Integration of biological effects, fish histopathology and contaminant measurements for the assessment of fish health: A pilot application in Irish marine waters

This study investigates the use of a weight of evidence (WOE) approach to evaluate fish health status and biological effects (BEs) of contaminants for assessment of ecosystem health and discusses its potential application in support of the Marine Strategy Framework Directive (MSFD). External fish disease, liver histopathology and several BEs of contaminant exposure including 7-ethoxy resorufin O-de-ethylase (EROD), acetylcholinesterase (AChE), bile metabolites, vitellogenin (VTG) and alkali labile phosphates (ALP) were measured in two flatfish species from four locations in Ireland. Contaminant levels in fish were generally low with PCBs in fish liver below OSPAR environmental assessment criteria (EAC). There were consistencies with low PCB levels, EROD and PAH bile metabolite levels detected in fish. Dab from Cork, Dublin and Shannon had the highest relative prevalence of liver lesions associated with the carcinogenic pathway. An integrated biomarker response (IBR) showed promise to be useful for evaluation of environmental risk, although more contaminant parameters in liver are required for a full assessment with the present study

A novel albumin gene mutation (R222I) in familial dysalbuminemic hyperthyroxinemia.

CONTEXT: Familial dysalbuminemic hyperthyroxinemia, characterized by abnormal circulating albumin with increased T4 affinity, causes artefactual elevation of free T4 concentrations in euthyroid individuals. OBJECTIVE: Four unrelated index cases with discordant thyroid function tests in different assay platforms were investigated. DESIGN AND RESULTS: Laboratory biochemical assessment, radiolabeled T4 binding studies, and ALB sequencing were undertaken. (125)I-T4 binding to both serum and albumin in affected individuals was markedly increased, comparable with known familial dysalbuminemic hyperthyroxinemia cases. Sequencing showed heterozygosity for a novel ALB mutation (arginine to isoleucine at codon 222, R222I) in all four cases and segregation of the genetic defect with abnormal biochemical phenotype in one family. Molecular modeling indicates that arginine 222 is located within a high-affinity T4 binding site in albumin, with substitution by isoleucine, which has a smaller side chain predicted to reduce steric hindrance, thereby facilitating T4 and rT3 binding. When tested in current immunoassays, serum free T4 values from R222I heterozygotes were more measurably abnormal in one-step vs two-step assay architectures. Total rT3 measurements were also abnormally elevated. CONCLUSIONS: A novel mutation (R222I) in the ALB gene mediates dominantly inherited dysalbuminemic hyperthyroxinemia. Susceptibility of current free T4 immunoassays to interference by this mutant albumin suggests likely future identification of individuals with this variant binding protein.This work was supported by funding from the Wellcome Trust (Grant 100585/Z/12/Z, to N.S., Grant 095564/Z/11/Z, to K.C.) and National Institute for Health Research Cambridge Biomedical Research Centre (to C.M., and M.G.).This is the final published version of the article. It was originally published in The Journal of Clinical Endocrinology & Metabolism (Nadia Schoenmakers, Carla Moran, Irene Campi, Maura Agostini, Olivia Bacon, Odelia Rajanayagam, John Schwabe, Sonia Bradbury, Timothy Barrett, Frank Geoghegan, Maralyn Druce, Paolo Beck-Peccoz, Angela O'Toole, Penelope Clark, Michelle Bignell, Greta Lyons, David Halsall, Mark Gurnell, Krishna Chatterjee. J Clin Endocrinol Metab 2014 Jul 19;99(7):E1381-6. Epub 2014 Mar 19. http://dx.doi.org/10.1210/jc.2013-4077). A correction to this article was issued because the CC-BY licence was not present on the final published paper (http://dx.doi.org/10.1210/jc.2015-1656)

Prevalence of and factors associated with MDR Neisseria gonorrhoeae in England and Wales between 2004 and 2015: analysis of annual cross-sectional surveillance surveys.

