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Shellfish aquaculture often uses large amounts of plastic equipment and has been suggested as a potential source of microplastic contamination in the marine environment. To determine the influence of shellfish aquaculture on microplastic concentrations in bivalves and their environment, we compared microplastic particle (MP) concentrations in Manila clams Venerupis philippinarum and Pacific oysters Crassostrea gigas grown on commercial shellfish beaches with those in individuals of the same species grown on nearby non-aquaculture beaches in 6 regions of coastal British Columbia, Canada. MP concentrations did not differ between shellfish aquaculture and non-aquaculture sites for either bivalve species, sediment, or water samples. Plastic presence differed by site and oysters on sites with many synthetic anti-predator nets contained significantly, yet marginally, more MPs than those on sites without (0.05 vs. 0.03 g-1 dry-tissue weight on average). However, analysis of suspected MPs using Fourier-transform infrared spectroscopy indicated a predominance of fibres from textiles (including nylon and polyester), which are not typically used in shellfish aquaculture, suggesting that this may be caused by the larger average body weight of oysters grown at non-aquaculture sites rather than by the degradation of aquaculture infrastructure.

Biofouling communities were examined at five depths at two salmon farms (Doctor Islets (DI), Wicklow Point (WP)) in British Columbia, Canada from April/May to October 2020. In addition, various water quality parameters were measured and the jellyfish numbers were quantified. Biofouling communities were mainly composed of Mollusca (primarily Mytilus spp.), arthropods (mostly harpacticoids), and hydroids (predominantly Obelia sp.), while jellyfish samples were made up mostly of medusa-form Obelia sp. At DI, all variables except ammonia were associated with biofouling counts, all variables except depth were associated with hydroid biomass, while only temperature, dissolved oxygen, ammonia, and nitrate were associated with jellyfish. At WP, all variables except phosphate and silica were associated with biofouling counts, only depth was associated with hydroid biomass, and only ammonia was associated with jellyfish. Insights into what environmental variables are correlated with biofouling organisms and jellyfish may assist with the development of effective mitigation strategies.

Species interactions can influence key ecological processes that support community assembly and composition. For example, coralline algae encompass extensive diversity and may play a major role in regime shifts from kelp forests to urchin-dominated barrens through their role in inducing invertebrate larval metamorphosis and influencing kelp spore settlement. In a series of laboratory experiments, we tested the hypothesis that different coralline communities facilitate the maintenance of either ecosystem state by either promoting or inhibiting early recruitment of kelps or urchins. Coralline algae significantly increased red urchin metamorphosis compared with a control, while they had varying effects on kelp settlement. Urchin metamorphosis and density of juvenile canopy kelps did not differ significantly across coralline species abundant in both kelp forests and urchin barrens, suggesting that recruitment of urchin and canopy kelps does not depend on specific corallines. Non-calcified fleshy red algal crusts promoted the highest mean urchin metamorphosis percentage and showed some of the lowest canopy kelp settlement. In contrast, settlement of one subcanopy kelp species was reduced on crustose corallines, but elevated on articulated corallines, suggesting that articulated corallines, typically absent in urchin barrens, may need to recover before this subcanopy kelp could return. Coralline species differed in surface bacterial microbiome composition; however, urchin metamorphosis was not significantly different when microbiomes were removed with antibiotics. Our results clarify the role played by coralline algal species in kelp forest community assembly and could have important implications for kelp forest recovery., (© 2023 The Authors. Journal of Phycology published by Wiley Periodicals LLC on behalf of Phycological Society of America.)

