Anticoagulant rodenticides in red kites (Milvus milvus) in Britain in 2017 and 2018

Second generation anticoagulant rodenticides (SGARs) can be toxic to all mammals and birds. Various studies have shown that, in Britain, there is widespread exposure to SGARs in a diverse range of predatory mammals and birds, including red kites (Milvus milvus) which scavenge dead rats, a target species for rodent control. The Wildlife Incident Monitoring Scheme (WIIS) and the Predatory Bird Monitoring Scheme (PBMS) have shown that some mortalities result from this secondary exposure. In the present study, we analysed liver SGAR residues in 77 red kites that had been found dead in Britain in either 2017 or 2018. The carcasses were submitted to and necropsied by the Disease Risk Analysis and Health Surveillance (DRAHS) programme, the PBMS, the WIIS for England & Wales, the WIIS for Scotland and the Raptor Health Scotland study; the livers from the kites were subsequently analysed for SGAR residues. All the organisations are partners in the WILDCOMS network that promotes collaboration among surveillance schemes that monitor disease and contaminants in vertebrate wildlife. All of the 66 kites from England & Wales and 10 of the 11 red kites from Scotland had detectable liver residues of at least one SGAR. When considering the sample of kites as a whole, brodifacoum, difenacoum and bromadiolone were each detected in 73, 71 and 60 kites, respectively. Difethialone was found in 11 individuals while flocoumafen was detected in only one bird. Sum liver SGAR concentrations ranged between non-detected and 1218 ng/g wet wt. (arithmetic mean: 246 ng/g, median 154 ng/g). Post-mortem examinations indicated that 13 (16.8%) of red kites examined had internal haemorrhaging that was not associated with detectable trauma and had detectable liver SGAR concentrations. These birds had sum SGAR liver concentrations that ranged from 135 ng/g wet weight to 1218 ng/g wet weight. SGARs were considered a contributory cause of death in these cases. The stewardship scheme for anticoagulant rodenticides came fully into force in mid-2016 as re-registration of products for use in the UK was completed. A key aim is to reduce exposure of non-target wildlife to anticoagulant rodenticides but stewardship also aims to maintain efficacious rat control and so the number and density of AR-contaminated rats may remain unchanged. However, diligent searching, removal and safe disposal of poisoned rats, as promoted by stewardship, might be expected to reduce the availability of poisoned dead rats to red kites [and other scavengers] and thereby reduce the proportion of birds that are exposed and/or the magnitude of exposure. Concomitant with stewardship was a relaxation of the indoor use only restriction previously applied to brodifacoum, flocoumafen and difethialone, the three most acutely toxic SGARs. Any consequent increase in outdoor use of these three SGARs could increase the risk of secondary exposure in red kites. We therefore compared the data in the current report with that collected in 2015 and 2016 to determine if there was any evidence of a change in pattern or magnitude of exposure in red kites that might be connected to stewardship and/or change in usage restriction. The proportion of red kites exposed to SGARs in 2015 (90.6%), 2016 (89.6%) 2017 (96,4%) and 2018 (100%) was always 90% or more; the higher percentages in 2017 and 2018 were principally due to a greater proportion of birds from Scotland containing residues. Brodifacoum and difenacoum were the most prevalent compounds (89% of red kites across the four years for each compound) along with bromadiolone (75%). On average, there were residues of three different SGARs in each kite liver. There was no significant difference between years in liver sum (Σ) SGAR concentrations. We investigated if there was a change between years in the exposure of red kites to brodifacoum, flocoumafen and difethialone, the compounds for which indoor only usage restrictions were relaxed in 2016. To enable statistical analysis of data on residue prevalence, it was necessary to pool the data into two-year blocks. Data on presence/absence of detectable brodifacoum, flocoumafen or difethialone residues were therefore compared for 2015/16 (pre and year of implementation of change in usage restriction) and 2017/18 (post-change in usage restriction). The proportion of red kites with detectable residues was 82% (50 out of 61 red kites) in 2015/16 but significantly higher (95%; 73 out of 77 red kites) in 2017/18. However, there was also an increase [albeit not statistically significant] in the proportion of red kites with detectable liver difenacoum or bromadiolone residues (90% in 2015/16 vs. 97% in 2017/18). Therefore, these data may simply reflect an increase in the prevalence of exposure to SGARs generally rather than any effect of change in usage restriction. There was no difference between the four years in the summed magnitude of liver brodifacoum, difethialone and flocoumafen concentrations. The percentage of red kites examined that were diagnosed as birds in which SGARs were implicated as a contributory cause of death did not differ significantly between individual years nor show a significant trend across the years; the overall average across the four years was 22%. However, if data were pooled by pairs of years (2017/8 vs 2015/16), the proportion of red kites for which SGARs were implicated as a contributory cause of death was lower (18%) in 2017/18 than in 2015/16 (33%) for red kites from England & Wales. Our findings do not indicate that there has been any reduction in exposure in red kites to SGARs following implementation of stewardship, in terms of either the proportion of individuals exposed or the magnitude of residues detected. There is some evidence (depending upon the statistical approach used) that the proportion of red kites in which SGARs were implicated as a contributory mortality factor has decreased in more recent years. There was no clear evidence that relaxation of usage restrictions on brodifacoum, difethialone and flocoumafen has altered the pattern of residue accumulation in red kites to date

2022 Update of the consensus on the rational use of antithrombotics and thrombolytics in Veterinary Critical Care (CURATIVE) Domain 6: Defining rational use of thrombolytics

Objectives To systematically review available evidence and establish guidelines related to the use of thrombolytics for the management of small animals with suspected or confirmed thrombosis. Design PICO (Population, Intervention, Control, and Outcome) questions were formulated, and worksheets completed as part of a standardized and systematic literature evaluation. The population of interest included dogs and cats (considered separately) and arterial and venous thrombosis. The interventions assessed were the use of thrombolytics, compared to no thrombolytics, with or without anticoagulants or antiplatelet agents. Specific protocols for recombinant tissue plasminogen activator were also evaluated. Outcomes assessed included efficacy and safety. Relevant articles were categorized according to level of evidence, quality, and as to whether they supported, were neutral to, or opposed the PICO questions. Conclusions from the PICO worksheets were used to draft guidelines, which were subsequently refined via Delphi surveys undertaken by the Consensus on the Rational Use of Antithrombotics and Thrombolytics in Veterinary Critical Care (CURATIVE) working group. Results Fourteen PICO questions were developed, generating 14 guidelines. The majority of the literature addressing the PICO questions in dogs is experimental studies (level of evidence 3), thus providing insufficient evidence to determine if thrombolysis improves patient-centered outcomes. In cats, literature was more limited and often neutral to the PICO questions, precluding strong evidence-based recommendations for thrombolytic use. Rather, for both species, suggestions are made regarding considerations for when thrombolytic drugs may be considered, the combination of thrombolytics with anticoagulant or antiplatelet drugs, and the choice of thrombolytic agent. Conclusions Substantial additional research is needed to address the role of thrombolytics for the treatment of arterial and venous thrombosis in dogs and cats. Clinical trials with patient-centered outcomes will be most valuable for addressing knowledge gaps in the field

Second generation anticoagulant rodenticide residues in red kites 2020

Second generation anticoagulant rodenticides (SGARs) can be toxic to all mammals and birds if consumed. Various studies have shown that, in Britain, there is widespread exposure to SGARs in a diverse range of predatory mammals and birds, including red kites (Milvus milvus) which scavenge dead rats, a target species for rodent control. The Wildlife Incident Investigation Scheme1 (WIIS) and the Predatory Bird Monitoring Scheme (PBMS) have shown that some mortalities result from this secondary exposure. In the present study, we analysed liver SGAR residues in 25 red kites that had been found dead in Britain in 2020. The carcasses were submitted to and necropsied by the Disease Risk Analysis and Health Surveillance (DRAHS) programme, the PBMS, the WIIS for England & Wales, the WIIS for Scotland and the Raptor Health Scotland study. All the organisations are partners in the WILDCOMS (Wildlife Disease & Contaminant Monitoring & Surveillance Network) network that promotes collaboration among surveillance schemes that monitor disease and contaminants in vertebrate wildlife in the UK. The UK Rodenticide Stewardship Regime began to come into force in mid-2016 as reregistration of products for use in the UK was approved by the HSE; full implementation of the scheme was in early 2018. The key aim of this stewardship initiative is to support competence among all SGAR users, a potential benefit of this may be the reduced exposure of non-target wildlife to anticoagulant rodenticides. However, the number and density of SGAR-contaminated rats may remain unchanged although diligent searching, removal and safe disposal of poisoned rats, as promoted by the stewardship regime, might be expected to reduce the availability of poisoned dead rats to red kites (and other scavengers) and thereby reduce the proportion of birds that are exposed and/or the magnitude of exposure. Concomitant with the stewardship scheme was a relaxation of the indoor-use-only-restriction previously applied to brodifacoum, flocoumafen and difethialone, the three most acutely toxic SGARs. Any consequent increase in outdoor use of these three SGARs could increase the risk of secondary exposure in red kites. We therefore compared the data in the current report with that collected in 2015 and 2016 to determine if there was any evidence of a change in pattern or magnitude of exposure in red kites that might be connected to stewardship and/or change in usage restriction. All but one of the 21 red kites from England & Wales and two of the four red kites from Scotland had detectable liver residues of at least one type of SGAR. When considering the sample of red kites as a whole, brodifacoum, difenacoum and bromadiolone were each detected in 21, 19 and 17 red kites, respectively. Difethialone was found in four individuals while flocoumafen was detected in one bird. The proportion of analysed red kites exposed to SGARs in 2015 (91%), 2016 (90%) 2017 (96%), 2018 (100%) 2019 (91%) and 2020 (88%) was similar at circa 88% or more; the higher percentages in 2017 and 2018 were principally due to a greater proportion of birds from Scotland containing residues than observe in other years. Difenacoum, brodifacoum, and bromodialone were the most prevalent compounds (detected in 86%, 85%, and 76% of red kites across the six years for each compound, respectively). On average, there were detectable residues of three different SGARs in each red kite liver likely demonstrating multiple exposures. Sum liver SGAR concentrations in birds from 2020 ranged between non-detectable and 1086 ng/g wet weight (arithmetic mean: 371 ng/g wet weight, median 307 ng/g wet weight). Necropsy examinations indicated that three (13%) of red kites examined had internal haemorrhaging that was not associated with detectable trauma and also had detectable liver SGAR concentrations. These birds had sum SGAR liver concentrations of 663, 905 and 1086 ng/g wet weight. SGARs were considered a contributory cause of death resulting from unspecified use in these cases. SGARs were a contributory cause of death in 17% of the red kite cases examined across all six years. Over the period 2015 to 2020, a reduction has been observed in the percentage of red kites examined that were diagnosed as birds in which SGARs were implicated as a contributory cause of death. However, given that the WIIS scheme specifically examines suspected poisoning incidents, it is likely that poisoned birds are over represented in this sample compared to the population as a whole in all six years. Due to these reasons, caution should be used when interpreting evident changes in mortality rates due to the sampling protocols used in this study that may lead to over reporting of mortality rates, and those rates being subject to variations in relative contribution of the WIIS and PBMS to each year’s sample. There was no statistically significant difference between years, irrespective of cause of death, in median summed SGAR residues, and no evidence that the magnitude of accumulated summed SGAR residues has changed consistently over time. Sum bromadiolone and difenacoum concentrations were lower in 2016 than 2015, however, there was no difference for sum brodifacoum, flocoumafen, and difethialone concentrations. Data on presence/absence of detectable brodifacoum, flocoumafen or difethialone residues were compared for 2015/16 and 2017/18/19/20. The proportion of red kites with detectable residues of these three SGARs was 82% in 2015/16 and similar proportions were observed in 2017/18/19/20 (86%). Similarly, there was no significant difference in the proportion of red kites with detectable liver difenacoum or bromadiolone residues (90% in 2015/16 vs. 93% in 2017/18/19/20). Since the implementation of the stewardship regime no difference in exposure pattern relating to active ingredient has been detected. Our findings do not indicate that there has been a broad scale change in exposure in red kites to SGARs following implementation of stewardship in terms of either the proportion of the sample exposed or the magnitude of sum SGARs residues detected. There is some evidence (depending upon the statistical approach used) that the proportion of red kites in which SGARs were implicated as a contributory mortality factor has decreased in more recent years. Alternative approaches to monitoring SGARs in red kites could be considered that analyses a random but representative sample, and as part of such a programme there may also be value in monitoring SGARs in the blood of tracked individuals. There was no clear evidence that relaxation of usage restrictions on brodifacoum, difethialone and flocoumafen has altered the pattern of residues for these compounds in red kites to date. However, data following full implementation of the rodenticide stewardship scheme is currently limited to four years