Objectives: To describe trends in prevalence, susceptibility profile and risk factors for MDR Neisseria gonorrhoeae (MDR-NG) in England and Wales. Methods: Isolates from 16 242 gonorrhoea episodes at sexual health clinics within the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) underwent antimicrobial susceptibility testing. MDR-NG was defined as resistance to ceftriaxone, cefixime or azithromycin, plus at least two of penicillin, ciprofloxacin and spectinomycin. Trends in resistance are presented for 2004-15; prevalence and logistic regression analyses for MDR-NG cover the period of the most recent treatment guideline (ceftriaxone plus azithromycin), 2011-15. Results: Between 2004 and 2015, the proportion of N. gonorrhoeae isolates fully susceptible to all antimicrobial classes fell from 80% to 46%, with the proportion resistant to multiple (two or more) classes increasing from 7.3% to 17.5%. In 2011-15, 3.5% of isolates were MDR-NG, most of which were resistant to cefixime (100% in 2011, decreasing to 36.9% in 2015) and/or azithromycin (4.2% in 2011, increasing to 84.3% in 2015). After excluding azithromycin-resistant isolates, modal azithromycin MICs were higher in MDR versus non-MDR isolates (0.5 versus 0.125 mg/L), with similar results for ceftriaxone (modal MICs 0.03 versus ≤0.002 mg/L). After adjustment for confounders, MDR-NG was more common among isolates from heterosexual men, although absolute differences in prevalence were small [4.6% versus 3.3% (MSM) and 2.5% (women)]. Conclusions: N. gonorrhoeae is becoming less susceptible to available antimicrobials. Since 2011, a minority of isolates were MDR-NG; however, MICs of azithromycin or ceftriaxone (first-line therapies) for many of these were elevated. These findings highlight the importance of continued antimicrobial stewardship for gonorrhoea

A Review of the Tools Used for Marine Monitoring in the UK: Combining Historic and Contemporary Methods with Modeling and Socioeconomics to Fulfill Legislative Needs and Scientific Ambitions

Marine environmental monitoring is undertaken to provide evidence that environmental management targets are being met. Moreover, monitoring also provides context to marine science and over the last century has allowed development of a critical scientific understanding of the marine environment and the impacts that humans are having on it. The seas around the UK are currently monitored by targeted, impact-driven, programmes (e.g., fishery or pollution based monitoring) often using traditional techniques, many of which have not changed significantly since the early 1900s. The advent of a new wave of automated technology, in combination with changing political and economic circumstances, means that there is currently a strong drive to move toward a more refined, efficient, and effective way of monitoring. We describe the policy and scientific rationale for monitoring our seas, alongside a comprehensive description of the types of equipment and methodology currently used and the technologies that are likely to be used in the future. We contextualize the way new technologies and methodologies may impact monitoring and discuss how whole ecosystems models can give an integrated, comprehensive approach to impact assessment. Furthermore, we discuss how an understanding of the value of each data point is crucial to assess the true costs and benefits to society of a marine monitoring programme

Pharmacogenomic associations of adverse drug reactions in asthma:systematic review and research prioritisation

We would like to thank the NIHR Collaboration for Leadership in Applied Health Research and Care North West Coast (CLAHRC) for funding Amanda McKenna’s internship, and Charlotte Kings MPhil, and the members of the PiCA consortia for their help in completing the survey. U. Potočnik, K. Repnik and V. Berce were supported by SysPharmPedia grant, co-financed by Ministry of Education, Science and Sport of the Republic of Slovenia Author information These authors contributed equally: Charlotte King, Amanda McKenna These authors jointly supervised this work: Ian Sinha, Daniel B. HawcuttPeer reviewedPublisher PD