Ocean acidification upwelling events and the resulting lowered aragonite saturation state of seawater have been linked to high mortality of marine bivalve larvae in hatcheries. Major oyster seed producers along North America's west coast have mitigated impacts via seawater pH buffering (e.g., addition of soda ash). However, little consideration has been given to whether such practice may impact the larval microbiome, with potential carry-over effects on immune competency and disease susceptibility in later-life stages. To investigate possible impacts, Pacific oysters ( Crassostrea gigas ) were reared under soda ash pH buffered or ambient pH seawater conditions for the first 24 h of development. Both treatment groups were then reared under ambient pH conditions for the remainder of the developmental period. Larval microbiome, immune status (via gene expression), growth, and survival were assessed throughout the developmental period. Juveniles and adults arising from the larval run were then subjected to laboratory-based disease challenges to investigate carry-over effects. Larvae reared under buffered conditions showed an altered microbiome, which was still evident in juvenile animals. Moreover, reduced survival was observed in both juveniles and adults of the buffered group under a simulated marine heatwave and Vibrio exposure compared with those reared under ambient conditions. Results suggest that soda ash pH buffering during early development may compromise later-life stages under stressor conditions, and illustrate the importance of a long-view approach with regard to hatchery husbandry practices and climate change mitigation. IMPORTANCE Shellfish industries are threatened worldwide by recurrent summer mortality events. Such incidences are often associated with Vibrio disease outbreaks, and thus, it is critical that animals are able to mount sufficient immune responses. The oyster immune system is linked to the microbiome which is laid down during early developmental stages. Consequently, shellfish hatcheries play a key role with regard to shaping the immune competency of later-life stages. This study represents the first in-depth examination of whether the adoption of seawater pH buffering practice by hatcheries for mitigation of ocean acidification may alter the larval microbiome, and thus, have repercussions for adult susceptibility to summer mortality events. Findings demonstrate that even minimal buffering results in a changed microbiome which is paralleled by increased mortality of later-life stages under Vibrio and temperature stressors, highlighting the importance of the hatchery environment with regard to shaping resilience to summer mortality events.

Anthropogenic particles (APs) generated from both natural and synthetic materials are widespread in the aquatic environment and contaminate seafood products, including shellfish. Depuration, involving the placement of filter-feeding shellfish in clean water for a period of time, often several days, is used to reduce contaminant concentrations, but the practicality of its use by the shellfish industry for APs has not yet been examined. In the present study, cultured adult Pacific oysters (Crassostrea gigas) were depurated for 10 days in a facility with limited airflow and filtered seawater. On average, there was a 73 % reduction in oyster AP concentration after 5 days, but no further reduction at 10 days, potentially due to the difficulty in depurating some particles or to re-contamination from the experimental environment. Long-term feasibility for industry will depend on future guidelines for safe AP consumption levels and the practicality and financial feasibility of creating and running clean facilities., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Nine-banded armadillos (Dasypus novemcinctus) are naturally infected with Mycobacterium leprae and are implicated in the zoonotic transmission of leprosy in the United States. In Mexico, the existence of such a reservoir remains to be characterized. We describe a wild armadillo infected by M. leprae in the state of Nuevo León, Mexico.

Calcium channels (CCs), a group of ubiquitously expressed membrane proteins, are involved in many pathophysiological processes of protozoan parasites. Our understanding of CCs in cell signaling, organelle function, cellular homeostasis, and cell cycle control has led to improved insights into their structure and functions. In this article, we discuss CCs characteristics of five major protozoan parasites Plasmodium, Leishmania, Toxoplasma, Trypanosoma, and Cryptosporidium. We provide a comprehensive review of current antiparasitic drugs and the potential of using CCs as new therapeutic targets. Interestingly, previous studies have demonstrated that human CC modulators can kill or sensitize parasites to antiparasitic drugs. Still, none of the parasite CCs, pumps, or transporters has been validated as drug targets. Information for this review draws from extensive data mining of genome sequences, chemical library screenings, and drug design studies. Parasitic resistance to currently approved therapeutics is a serious and emerging threat to both disease control and management efforts. In this article, we suggest that the disruption of calcium homeostasis may be an effective approach to develop new anti-parasite drug candidates and reduce parasite resistance., (© 2021 Wiley Periodicals LLC.)

SARS-CoV-2, the virus that causes COVID-19 consists of several enzymes with essential functions within its proteome. Here, we focused on repurposing approved and investigational drugs/compounds. We targeted seven proteins with enzymatic activities known to be essential at different stages of the viral cycle including PLpro, 3CLpro, RdRP, Helicase, ExoN, NendoU, and 2'-O-MT. For virtual screening, energy minimization of a crystal structure of the modeled protein was carried out using the Protein Preparation Wizard (Schrodinger LLC 2020-1). Following active site selection based on data mining and COACH predictions, we performed a high-throughput virtual screen of drugs and investigational molecules (n = 5903). The screening was performed against viral targets using three sequential docking modes (i.e., HTVS, SP, and XP). Virtual screening identified ∼290 potential inhibitors based on the criteria of energy, docking parameters, ligand, and binding site strain and score. Drugs specific to each target protein were further analyzed for binding free energy perturbation by molecular mechanics (prime MM-GBSA) and pruning the hits to the top 32 candidates. The top lead from each target pool was further subjected to molecular dynamics simulation using the Desmond module. The resulting top eight hits were tested for their SARS-CoV-2 anti-viral activity in-vitro. Among these, a known inhibitor of protein kinase C isoforms, Bisindolylmaleimide IX (BIM IX), was found to be a potent inhibitor of SARS-CoV-2. Further, target validation through enzymatic assays confirmed 3CLpro to be the target. This is the first study that has showcased BIM IX as a COVID-19 inhibitor thereby validating our pipeline., (Copyright © 2021. Published by Elsevier Inc.)

