linker (BBN-3) were tested in a competitive binding assay against 125I-[Tyr4]-BBN for their binding potency to the GRP receptor. Intracellular calcium release in human prostate cancer cells (PC3) was measured to determine agonistic or antagonistic profiles of fluorobenzoylated BBN derivatives. Bombesin derivative BBN-2 displayed the highest inhibitory potency toward GRP receptor (IC50 = 8.7 ± 2.2 nM) and was subsequently selected for radiolabeling with fluorine-18 (18F) through acylation with N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB). The radiopharmacological profile of 18F-labeled bombesin [18F]BBN-2 was evaluated in PC3 tumor-bearing NMRI nude mice involving metabolic stability studies, biodistribution experiments and dynamic small-animal PET studies. Results: All fluorobenzoylated BBN derivatives displayed high inhibitory potency toward the GRP receptor (IC50 = 8.7–16.7 nM), and all compounds exhibited antagonistic profiles as determined in an intracellular calcium release assay. The 18F-labeled BBN analogue [18F]BBN-2 was obtained in 30% decay-corrected radiochemical yield with high radiochemical purity N95% after semi-preparative HPLC purification. [18F]BBN-2 showed

Fires are a global phenomenon that impact climate and biogeochemical cycles, and interact with the biosphere, atmosphere and cryosphere. These impacts occur on a range of temporal and spatial scales and are difficult to quantify globally based solely on observations. Here we assess the role of fires in the climate system using model estimates of radiative forcing (RF) from global fires in pre-industrial, present day, and future time periods. Fire emissions of trace gases and aerosols are derived from Community Land Model simulations and then used in a series of Community Atmosphere Model simulations with representative emissions from the years 1850, 2000, and 2100. Additional simulations are carried out with fire emissions from the Global Fire Emission Database for a present-day comparison. These results are compared against the results of simulations with no fire emissions to compute the contribution from fires. We consider the impacts of fire on greenhouse gas concentrations, aerosol effects (including aerosol effects on biogeochemical cycles), and land and snow surface albedo. Overall, we estimate that pre-industrial fires were responsible for a RF of −1 W m−2 with respect to a pre-industrial climate without fires. The largest magnitude pre-industrial forcing from fires was the indirect aerosol effect on clouds (−1.6 W m−2). This was balanced in part by an increase in carbon dioxide concentrations due to fires (+0.83 W m−2). The RF of fires increases by 0.5 W m−2 from 1850 to 2000 and 0.2 W m−2 from 1850 to 2100 in the model representation from a combination of changes in fire activity and changes in the background environment in which fires occur, especially increases and decreases in the anthropogenic aerosol burden. Thus, fires play an important role in both the natural equilibrium climate and the climate perturbed by anthropogenic activity and need to be considered in future climate projections.

In several biomes, including croplands, wooded savannas, and tropical forests, many small fires occur each year that are well below the detection limit of the current generation of global burned area products derived from moderate resolution surface reflectance imagery. Although these fires often generate thermal anomalies that can be detected by satellites, their contributions to burned area and carbon fluxes have not been systematically quantified across different regions and continents. Here we developed a preliminary method for combining 1-km thermal anomalies (active fires) and 500 m burned area observations from the Moderate Resolution Imaging Spectroradiometer (MODIS) to estimate the influence of these fires. In our approach, we calculated the number of active fires inside and outside of 500 m burn scars derived from reflectance data. We estimated small fire burned area by computing the difference normalized burn ratio (dNBR) for these two sets of active fires and then combining these observations with other information. In a final step, we used the Global Fire Emissions Database version 3 (GFED3) biogeochemical model to estimate the impact of these fires on biomass burning emissions. We found that the spatial distribution of active fires and 500 m burned areas were in close agreement in ecosystems that experience large fires, including savannas across southern Africa and Australia and boreal forests in North America and Eurasia. In other areas, however, we observed many active fires outside of burned area perimeters. Fire radiative power was lower for this class of active fires. Small fires substantially increased burned area in several continental-scale regions, including Equatorial Asia (157%), Central America (143%), and Southeast Asia (90%) during 2001–2010. Globally, accounting for small fires increased total burned area by approximately by 35%, from 345 Mha/yr to 464 Mha/yr. A formal quantification of uncertainties was not possible, but sensitivity ana