Crop Updates - 2003 Weeds

This session covers Thirty four papers from different authors INTRODUCTION INTEGRATED WEED MANAGEMENT IWM system studies/demonstration sites Six years of IWM investigation – what does it tell us? Bill Roy, Agricultural Consulting and Research Services Pty Ltd Long term herbicide resistance site, the final chapter, Peter Newman and Glen Adam, Department of Agriculture Management of skeleton weed (chondrilla juncea) in a cropping rotation in Western Australia, J. R. Peirce and B. J. Rayner, Department of Agriculture WEED BIOLOGY AND COMPETITION Annual ryegrass seedbanks: The good, the bad and the ugly, Kathryn J. Steadman1, Amanda J. Ellery2 and Sally C. Peltzer3 , 1WA Herbicide Resistance Initiative, UWA, 2CSIRO Plant Industry, 3 Department of Agriculture Annual ryegrass seeds after-ripen faster during a hot summer, Kathryn J. Steadman1, Gavin P. Bignell1 and Amanda J. Ellery2, 1WA Herbicide Resistance Initiative, UWA, 2CSIRO Plant Industry Predicting annual ryegrass dormancy from climatic variables, Amanda Ellery, Andrew Moore, Sandy Nedelkos, Ross Chapman, CSIRO Plant Industry Removing dormancy in annual ryegrass seeds for early herbicide resistance testing, Kathryn J. Steadman and Mechelle J. Owen, WA Herbicide Resistance Initiative, UWA Annual ryegrass germination responds to nitrogen, Amanda Ellery1, Simone Dudley1 and Robert Gallagher2, 1CSIRO Plant Industry, 2Washington State University The agro-ecology of Malva parviflora (small flowered mallow), Pippa J. Michael, Kathryn J. Steadman and Julie A. Plummer, Western Australia Herbicide Resistance Initiative, School of Plant Biology, University of Western Australia The looming threat of wild radish, Peter Newman, Department of Agriculture IWM TOOLS Double knock, how close can we go? Peter Newman and Glen Adam, Department of Agriculture Double knock herbicide effect on annual ryegrass, Catherine Borger, Abul Hashem and Nerys Wilkins, Department of Agriculture Tactical techniques for managing Annual Ryegrass, Sally Peltzer1, Alex Douglas1, Fran Hoyle1, Paul Matson1 and Michael Walsh2 Department of Agriculture and 2Western Australian Herbicide Resistance Initiative. Weed control through soil inversion, Sally Peltzer, Alex Douglas and Paul Matson, Department of Agriculture The burning issues of annual ryegrass seed control, Darren Chitty and Michael Walsh, Western Australian Herbicide Resistance Initiative, UWA No sign of chaff-cart resistant ryegrass! David Ferris, WA Herbicide Resistance Initiative UWA PACKAGES AND MODELLING Conserving glyphosate susceptibility – modelling past, present and future us. Paul Neve1, Art Diggle2, Patrick Smith3 and Stephen Powles1 ,1Western Australian Herbicide Resistance Initiative, School of Plant Biology, University of Western Australia, 2Department of Agriculture, 3CSIRO Sustainable Ecosystems WEEDEM: A program for predicting weed emergence in Western Australia, Michael Walsh,1 David Archer2, James Eklund2 and Frank Forcella2, 1Western Australia Herbicide Resistance Initiative, UWA, 2USDA-Agricultural Research Service, 803 Iowa Avenue, Morris, MN 56267, USA Weed and herbicide management for long term profit: A workshop, Alister Draper1 and Rick Llewellyn12, 1WA Herbicide Resistance Initiative, 2School of Agricultural and Resource Economics, University of Western Australia HERBICIDE RESISTANCE Alternative herbicides for control of triazine and diflufenican multiple resistant wild radish, Aik Cheam1, Siew Lee1, David Nicholson1 and Mike Clarke2 1Department of Agriculture, Western Australia, 2Bayer CropScience Resistance of wild mustard biotype to ALS-inhibiting herbicides in WA Wheatbelt, Abul Hashem, Department of Agriculture Glyphosate-resistant ryegrass biotypes in the WA wheatbelt, Abul Hashem, Catherine Borger and Nerys Wilkins, Department of Agriculture Implications of herbicide rates for resistance management, Paul Neve, Western Australian Herbicide Resistance Initiative, University of Western Australia Putting a price on herbicide resistance, Rick Llewellyn, School of Agricultural and Resource Economics/WA Herbicide Resistance Initiative, University of Western Australia Herbicide resistance from over the fence: Mobility and management, Debbie Allena, Rick Llewellynb, aUniversity of Western Australia, 4th year student, 2002. Mingenew-Irwin Group, bSchool of Agricultural and Resource Economics/Western Australia Herbicide Resistance Initiative, University of Western Australia HERBICIDE TOLERANCE Herbicide tolerance of new barley varieties, Harmohinder S. Dhammu and Terry Piper, Department of Agriculture Herbicide tolerance of new lupins, Harmohinder S. Dhammu, Terry Piper and David Nicholson, Department of Agriculture Herbicide tolerance of new field pea varieties, Harmohinder S. Dhammu, Terry Piper and David Nicholson, Department of Agriculture Herbicide tolerance of new lentil varieties, H.S. Dhammu, T.J. Piper and L.E. Young, Department of Agriculture HERBICIDES – NEW PRODUCTS/PRODUCT USES; USE Kill half leaf ryegrass with Spray.Seed® at night, Peter Newman and Glenn Adam, Department of Agriculture CLEARFIELD™ wheat to control hard-to-kill weeds, Abul Hashem, Catherine Borger and Nerys Wilkins, Department of Agriculture Diuron, a possible alternative to simazine pre-emergent in lupins, Peter Newman and Glenn Adam, Department of Agriculture Dual Gold® soft on barley, soft on weeds in dry conditions, Peter Newman and Glenn Adam, Department of Agriculture Dual Gold® soft on lupins, soft on ryegrass in dry conditions, Peter Newman and Glenn Adam, Department of Agricultur