Anticoagulant rodenticides in red kites (Milvus milvus) in Britain 2015

Second generation anticoagulant rodenticides (SGARs) can be toxic to all mammals and birds. Various studies have shown that, in Britain, there is widespread exposure to SGARs in a diverse range of predatory mammals and birds, including red kites (Milvus milvus) which scavenge dead rats, a target species for rodent control. The Wildlife Incident Monitoring Scheme (WIIS) and the Predatory Bird Monitoring Scheme (PBMS) have shown that some mortalities result from this secondary exposure. The aim of the current study was to assess the scale and severity of exposure to SGARs (as assessed from the presence of liver SGAR residues) in red kites found dead in Britain in 2015. Carcasses, typically found by members of the public, were submitted for examination and analysis either to the Institute of Zoology’s Disease Risk Analysis and Health Surveillance programme (DRAHS) or to the Centre for Ecology & Hydrology’s Predatory Bird Monitoring Scheme, partners in the WILDCOMS network. We also report the results of SGAR analysis of red kites from England, Wales and Scotland that died in 2015 and analysed by the WIIS, who are also partners of the WILDCOMS network. Eighteen red kites from England & Wales were necropsied by either the DRAHS or the PBMS and the livers of the birds were analysed for SGARs by the PBMS. All had detectable liver residues of difenacoum and brodifacoum, and most also contained detectable liver bromadiolone residues. Difethialone was less frequently detected and flocoumafen was not detected in any birds. The presence of detectable brodifacoum residues in all birds may partly reflect the predominance of adult birds in the 2015 sample but may also indicate a growing prevalence of exposure to this compound. The percentage of red kites found by the PBMS to contain brodifacoum has increased since 2010 although any influence of age on this trend has not yet been examined. Sum liver SGAR concentrations in the 18 kites ranged between 50 and 1266 ng/g wet wt. (arithmetic mean: 463 ng/g). Post-mortems indicated that 7 of the kites had internal hemorrhaging that was not associated with detectable trauma; these birds typically had elevated sum SGAR liver concentrations. On the basis of these two factors, it is considered probable that SGARs were a contributory cause of death in these birds. The exposure pattern observed in 8 red kites from England & Wales analysed by the WIIS was very similar to that observed in birds analysed by the PBMS, with detectable liver residues of difenacoum and brodifacoum in all birds and bromadiolone in most. SGARs were assessed to be a contributory cause of death in two birds. Thus, of the 26 red kites from England & Wales analysed overall, SGARs were considered to be implicated in the deaths of 9 (35%). Residue data were available through the WIIS for 6 red kites from Scotland that died in 2015. Three kites (50%) had liver residues of at least two SGARs (bromadiolone and difenacoum); brodifacoum was also detected in one of these kites. SGARs were assessed to be a contributory cause of death in the bird that had residues of three SGARs. The data, although sample size is small, suggest that exposure of kites to SGARs may have been less marked in Scotland than in England & Wales in 2015, as has been found for other species

Tomato: a crop species amenable to improvement by cellular and molecular methods

Tomato is a crop plant with a relatively small DNA content per haploid genome and a well developed genetics. Plant regeneration from explants and protoplasts is feasable which led to the development of efficient transformation procedures. In view of the current data, the isolation of useful mutants at the cellular level probably will be of limited value in the genetic improvement of tomato. Protoplast fusion may lead to novel combinations of organelle and nuclear DNA (cybrids), whereas this technique also provides a means of introducing genetic information from alien species into tomato. Important developments have come from molecular approaches. Following the construction of an RFLP map, these RFLP markers can be used in tomato to tag quantitative traits bred in from related species. Both RFLP's and transposons are in the process of being used to clone desired genes for which no gene products are known. Cloned genes can be introduced and potentially improve specific properties of tomato especially those controlled by single genes. Recent results suggest that, in principle, phenotypic mutants can be created for cloned and characterized genes and will prove their value in further improving the cultivated tomato.