Varicella and zoster, produced by varicella-zoster virus (VZV), are associated with an increased risk of stroke that may be due to persistent inflammation and hypercoagulability. Because substance P is associated with inflammation, hypercoagulability, and atherosclerotic plaque rupture that may contribute to increased stroke risk after VZV infection, we measured serum substance P in simian varicella virus-infected rhesus macaques. We found significantly increased and persistent serum substance P concentrations during varicella and zoster compared with pre-inoculation, supporting the hypothesis that VZV-induced increases in serum substance P may contribute to increased stroke risk associated with VZV infection.

Zika virus (ZIKV) exhibits a tropism for brain tumor cells and has been used as an oncolytic virus to target brain tumors in mice with modest effects on extending median survival. Recent studies have highlighted the potential for combining virotherapy and immunotherapy to target cancer. We postulated that ZIKV could be used as an adjuvant to enhance the long-term survival of mice with malignant glioblastoma and generate memory T-cells capable of providing long-term immunity against cancer remission. To test this hypothesis mice bearing malignant intracranial GL261 tumors were subcutaneously vaccinated with irradiated GL261 cells previously infected with the ZIKV. Mice also received intracranial injections of live ZIKV, irradiation attenuated ZIKV, or irradiated GL261 cells previously infected with ZIKV. Long-term survivors were rechallenged with a second intracranial tumor to examine their immune response and look for the establishment of protective memory T-cells. Mice with subcutaneous vaccination plus intracranial irradiation attenuated ZIKV or intracranial irradiated GL261 cells previously infected with ZIKV exhibited the greatest extensions to overall survival. Flow cytometry analysis of immune cells within the brains of long-term surviving mice after tumor rechallenge revealed an increase in the number of T-cells, including CD4+ and tissue-resident effector/ effector memory CD4+ T-cells, in comparison to long-term survivors that were mock-rechallenged, and in comparison to naïve untreated mice challenged with intracranial gliomas. These results suggest that ZIKV can serve as an adjuvant to subcutaneous tumor vaccines that enhance long-term survival and generate protective tissue-resident memory CD4+ T-cells., Competing Interests: Authors ATC, MRC, MS, NT, CP, CS, JPV, CJB, and WCL are listed as inventors in an active U.S. patent (US10,610,583) entitled “Methods and compositions for treating glioma and medulloblastoma brain tumors using the zika virus” assigned to the Reagents of the University of Minnesota. This does not alter our adherence to PLOS ONE policies on sharing data and materials. All other authors disclose no competing interests.

Therapeutic drug monitoring is used in the clinical setting in the optimisation of dosages to overcome inter-patient pharmacokinetic variability, increasing efficacy whilst reducing toxicity. Imatinib is a tyrosine kinase inhibitor, displaying large variations in plasma concentrations that impact therapeutic success. As a result, imatinib has been the focus in the development of innovative techniques, aimed at its quantification in plasma. Liquid chromatography coupled with tandem mass spectrometry is currently the gold standard; however, cost and availability of the equipment limit its wider application in clinical settings. Recent advances in the field have shown Raman spectroscopy and electrochemistry to be key techniques for the development of promising analytical tools. This article reviews the latest advances towards less costly, more portable solutions that can be used at the point of care. Graphical abstract.