Gain of MYC underlies recurrent trisomy of the MYC chromosome in acute promyelocytic leukemia

The leukemogenic effects of Myc drive recurrent trisomy in a mouse model of acute myeloid leukemia

Pharmacogenomic associations of adverse drug reactions in asthma: systematic review and research prioritisation

A systematic review of pharmacogenomic studies capturing adverse drug reactions (ADRs) related to asthma medications was undertaken, and a survey of Pharmacogenomics in Childhood Asthma (PiCA) consortia members was conducted. Studies were eligible if genetic polymorphisms were compared with suspected ADR(s) in a patient with asthma, as either a primary or secondary outcome. Five studies met the inclusion criteria. The ADRs and polymorphisms identified were change in lung function tests (rs1042713), adrenal suppression (rs591118), and decreased bone mineral density (rs6461639) and accretion (rs9896933, rs2074439). Two of these polymorphisms were replicated within the paper, but none had external replication. Priorities from PiCA consortia members (representing 15 institution in eight countries) for future studies were tachycardia (SABA/LABA), adrenal suppression/crisis and growth suppression (corticosteroids), sleep/behaviour disturbances (leukotriene receptor antagonists), and nausea and vomiting (theophylline). Future pharmacogenomic studies in asthma should collect relevant ADR data as well as markers of efficacy

Report of the Working Group of Biological Effects

The Working Group on Biological Effects of Contaminants (WGBEC) investigates the biological effects of contaminants in the marine environment. The group provides research and increases the understanding of contaminant interactions and effects, including the development of inte-grated biological effects monitoring strategies, which are used to support international research and monitoring. The WGBEC has contributed significantly to the implementation and harmonization of tech-niques that can be used to evaluate the biological effects of pollutants in national monitoring programmes. An overview of national effect-based monitoring programmes of Member States is provided with the aim to support European countries and Regional Seas Conventions on their implementation. A summary of the national effects-based monitoring programmes has been pro-vided by twelve European countries represented at the WGBEC meetings. The adoption of bio-logical effects monitoring can differ widely and comparisons between approaches and the choice of biological effects methods used acts as an important tool. A summary of the main findings is presented. Furthermore, OSPAR's Hazardous Substances and Eutrophication Committee (HASEC) has en-couraged contracting parties to perform targeted biological effects monitoring to enhance the assessment of contaminants in sediment and biota towards the OSPAR QSR2023. WGBEC mem-bers contributed to the integrated biological effects approach assessment by providing data from their national monitoring activities to produce maps and figures to enable interpretations. Revision of the biological effects methods, including new techniques and developments, and the quality assurance of existing methods are core activities for the WGBEC, which require continu-ous discussion and evaluation by the group. Activities include the production of new ICES TIMES documents as well as intercalibration exercises to ensure Member States are providing comparable data for national monitoring. To this end, intercalibration exercises were performed under the BEQUALM programme for two of the more commonly used biological effects meth-ods, including micronucleus formation in mussel haemocytes and PAH metabolites in fish bile. These intercalibrations were successful despite identifying some variation in reported values be-tween laboratories. Further intercalibration exercises are planned and the WGBEC strongly sup-port the need for such quality assurance. In addition to the national monitoring activities and the different methods and approaches for determining the effects of contaminants on biological systems, the WGBEC was interested in discussing some key questions related to the potential impacts of contaminants to marine life. These questions included: the direct and indirect effects of natural and synthetic particles; how climate change and acidification parameters can interact with contaminants and influence bioa-vailability and effect; whether the structure of marine communities can be used to indicate con-taminant exposure; to provide guidance on performing risk assessments for contaminants of emerging concern; and to evaluate the effects of contaminants in marine sediments and whether current sediment toxicity tests are adequate. In addition, and as a wider concept, the linkages between contaminants in the marine environment and human health were also described.S

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients