Autumn MIST 2019

Maria-Theresia Walach, Greg Hunt, Alexandra Fogg and Alexander Bader report on the rescheduled Autumn MIST Meeting for 2019, organized by the MIST Council, which took place in January 2020

Second generation anticoagulant rodenticide residues in barn owls 2018

The current report is the fourth in a series of annual reports that describe the monitoring of second generation anticoagulant rodenticide (SGAR) liver residues in barn owls Tyto alba in Britain. This work is an element of an overarching monitoring programme undertaken to track the outcomes of stewardship activities associated with the use of anticoagulant rodenticides. The barn owl is used for exposure monitoring as it is considered a sentinel for species that are generalist predators of small mammals in rural areas. The specific work reported here is the measurement of liver SGAR residues in 100 barn owls that died in 2018 in locations across Britain. The residue data are compared with those from 395 barn owls that died between 2006 and 2012 (hereafter termed baseline years), prior to changes in anticoagulant rodenticide (AR) authorisations and onset of stewardship. As in the baseline years, the compounds detected most frequently in barn owls that died in 2018 were bromadiolone, difenacoum and brodifacoum. Overall, 87% of the owls had detectable liver residues of one or more SGAR. The metrics to be used for stewardship monitoring are reported below in terms of differences between owls that died in 2018 and in baseline years. Numbers of barn owls containing detectable residues of flocoumafen and difethialone. There was no significant difference in the proportion of barn owls with detectable liver residues of flocoumafen between the baseline years and 2018. There was a significantly higher proportion of barn owls with detectable liver residues of difethialone in 2018 compared to baseline years (8% vs 0.3% ). The ratio of birds with ”low” (100 ng/g wet wt.) concentrations for any single SGAR or for ∑SGARs. There was no significant difference between barn owls from baseline years and from 2018 for any individual compound or for summed SGARs (∑SGARs), although a decrease in the proportion of birds with “high” difenacoum residues approached significance. Average concentrations of brodifacoum, difenacoum, bromadiolone and ∑SGARs in the cohort of owls with “low” residues (100 ng/g ww). There was no significant difference between barn owls from baseline years and from 2018 in the concentrations of either “low” or “high” residues for bromadiolone, difenacoum (data tested statistically only for “low residues”), all residues summed (∑SGARs), or “high” brodifacoum residues. The median concentration of “low” brodifacoum residues was higher in birds from 2018 than in baseline years. Overall, there were few differences in liver SGAR accumulation between barn owls that died in baseline years and in 2018. The lack of significant reductions in SGAR residues in barn owls in 2018 suggests that full implementation of stewardship since 2016 has yet to result in a reduction in exposure of barn owls to SGARs

Evaluating transport in irregular pore networks

A general approach for investigating transport phenomena in porous media is presented. This approach has the capacity to represent various kinds of irregularity in porous media without the need for excessive detail or computational effort. The overall method combines a generalized effective medium approximation (EMA) with a macroscopic continuum model in order to derive a transport equation with explicit analytical expressions for the transport coefficients. The proposed form of the EMA is an anisotropic and heterogeneous extension of Kirkpatrick's EMA which allows the overall model to account for microscopic alterations in connectivity (with the locations of the pores and the orientation and length of the throat) as well as macroscopic variations in transport properties. A comparison to numerical results for randomly generated networks with different properties is given, indicating the potential for this methodology to handle cases that would pose significant difficulties to many other analytical models

Morphologies of AGN host galaxies using HST/ACS in the CDFS-GOODS field

Using HST/ACS images in four bands F435W, F606W, F775W and F850LP, we identify optical counterparts to the X-ray sources in the Chandra Deep Field South in the GOODS South field. A detailed study has been made of these sources to study their morphological types. We use methods like decomposition of galaxy luminosity profiles, color maps and visual inspection of 192 galaxies which are identified as possible optical counterparts of Chandra X-ray sources in the CDFS-GOODS field. We find that most moderate luminosity AGN hosts are bulge dominated in the redshift range (z \approx 0.4-1.3), but not merging/interacting galaxies. This implies probable fueling of the moderate luminosity AGN by mechanisms other than those merger driven.Comment: pdflatex, accepted in ApSS. revisions in tex

Emergence of Drug Resistance Is Associated with an Increased Risk of Death among Patients First Starting HAART

BACKGROUND: The impact of the emergence of drug-resistance mutations on mortality is not well characterized in antiretroviral-naïve patients first starting highly active antiretroviral therapy (HAART). Patients may be able to sustain immunologic function with resistant virus, and there is limited evidence that reduced sensitivity to antiretrovirals leads to rapid disease progression or death. We undertook the present analysis to characterize the determinants of mortality in a prospective cohort study with a median of nearly 5 y of follow-up. The objective of this study was to determine the impact of the emergence of drug-resistance mutations on survival among persons initiating HAART. METHODS AND FINDINGS: Participants were antiretroviral therapy naïve at entry and initiated triple combination antiretroviral therapy between August 1, 1996, and September 30, 1999. Marginal structural modeling was used to address potential confounding between time-dependent variables in the Cox proportional hazard regression models. In this analysis resistance to any class of drug was considered as a binary time-dependent exposure to the risk of death, controlling for the effect of other time-dependent confounders. We also considered each separate class of mutation as a binary time-dependent exposure, while controlling for the presence/absence of other mutations. A total of 207 deaths were identified among 1,138 participants over the follow-up period, with an all cause mortality rate of 18.2%. Among the 679 patients with HIV-drug-resistance genotyping done before initiating HAART, HIV-drug resistance to any class was observed in 53 (7.8%) of the patients. During follow-up, HIV-drug resistance to any class was observed in 302 (26.5%) participants. Emergence of any resistance was associated with mortality (hazard ratio: 1.75 [95% confidence interval: 1.27, 2.43]). When we considered each class of resistance separately, persons who exhibited resistance to non-nucleoside reverse transcriptase inhibitors had the highest risk: mortality rates were 3.02 times higher (95% confidence interval: 1.99, 4.57) for these patients than for those who did not exhibit this type of resistance. CONCLUSIONS: We demonstrated that emergence of resistance to non-nucleoside reverse transcriptase inhibitors was associated with a greater risk of subsequent death than was emergence of protease inhibitor resistance. Future research is needed to identify the particular subpopulations of men and women at greatest risk and to elucidate the impact of resistance over a longer follow-up period

Interaction of amyloid and tau on cortical microstructure in cognitively unimpaired adults

INTRODUCTION: Neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion-weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment. METHODS: Using neuroimaging (NODDI and T1-weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys® CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (Aβ)42/Aβ40 and phosphorylated tau (p-tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E ε4. RESULTS: We observed a significant CSF Aβ42/Aβ40 × p-tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. The directionality of these interactive effects indicated: (1) among individuals with lower CSF p-tau, greater amyloid burden was associated with higher cortical NDI; and (2) individuals with greater amyloid and p-tau burden had lower cortical NDI, consistent with cortical neurodegenerative changes. DISCUSSION: NDI is a particularly sensitive marker for early cortical changes that occur prior to gross atrophy or development of cognitive impairment

Second generation anticoagulant rodenticide residues in barn owls 2019

The fifth in a series of annual reports describing the magnitude of second generation anticoagulant rodenticide (SGAR) liver residues in barn owls Tyto alba in Britain

Duration of androgen suppression before radiotherapy for localized prostate cancer: Radiation therapy oncology group randomized clinical trial 9910

Purpose To determine whether prolonged androgen suppression (AS) duration before radiotherapy improves survival and disease control in prostate cancer. Patients and Methods One thousand five hundred seventy-nine men with intermediate-risk prostate cancer were randomly assigned to 8 weeks of AS followed by radiotherapy with an additional 8 weeks of concurrent AS (16 weeks total) or to 28 weeks of AS followed by radiotherapy with an additional 8 weeks of AS (36 weeks total). The trial sought primarily to detect a 33% reduction in the hazard of prostate cancer death in the 28-week assignment. Time-to-event end points are reported for up to 10 years of follow-up. Results There were no between-group differences in baseline characteristics of 1,489 eligible patients with follow-up. For the 8- and 28-week assignments, 10-year disease-specific survival rates were 95% (95% CI, 93.3% to 97.0%) and 96% (95% CI, 94.6% to 98.0%; hazard ratio [HR], 0.81; P = .45), respectively, and 10-year overall survival rates were66%(95% CI, 62.0% to 69.9%) and67%(95% CI, 63.0% to 70.8%; HR, 0.95; P = .62), respectively. For the 8- and 28-week assignments, 10-year cumulative incidences of locoregional progression were 6% (95% CI, 4.3% to 8.0%) and 4% (95% CI, 2.5% to 5.7%; HR, 0.65; P = .07), respectively; 10-year distant metastasis cumulative incidences were 6% (95% CI, 4.0% to 7.7%) and 6% (95% CI, 4.0% to 7.6%; HR, 1.07; P = .80), respectively; and 10-year prostate-specific antigen-based recurrence cumulative incidences were 27% (95% CI, 23.1% to 29.8%) and 27% (95% CI, 23.4% to 30.3%; HR, 0.97; P = .77), respectively. Conclusion Extending AS duration from 8 weeks to 28 weeks before radiotherapy did not improve outcomes. A lower than expected prostate cancer death rate reduced ability to detect a between-group difference in disease-specific survival. The schedule of 8 weeks of AS before radiotherapy plus 8 weeks of AS during radiotherapy remains a standard of care in intermediate-risk prostate cancer