A multi-drill automation project is described which has involved the development of a robust system for automating most of the functions on Caterpillar SKSS16 drill rigs for use in blasthole drilling. The key objectives were to develop a scalable, remotely operated system capable of controlling at least three production drills with a single driller. A wireless network solution was selected which contains three radios and uses the 802.11 b/g modulation. The system supports ad hoc mesh networks, and nodes were installed on the drills and automation communication trailers. The nodes on the trailers were then connected to the existing broadband. The prototype vision system used seven fixed cameras to allow the remote operator to gauge the performance and aspect of the drill, and proved to be robust and reliable. A new remote console with a similar layout to the prototype console was constructed. It was assumed that the drills would operate in automation mode most of the time and only one remote control console was employed for three drills. A custom built independent shutdown system was constructed using a programmable logic controller with an ethernet gateway. Automated drilling is currently being trialled in production at the West Angelas iron ore mine in the Pilbara region of Western Australia. Benefits of multi-drill automation have included a safer operating environment, production of a more stable hole, more accurate hole collar position, drilling of a more accurate hole angle and depth, less stress on the mast and chassis, reduced training time to follow site drilling standards, increase availability of drills, longer mean time between failures and improve blast outcomes., A multi-drill automation project is described which has involved the development of a robust system for automating most of the functions on Caterpillar SKSS16 drill rigs for use in blasthole drilling. The key objectives were to develop a scalable, remotely operated system capable of controlling at least three production drills with a single driller. A wireless network solution was selected which contains three radios and uses the 802.11 b/g modulation. The system supports ad hoc mesh networks, and nodes were installed on the drills and automation communication trailers. The nodes on the trailers were then connected to the existing broadband. The prototype vision system used seven fixed cameras to allow the remote operator to gauge the performance and aspect of the drill, and proved to be robust and reliable. A new remote console with a similar layout to the prototype console was constructed. It was assumed that the drills would operate in automation mode most of the time and only one remote control console was employed for three drills. A custom built independent shutdown system was constructed using a programmable logic controller with an ethernet gateway. Automated drilling is currently being trialled in production at the West Angelas iron ore mine in the Pilbara region of Western Australia. Benefits of multi-drill automation have included a safer operating environment, production of a more stable hole, more accurate hole collar position, drilling of a more accurate hole angle and depth, less stress on the mast and chassis, reduced training time to follow site drilling standards, increase availability of drills, longer mean time between failures and improve blast outcomes.

Experiments showing a seasonal variation of the nuclear decay rates of a number of different nuclei, and decay anomalies apparently related to solar flares and solar rotation, have suggested that the Sun may somehow be influencing nuclear decay processes. Recently, Cooper searched for such an effect in $^{238}$Pu nuclei contained in the radioisotope thermoelectric generators (RTGs) on board the Cassini spacecraft. In this paper we modify and extend Cooper's analysis to obtain constraints on anomalous decays of $^{238}$Pu over a wider range of models, but these limits cannot be applied to other nuclei if the anomaly is composition-dependent. We also show that it may require very high sensitivity for terrestrial experiments to discriminate among some models if such a decay anomaly exists, motivating the consideration of future spacecraft experiments which would require less precision., Comment: 8 pages, 4 figures (to appear in Astroparticle Physics)

Objectives: According to GLOBOSCAN 2008 the worldwide prostate cancer incidence rates will increase to about 1.7 million new cases per year in 2030. In recent years, bombesin and bombesin analogs have attracted much attention as high affinity and selectivity ligands for the gastrin-releasing peptide (GRP) receptor. The GRP receptor was found to be overexpressed and implicated in a variety of human tumors including prostate cancer. Radiolabeled bombesin and bombesin analogues belong to an interesting class of new diagnostic probes for molecular imaging of GRP receptor-expressing prostate cancer. This study describes the synthesis and radiopharmacological evaluation of a high affinity and metabolically stabilized 18F-labeled bombesin analog for PET imaging of GRP receptors in prostate cancer. Methods: Three modified bombesin analogs bearing an aminovaleric (BBN-1, BBN-2), or an aminooctanoic acid linker (BBN-3) were tested in a competitive binding assay against 125I-[Tyr4]-BBN for their binding to the GRP receptor. A calcium release assay in human prostate cancer cells (PC3) was performed to determine agonistic or antagonistic behaviour. The derivative with the highest affinity to GRP (BBN-2) was selected to be conjugated with the prosthetic labeling agent N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB) in borate buffer (pH=8.2) for 30 min at 40°C to synthesize the desired 18F-labeled bombesin analog. Tumor-targeting of [18F]BBN-2 was evaluated in PC3 tumor-bearing male nude mice with biodistribution experiments (mean ± SD) and dynamic small animal PET studies. Results: The competitive binding assay revealed IC50-values between 8.7 and 16.7 nM for BBN-1, BBN-2 and BBN-3 against 125I-[Tyr4]-BBN versus 3.0 nM for I-[Tyr4]-BBN. All three stabilized bombesin analogs are GRP receptor antagonists. 18F-labeled [18F]BBN-2 was prepared in 30% radiochemical yield (based upon [18F]SFB) within 80 min including HPLC purification, evaporation of HPLC eluent and formulation in 0.9%

UK coasts are subject to widespread erosion in part due to the cumulative effect of human intervention on soft coastlines, and further threatened due to more rapid change due to climate change, especially sea-level rise. At the same time, Shoreline Management now requires predictions of coastal evolution up to 100 years in the future. This leads to the challenge of predicting coastal geomorphic behaviour at the mesoscale (10 to 100 km and 10 to 100 years). Currently, this is often based on expert judgement. However, relevant components for mesoscale coastal simulation are emerging, including: (1) new methods for system-level analysis of coast, estuary and offshore landform behaviour, which include engineering and management interventions in a consistent manner to natural drivers; (2) well validated ‘bottom-up’ hydrodynamic and sediment transport models such as POLCOMS and TELEMAC; (3) operational ‘reduced complexity models’ of selected coastal landforms (e.g., cliffs (SCAPE), estuaries (ASMITA), saltmarsh (SLAMM)); and (4) growing observational datasets that allow data-driven approaches to coastal analysis and prediction. The iCOASST Project will use these components to develop and apply an integrated systems modelling framework for mesoscale coastal simulation as explained in this paper.

In several biomes, including croplands, wooded savannas, and tropical forests, many small fires occur each year that are well below the detection limit of the current generation of global burned area products derived from moderate resolution surface reflectance imagery. Although these fires often generate thermal anomalies that can be detected by satellites, their contributions to burned area and carbon fluxes have not been systematically quantified across different regions and continents. Here we developed a preliminary method for combining 1-km thermal anomalies (active fires) and 500 m burned area observations from the Moderate Resolution Imaging Spectroradiometer (MODIS) to estimate the influence of these fires. In our approach, we calculated the number of active fires inside and outside of 500 m burn scars derived from reflectance data. We estimated small fire burned area by computing the difference normalized burn ratio (dNBR) for these two sets of active fires and then combining these observations with other information. In a final step, we used the Global Fire Emissions Database version 3 (GFED3) biogeochemical model to estimate the impact of these fires on biomass burning emissions. We found that the spatial distribution of active fires and 500 m burned areas were in close agreement in ecosystems that experience large fires, including savannas across southern Africa and Australia and boreal forests in North America and Eurasia. In other areas, however, we observed many active fires outside of burned area perimeters. Fire radiative power was lower for this class of active fires. Small fires substantially increased burned area in several continental-scale regions, including Equatorial Asia (157%), Central America (143%), and Southeast Asia (90%) during 2001–2010. Globally, accounting for small fires increased total burned area by approximately by 35%, from 345 Mha/yr to 464 Mha/yr. A formal quantification of uncertainties was not possible, but sensitivity ana