Influenza A and B viruses cause seasonal worldwide influenza epidemics each winter, and are a major public health concern and cause of morbidity and mortality. A substantial reduction in influenza-related deaths can be attributed to both vaccination and administration of oseltamivir (OS), which is approved for oral administration and inhibits viral neuraminidase (NA), a transmembrane protein. OS carboxylate (OSC), the active form of OS, is formed by the action of endogenous esterase, which targets NA and is shown to significantly reduce influenza-related deaths. However, the development of resistance in various viral variants, including H3N2 and H5N1, has raised concern about the effectiveness of OS. This comprehensive review covers a range of OS analogs shown to be effective against influenza virus, comparing different types of substituent group that contribute to the activity and bioavailability of these compounds., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In equine and racing practice, detomidine and butorphanol are commonly used in combination for their sedative properties. The aim of the study was to produce detection times to better inform European veterinary surgeons, so that both drugs can be used appropriately under regulatory rules. Three independent groups of 7, 8 and 6 horses, respectively, were given either a single intravenous administration of butorphanol (100 µg/kg), a single intravenous administration of detomidine (10 µg/kg) or a combination of both at 25 (butorphanol) and 10 (detomidine) µg/kg. Plasma and urine concentrations of butorphanol, detomidine and 3-hydroxydetomidine at predetermined time points were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The intravenous pharmacokinetics of butorphanol dosed individually compared with co-administration with detomidine had approximately a twofold larger clearance (646 ± 137 vs. 380 ± 86 ml hr -1  kg -1 ) but similar terminal half-life (5.21 ± 1.56 vs. 5.43 ± 0.44 hr). Pseudo-steady-state urine to plasma butorphanol concentration ratios were 730 and 560, respectively. The intravenous pharmacokinetics of detomidine dosed as a single administration compared with co-administration with butorphanol had similar clearance (3,278 ± 1,412 vs. 2,519 ± 630 ml hr -1  kg -1 ) but a slightly shorter terminal half-life (0.57 ± 0.06 vs. 0.70 ± 0.11 hr). Pseudo-steady-state urine to plasma detomidine concentration ratios are 4 and 8, respectively. The 3-hydroxy metabolite of detomidine was detected for at least 35 hr in urine from both the single and co-administrations. Detection times of 72 and 48 hr are recommended for the control of butorphanol and detomidine, respectively, in horseracing and equestrian competitions., (© 2020 John Wiley & Sons Ltd.)

Boldenone is an anabolic-androgenic steroid that is prohibited in equine sports. Urine from the uncastrated male horse contains boldenone that is thought to be of endogenous origin and thus a threshold ('cut-off') concentration has been adopted internationally for free and conjugated boldenone to help distinguish cases of doping from its natural production. The testis is likely to be a source of boldenone. Qualitative analysis was performed on extracts of equine testicular homogenates (n = 3 horses) incubated non-spiked and in the presence of its potential precursors using liquid chromatography tandem mass spectrometry (LC-MS/MS) and LC high resolution mass spectrometry (LC-HRMS). Samples were analysed both underivatised and derivatised to increase the certainty of identification. In addition to previously reported endogenous steroids, analysis of non-spiked testicular tissue samples demonstrated the presence of boldenone and boldienone at trace levels in the equine testis. Incubation of homogenates with deuterium or carbon isotope labelled testosterone and androstenedione resulted in the matching stable isotope analogues of boldenone and boldienone being formed. Additionally, deuterium and carbon labelled 2-hydroxyandrostenedione was detected, raising the possibility that this steroid is a biosynthetic intermediate. In conclusion, boldenone and boldienone are naturally present in the equine testis, with the biosynthesis of these steroids arising from the conversion of testosterone and androstenedione. However, additional work employing larger numbers of animals, further enzyme kinetic experiments and pure reference standards for 2-OH androstenedione isomers would be required to better characterize the pathways involved in these transformations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Microplastic particles (MPs) are widely distributed in seawater. Fibrous MPs (microfibres) are often reported as the most commonly encountered shape of particle. To estimate MP concentrations in seawater, samples are often collected using towed nets (generally 300-350-μm mesh) and may underestimate the amount of microfibres present, which may pass through the mesh due to their narrow width. We compared the potential microplastic particle (PMP) concentration estimates provided by two different seawater sampling methods conducted at three commercial shellfish farms and three unfarmed sites in Baynes Sound, British Columbia, Canada. The methods were: 10-L bucket samples sieved through 63-μm mesh in situ and subsequently filtered through an 8-μm polycarbonate membrane; and 1-L bulk samples collected in jars and subsequently filtered to 8 μm. The jar samples yielded PMP concentrations averaging approximately 8.5 times higher than the bucket samples per L of water (at the site level), largely driven by differences in the number of microfibres. There was no significant difference in PNP concentration between shellfish farms and unfarmed sites. An analysis of MP concentrations and mesh sizes reported in the literature suggests that using a 300-350-μm mesh may underestimate total MP concentrations by one to four orders of magnitude compared with samples that are filtered through much smaller mesh sizes (e.g. <100 μm), despite the effect of sample volume. Particles <300 μm in diameter make up a large component of MPs commonly found in fish and invertebrates. As such, common sampling practices fail to adequately measure a biologically relevant class of MPs, thereby undermining the ability to quantify ecological risk. We suggest that seawater sampling methods be designed to filter to <10 μm (the approximate width of many microfibres), either using pressurized pumps for large-volume samples, or by using sufficient replication of small-volume discrete samples., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Covalently crosslinked nanogels are widely explored as drug delivery systems and sensors. Radical polymerization provides a simple, inexpensive, and broadly applicable approach for their preparation, although the random nature of the reaction requires careful study of the final chemical composition. We demonstrate how the different reactivities of the monomers influence the total degree of incorporation into the polymer matrix and the role played by the experimental parameters in maximizing polymerization efficiency. Nanogels based on N -isopropylacrylamide, N - n -propylacrylamide, and acrylamide crosslinked with N,N' -methylenebisacrylamide were included in this study, in combination with functional monomers N -acryloyl-l-proline, 2-acrylamido-2-methyl-1-propanesulfonic acid, and 4-vinyl-1 H -imidazole. Total monomer concentration and initiator quantities are determining parameters for maximizing monomer conversions and chemical yields. The results show that the introduction of functional monomers, changes in the chemical structure of the polymerizable unit, and the addition of templating molecules can all have an effect on the polymerization kinetics. This can significantly impact the final composition of the matrices and their chemical structure, which in turn influence the morphology and properties of the nanogels.

Varicella zoster virus (VZV) is a highly prevalent human pathogen that causes varicella (chicken pox) during primary infection and establishes latency in peripheral neurons. Symptomatic reactivation often presents as zoster (shingles), but it has also been linked to life-threatening diseases such as encephalitis, vasculopathy and meningitis. Zoster may be followed by postherpetic neuralgia, neuropathic pain lasting after resolution of the rash. The mechanisms of varicella zoster virus (VZV) latency and reactivation are not well characterized. This is in part due to the human-specific nature of VZV that precludes the use of most animal and animal-derived neuronal models. Recently, in vitro models of VZV latency and reactivation using human neurons derived from stem cells have been established facilitating an understanding of the mechanisms leading to VZV latency and reactivation. From the models, c-Jun N-terminal kinase (JNK), phosphoinositide 3-kinase (PI3K) and nerve growth factor (NGF) have all been implicated as potential modulators of VZV latency/reactivation. Additionally, it was shown that the vaccine-strain of VZV is impaired for reactivation. These models may also aid in the generation of prophylactic and therapeutic strategies to treat VZV-associated pathologies. This review summarizes and analyzes the current human neuronal models used to study VZV latency and reactivation, and provides some strategies for their improvement.

Varicella zoster virus (VZV) is a neurotropic alphaherpesvirus that, following primary infection (varicella), establishes latency in sensory, autonomic, sympathetic and parasympathetic neurons, where it remains until reactivation (zoster). VZV-specific cell-mediated immune responses maintain VZV latency; thus, immunosuppressed and elderly persons are at risk of reactivation and associated neurological diseases. However, the cytokines produced by the immune system that control VZV in neurons are largely unknown. Therefore, to better understand how the immune system may restrict VZV in neurons, we studied interleukin-6, tumor necrosis factor-alpha and type 1 interferons for their ability to inhibit VZV replication in human neurons in vitro. Our studies revealed that VZV transcription and viral spread were significantly reduced by interleukin-6 and type 1 interferons, and to a lesser extent by tumor necrosis factor-alpha. These findings will help in understanding how the innate immune system limits virus replication in neurons in vivo., (Copyright © 2018 Elsevier Inc. All rights reserved.)

RAFT-synthesized polymers are typically colored and malodorous due to the presence of the sulfur-based RAFT end-group(s). In principle, RAFT end-groups can be removed by treating molecularly dissolved copolymer chains with excess free radical initiators, amines, or oxidants. Herein we report a convenient method for the removal of RAFT end-groups from aqueous dispersions of diblock copolymer nano-objects using H 2 O 2 . This oxidant is relatively cheap, has minimal impact on the copolymer morphology, and produces benign side products that can be readily removed via dialysis. We investigate the efficiency of end-group removal for various diblock copolymer nano-objects prepared with either dithiobenzoate- or trithiocarbonate-based RAFT chain transfer agents. The advantage of using UV GPC rather than UV spectroscopy is demonstrated for assessing both the kinetics and extent of end-group removal., Competing Interests: The authors declare no competing financial interest.

Background: Every day, patients are admitted to the hospital with conditions that could have been effectively managed in the primary care sector. These admissions are expensive and in many cases are possible to avoid if early intervention occurs. General practitioners are in the best position to identify those at risk of imminent hospital presentation and admission; however, it is not always possible for all the factors to be considered. A lack of shared information contributes significantly to the challenge of understanding a patient's full medical history. Some health care systems around the world use algorithms to analyze patient data in order to predict events such as emergency presentation; however, those responsible for the design and use of such systems readily admit that the algorithms can only be used to assess the populations used to design the algorithm in the first place. The United Kingdom health care system has contributed data toward algorithm development, which is possible through the unified health care system in place there. The lack of unified patient records in Australia has made building an algorithm for local use a significant challenge., Objective: Our objective is to use linked patient records to track patient flow through primary and secondary health care in order to develop a tool that can be applied in real time at the general practice level. This algorithm will allow the generation of reports for general practitioners that indicate the relative risk of patients presenting to an emergency department., Methods: A previously designed tool was used to deidentify the general practice and hospital records of approximately 100,000 patients. Records were pooled for patients who had attended emergency departments within the Eastern Health Network of hospitals and general practices within the Eastern Health Network catchment. The next phase will involve development of a model using a predictive analytic machine learning algorithm. The model will be developed iteratively, testing the combination of variables that will provide the best predictive model., Results: Records of approximately 97,000 patients who have attended both a general practice and an emergency department have been identified within the database. These records are currently being used to develop the predictive model., Conclusions: Records from general practice and emergency department visits have been identified and pooled for development of the algorithm. The next phase in the project will see validation and live testing of the algorithm in a practice setting. The algorithm will underpin a clinical decision support tool for general practitioners which will be tested for face validity in this initial study into its efficacy., Competing Interests: Conflicts of Interest: None declared., (©Christopher M Pearce, Adam McLeod, Jon Patrick, Douglas Boyle, Marianne Shearer, Paula Eustace, Mary Catherine Pearce. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 20.12.2016.)

Salbutamol sulphate (Ventolin Evohaler) was administrated via the inhalation route to six horses at a dose of 0.5 mg every 4 h during the day for 2 days (total dose 4 mg). Urine and blood samples were taken up to 92 h postadministration. Hydrolyzed plasma and urine were extracted using solid phase extraction (SPE). A sensitive tandem mass spectrometric method was developed in this study, achieving a lower limit of quantification (LLOQ) for salbutamol of 10 pg/mL in plasma and urine. The parent drug was identified using UPLC-MS/MS. Most of the determined salbutamol plasma concentrations, post last administration, lie below the LLOQ of the method and so cannot be used for plasma PK analysis. Urine PK analysis suggests a half-life consistent with the pharmacological effect duration. An estimate of the urine average concentration at steady-state was collected by averaging the concentration measurements in the dosing period from -12 to 0 h relative to the last administered dose. The value was averaged across the six horses and used to estimate an effective urine concentration as a marker of effective lung concentration. The value estimated was 9.6 ng/mL and from this a number of detection times were calculated using a range of safety factors., (© 2014 John Wiley & Sons Ltd.)

Background: Computerized medical records (CMR) are used in most Australian general practices. Although CMRs have the capacity to amalgamate and provide data to the clinician about their standard of care, there is little research on the way in which they may be used to support clinical governance: the process of ensuring quality and accountability that incorporates the obligation that patients are treated according to best evidence., Objective: The objective of this study was to explore the capability, capacity, and acceptability of CMRs to support clinical governance., Methods: We conducted a realist review of the role of seven CMR systems in implementing clinical governance, developing a four-level maturity model for the CMR. We took Australian primary care as the context, CMR to be the mechanism, and looked at outcomes for individual patients, localities, and for the population in terms of known evidence-based surrogates or true outcome measures., Results: The lack of standardization of CMRs makes national and international benchmarking challenging. The use of the CMR was largely at level two of our maturity model, indicating a relatively simple system in which most of the process takes place outside of the CMR, and which has little capacity to support benchmarking, practice comparisons, and population-level activities. Although national standards for coding and projects for record access are proposed, they are not operationalized., Conclusions: The current CMR systems can support clinical governance activities; however, unless the standardization and data quality issues are addressed, it will not be possible for current systems to work at higher levels.

Fluticasone propionate (FP) is an anti-inflammatory agent with topical and inhaled applications commonly used in the treatment of asthma in steroid-dependent individuals. The drug is used in racehorses to treat Inflammatory Airway Disease; this work was performed in order to advise on its use and detect potential misuse close to racing. Methods were developed for the extraction and analysis of FP from horse plasma and a carboxylic acid metabolite (FP-17βCOOH) from horse urine. The methods utilize ultra high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) in order to detect the extremely low concentrations of analyte present in both matrices. The developed methods were used to analyse plasma and urine samples collected following inhaled administration of FP to six thoroughbred horses. FP was detected in plasma for a minimum of 72 h post-administration and FP-17βCOOH was detected in urine for approximately 18 h post-administration. The results show that it is possible to detect FP in the horse following inhaled administration., (Copyright © 2012 John Wiley & Sons, Ltd.)

Population management of Lepeophtheirus salmonis in Canada currently relies on chemotherapeutants to remove attached stages of the ectoparasite. However, some populations of L. salmonis are developing resistance to chemotherapeutants making alternate management measures necessary. This article explores the ability of filter-feeding shellfish [i.e. blue mussels (Mytilus edulis) and Atlantic sea scallops (Placopecten magellanicus)] to consume the copepodid stages of L. salmonis in the laboratory under static and flowing water conditions, with variable copepodid densities, and with the aid of a light attractant. Mytilus edulis consumed copepodids under both static and flowing water conditions, and the proportion of individuals ingested was similar at low and high copepodid densities, suggesting that M. edulis was not saturated at the concentrations tested. Also, M. edulis consumed more copepodids when a light attractant was present, suggesting that lights may be useful to concentrate widely dispersed copepodids around cultured shellfish in the field. Finally, P. magellanicus consumed the same number of copepodids as an equivalent total wet weight of M. edulis. During each of the four separate experiments, shellfish consumed between 18 and 38% of the copepodids presented per hour, suggesting that both species are well suited for low level removal of copepodids over time., (© Her Majesty the Queen in Right of Canada 2013.)

National electronic health record initiatives are in progress in many countries around the world but the debate about the ethical issues and how they are to be addressed remains overshadowed by other issues. The discourse to which all others are answerable is a technical discourse, even where matters of privacy and consent are concerned. Yet a focus on technical issues and a failure to think about ethics are cited as factors in the failure of the UK health record system. In this paper, while the prime concern is the Australian Personally Controlled Electronic Health Record (PCEHR), the discussion is relevant to and informed by the international context. The authors draw attention to ethical and conceptual issues that have implications for the success or failure of electronic health records systems. Important ethical issues to consider as Australia moves towards a PCEHR system include: issues of equity that arise in the context of personal control, who benefits and who should pay, what are the legitimate uses of PCEHRs, and how we should implement privacy. The authors identify specific questions that need addressing.