Second generation anticoagulant rodenticide residues in barn owls 2017

CEH contract report to the Campaign for Responsible Rodenticide Use (CRRU) UK. A wide range of avian and mammalian predators and scavengers in rural Britain is known to be exposed to Second Generation Anticoagulant Rodenticides (SGARs). The barn owl Tyto alba is a sentinel for species that are generalist predators of small mammals in rural areas in the UK and monitoring of liver SGAR residues in barn owls has been adopted as an element of the monitoring undertaken as part of anticoagulant rodenticide stewardship. Monitoring of liver SGAR residues in some 100 barn owls per year is conducted in support of stewardship and annually collected data are compared with those from 395 barn owls that died between 2006 and 2012 (hereafter termed baseline years), prior to the 2016 changes in anticoagulant rodenticide (AR) authorisations and onset of stewardship. The rationale for using data on SGAR residues in barn owls that died between 2006 and 2012 as a baseline was that all measurements had been made using the same analytical techniques, there had been little clear change in exposure over that time period, and the data were the most recent available. The aim of the current study was to measure SGAR exposure in barn owls in 2017. As in the baseline years, the compounds detected most frequently in barn owls that died in 2017 were bromadiolone, difenacoum and brodifacoum. Overall, 90% of the owls had detectable liver residues of one or more SGAR. The metrics to be used for stewardship monitoring are reported below in terms of differences between owls that died in 2017 and in baseline years. Numbers of barn owls containing detectable residues of flocoumafen and difethialone. There was no significant difference in the proportion of barn owls with detectable liver residues of either flocoumafen or difethialone between the baseline years and 2017. The ratio of birds with ”low” (100 ng/g wet wt.) concentrations for any single SGAR or for ∑SGARs. There was no significant difference between barn owls from baseline years and from 2017 for any individual compound or for summed SGARs (∑SGARs) Average concentrations of brodifacoum, difenacoum, bromadiolone and ∑SGARs in the cohort of owls with “low” residues (100 ng/g wet wt.). There was no significant difference between barn owls from baseline years and from 2017 in the concentrations of either “low” or “high” residues for bromadiolone, difenacoum and brodifacoum, or for all residues summed (∑SGARs). Although not statistically significant, the median and 75th percentile values of “low residues” of most compounds and ∑SGARs were lower in 2017 [and 2016] than in the baseline years Overall, the lack of statistically significant differences in SGAR accumulation by barn owls in 2017 compared within baseline years suggests that full implementation of stewardship since 2016 has yet to be reflected by a detectable general reduction in exposure of barn owls

Second generation anticoagulant rodenticide residues in barn owls 2020

The current report is the sixth in a series of annual reports that describe the monitoring of second generation anticoagulant rodenticide (SGAR) liver residues in barn owls Tyto alba in Britain. This work is an element of an overarching monitoring programme undertaken to track the outcomes of stewardship activities associated with the use of anticoagulant rodenticides. The barn owl is used for exposure monitoring as it is considered a sentinel for species that are generalist predators of small mammals in rural areas. The specific work reported here is the measurement of liver SGAR residues in 100 barn owls that died in 2020 at locations across Britain. The residue data are compared with those from 395 barn owls that died between 2006 and 2012 (hereafter termed baseline years), prior to changes in anticoagulant rodenticide (AR) authorisations and onset of stewardship. As in the baseline years, the compounds detected most frequently in barn owls that died in 2020 were brodifacoum, bromadiolone, and difenacoum. Overall, 88% of the owls had detectable liver residues of one or more SGAR. Numbers of barn owls containing detectable residues of flocoumafen and difethialone. There was no significant difference in the proportion of barn owls with detectable liver residues of flocoumafen between the baseline years and 2020. There was a significantly higher proportion of barn owls with detectable liver residues of difethialone in 2020 compared to baseline years (5% vs 0.3%) but it was lower than in some of the intervening years (2016-2019). The ratio of birds with “low” (100 ng/g wet wt.) concentrations for any single SGAR or for ∑SGARs. There were significantly higher proportion of birds from 2020 with “high” concentrations of brodifacoum and summed SGARs (ƩSGARs) detected in their livers compared to baseline years. Average concentrations of brodifacoum, difenacoum, bromadiolone and ∑SGARs in the cohort of owls with “low” residues (100 ng/g wet wt.). There was no significant difference between barn owls from baseline years and from 2020 in the concentrations of either “low” or “high” residues for all residues summed (∑SGARs), bromadiolone and difenacoum, or “high” brodifacoum residues. The median concentration of “low” brodifacoum residues was higher in birds from 2020 than in baseline years. Overall, there were few differences in liver SGAR accumulation between barn owls that died in baseline years and in 2020, the eception being a potential increase brodifacoum residues. The lack of significant reductions in SGAR residues in barn owls in 2020 suggests that full implementation of stewardship since 2018 has yet to result in a statistically significant reduction in exposure of barn owls to SGARs