vol. 69 no. 3, Senator Smathers (p.1). The E. T. Roux Library is shown above in one of those rare moments when it is being used exclusively for its intended purpose - a place of study (p.3). Mrs. Vivian Fusillo (p.4). Pick (p.5) -- Nelson (p.5). Is this the Willis Yak you're looking for, Professor Ogden? (p.6) / By Dick Bibler., Senator Smathers (p.1). The E. T. Roux Library is shown above in one of those rare moments when it is being used exclusively for its intended purpose - a place of study (p.3). Mrs. Vivian Fusillo (p.4). Pick (p.5) -- Nelson (p.5). Is this the Willis Yak you're looking for, Professor Ogden? (p.6) / By Dick Bibler., 1-6

vol. 69 no. 4, Barbara Mock (p.1) -- Pictured above are the thirty-three students who will begin their internship on Monday. For identification, see page six. (p.1). There's no telling where it would have ended if she hadn't been drafted (p.2) / By Crawford. FSC bookstore (p.3). HY Jordon Sobiloff (p.4) -- Jim Chios (p.4). Pictured above are six members of the Baseball Administration faculty. From left to right, top, Robert L. Finch, Richard Walsh, and Allen H. Russell. Bottom row: William Bergesch, W. B. Carswell, and W. D. Shilling. (p.5)., Barbara Mock (p.1) -- Pictured above are the thirty-three students who will begin their internship on Monday. For identification, see page six. (p.1). There's no telling where it would have ended if she hadn't been drafted (p.2) / By Crawford. FSC bookstore (p.3). HY Jordon Sobiloff (p.4) -- Jim Chios (p.4). Pictured above are six members of the Baseball Administration faculty. From left to right, top, Robert L. Finch, Richard Walsh, and Allen H. Russell. Bottom row: William Bergesch, W. B. Carswell, and W. D. Shilling. (p.5)., 1-6

This paper discusses the process steps for the production of sulphuric acid from sulphur dioxide gas. Following efficient cleaning and dehydration of metallurgical and decomposition gases, SO2 is oxidised to SO3 in contact with supported liquid-phase catalyst and the SO3 gas then reacts with a 1.5% H2O component of strong H2SO4. The catalyst is molten V in a V, K, Na, Cs, S, O solution on porous silica substrate. Details of single- and multi-catalyst bed oxidation and of single- and double-contact acid-making are discussed. Methods for the control and optimisation of acid-making are indicated, with special emphasis on SO2 oxidation efficiency. Other methods surveyed are: different scrubbing processes; regenerable processes such as amine absorb/desorb; and the Sulfacid, Peracidox (peroxide scrubbing), Petersen-Fattinger (lead chamber) and WSA (wet-gas sulphuric acid) processes., This paper discusses the process steps for the production of sulphuric acid from sulphur dioxide gas. Following efficient cleaning and dehydration of metallurgical and decomposition gases, SO2 is oxidised to SO3 in contact with supported liquid-phase catalyst and the SO3 gas then reacts with a 1.5% H2O component of strong H2SO4. The catalyst is molten V in a V, K, Na, Cs, S, O solution on porous silica substrate. Details of single- and multi-catalyst bed oxidation and of single- and double-contact acid-making are discussed. Methods for the control and optimisation of acid-making are indicated, with special emphasis on SO2 oxidation efficiency. Other methods surveyed are: different scrubbing processes; regenerable processes such as amine absorb/desorb; and the Sulfacid, Peracidox (peroxide scrubbing), Petersen-Fattinger (lead chamber) and WSA (wet-gas sulphuric acid) processes.