Intercalibration of the barrel electromagnetic calorimeter of the CMS experiment at start-up

Calibration of the relative response of the individual channels of the barrel electromagnetic calorimeter of the CMS detector was accomplished, before installation, with cosmic ray muons and test beams. One fourth of the calorimeter was exposed to a beam of high energy electrons and the relative calibration of the channels, the intercalibration, was found to be reproducible to a precision of about 0.3%. Additionally, data were collected with cosmic rays for the entire ECAL barrel during the commissioning phase. By comparing the intercalibration constants obtained with the electron beam data with those from the cosmic ray data, it is demonstrated that the latter provide an intercalibration precision of 1.5% over most of the barrel ECAL. The best intercalibration precision is expected to come from the analysis of events collected in situ during the LHC operation. Using data collected with both electrons and pion beams, several aspects of the intercalibration procedures based on electrons or neutral pions were investigated

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Measurement of the Lambda(b) cross section and the anti-Lambda(b) to Lambda(b) ratio with Lambda(b) to J/Psi Lambda decays in pp collisions at sqrt(s) = 7 TeV

The Lambda(b) differential production cross section and the cross section ratio anti-Lambda(b)/Lambda(b) are measured as functions of transverse momentum pt(Lambda(b)) and rapidity abs(y(Lambda(b))) in pp collisions at sqrt(s) = 7 TeV using data collected by the CMS experiment at the LHC. The measurements are based on Lambda(b) decays reconstructed in the exclusive final state J/Psi Lambda, with the subsequent decays J/Psi to an opposite-sign muon pair and Lambda to proton pion, using a data sample corresponding to an integrated luminosity of 1.9 inverse femtobarns. The product of the cross section times the branching ratio for Lambda(b) to J/Psi Lambda versus pt(Lambda(b)) falls faster than that of b mesons. The measured value of the cross section times the branching ratio for pt(Lambda(b)) > 10 GeV and abs(y(Lambda(b))) < 2.0 is 1.06 +/- 0.06 +/- 0.12 nb, and the integrated cross section ratio for anti-Lambda(b)/Lambda(b) is 1.02 +/- 0.07 +/- 0.09, where the uncertainties are statistical and systematic, respectively.Comment: Submitted to Physics Letters

Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at sqrt(s) = 7 TeV

A search is presented for physics beyond the standard model (BSM) in final states with a pair of opposite-sign isolated leptons accompanied by jets and missing transverse energy. The search uses LHC data recorded at a center-of-mass energy sqrt(s) = 7 TeV with the CMS detector, corresponding to an integrated luminosity of approximately 5 inverse femtobarns. Two complementary search strategies are employed. The first probes models with a specific dilepton production mechanism that leads to a characteristic kinematic edge in the dilepton mass distribution. The second strategy probes models of dilepton production with heavy, colored objects that decay to final states including invisible particles, leading to very large hadronic activity and missing transverse energy. No evidence for an event yield in excess of the standard model expectations is found. Upper limits on the BSM contributions to the signal regions are deduced from the results, which are used to exclude a region of the parameter space of the constrained minimal supersymmetric extension of the standard model. Additional information related to detector efficiencies and response is provided to allow testing specific models of BSM physics not considered in this paper.Comment: Replaced with published version. Added journal reference and DO

Measurement of isolated photon production in pp and PbPb collisions at sqrt(sNN) = 2.76 TeV

Isolated photon production is measured in proton-proton and lead-lead collisions at nucleon-nucleon centre-of-mass energies of 2.76 TeV in the pseudorapidity range |eta|<1.44 and transverse energies ET between 20 and 80 GeV with the CMS detector at the LHC. The measured ET spectra are found to be in good agreement with next-to-leading-order perturbative QCD predictions. The ratio of PbPb to pp isolated photon ET-differential yields, scaled by the number of incoherent nucleon-nucleon collisions, is consistent with unity for all PbPb reaction centralities.Comment: Submitted to Physics Letters