We previously identified dissolved cadmium (Cd(diss)) as the main source of this metal in cultured Pacific oysters, Crassostrea gigas, in Deep Bay, British Columbia, Canada (Lekhi et al., 2008). Total suspended particulate Cd (Cd(part)) was not found to be a significant source of oyster Cd (Cd(oys)), with Cd(part) >20 μm negatively correlated with Cd(oys) concentration. High phytoplankton abundance in spring and summer was hypothesized to reduce Cd(oys) indirectly by drawing down Cd(diss) and increasing oyster growth. In the present study we expanded on these results by examining specifically how the phytoplankton community composition modulates both Cd(diss) and Cd(oys) concentrations in Deep Bay. Based on calculations of nutrients and Cd(diss) drawdown, phytoplankton accounted for approximately 90% of the overall summer reduction in Cd(diss) in the bay. Diatoms were the dominant phytoplankton group, being correlated negatively with Cd(oys) and positively with Cd(part). This suggests that diatom growth mediates the transfer of Cd from the dissolved to the particulate phase, resulting in lower Cd(oys). Spring blooms and sporadic harmful algal blooms may mediate a large flux of Cd(part) to the sediments. Thus, phytoplankton act as a sink, rather than a source, of Cd to oysters in Deep Bay and have a crucial role in the seasonality of Cd(oys) by reducing the concentration of Cd(diss) during the summer. Based on environmental variables, two descriptive models for annual Cd(oys) concentrations were developed using multiple linear regression. The first model (R(2)=0.870) was created to explain the maximum variability in Cd(oys) concentrations throughout the year, while the second (R(2)=0.806) was based on parameters that could be measured easily under farm conditions. Oyster age heavily affected both models, with the first model being secondarily affected by temperature and the second one being more sensitive to changes in salinity., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background: The study was undertaken to evaluate the contribution of a process which uses clinical trial data plus linked de-identified administrative health data to forecast potential risk of adverse events associated with the use of newly released drugs by older Australian patients., Methods: The study uses publicly available data from the clinical trials of a newly released drug to ascertain which patient age groups, gender, comorbidities and co-medications were excluded in the trials. It then uses linked de-identified hospital morbidity and medications dispensing data to investigate the comorbidities and co-medications of patients who suffer from the target morbidity of the new drug and who are the likely target population for the drug. The clinical trial information and the linked morbidity and medication data are compared to assess which patient groups could potentially be at risk of an adverse event associated with use of the new drug., Results: Applying the model in a retrospective real-world scenario identified that the majority of the sample group of Australian patients aged 65 years and over with the target morbidity of the newly released COX-2-selective NSAID rofecoxib also suffered from a major morbidity excluded in the trials of that drug, indicating a substantial potential risk of adverse events amongst those patients. This risk was borne out in post-release morbidity and mortality associated with use of that drug., Conclusions: Clinical trial data and linked administrative health data can together support a prospective assessment of patient groups who could be at risk of an adverse event if they are prescribed a newly released drug in the context of their age, gender, comorbidities and/or co-medications. Communication of this independent risk information to prescribers has the potential to reduce adverse events in the period after the release of the new drug, which is when the risk is greatest.Note: The terms 'adverse drug reaction' and 'adverse drug event' have come to be used interchangeably in the current literature. For consistency, the authors have chosen to use the wider term 'adverse drug event' (ADE).

Analysis of equine plasma samples to detect the abuse of anabolic steroids can be complicated when the parent steroid is endogenous to the animal. Anabolic steroids are usually administered intramuscularly as synthetic esters and therefore detection of the exogenous esters provides unequivocal proof of illegal administration. An ultra high performance liquid chromatography tandem mass spectrometric (UPLC-MSMS) method for the analysis of esters of testosterone (propionate, phenylpropionate, isocaproate, and decanoate) and boldenone (undecylenate) in equine plasma has been developed. Esters were extracted from equine plasma using a mixture of hexane and ethyl acetate and treated with methoxyamine hydrochloride to form methyloxime derivatives. Metenolone enanthate was used as an internal standard. After chromatographic separation, the derivatized steroid esters were quantified using selected reaction monitoring (SRM). The limit of detection for all of the steroid esters, based on a signal to noise ratio (S/N) of 3:1, was 1-3 pg/mL. The lower limit of quantification (LLOQ) for the all of the steroid esters was 5 pg/mL when 2 mL of plasma was extracted. Recovery of the steroid esters was 85-97% for all esters except for testosterone decanoate which was recovered at 62%. The intra-day coefficient of variation (CV) for the analysis of plasma quality control (QC) samples was less than 9.2% at 40 pg/mL and less than 6.0% at 400 pg/mL. The developed assay was used to successfully confirm the presence of intact testosterone esters in equine plasma samples following intramuscular injection of Durateston® (mixed testosterone esters)., (Copyright © 2011 John Wiley & Sons, Ltd.)

Objectives: To review the literature on different models of clinical governance and to explore their relevance to Australian primary health care, and their potential contributions on quality and safety., Data Sources: 25 electronic databases, scanning reference lists of articles and consultation with experts in the field. We searched publications in English after 1999, but a search of the German language literature for a specific model type was also undertaken. The grey literature was explored through a hand search of the medical trade press and websites of relevant national and international clearing houses and professional or industry bodies. 11 software packages commonly used in Australian general practice were reviewed for any potential contribution to clinical governance., Study Selection: 19 high-quality studies that assessed outcomes were included., Data Extraction: All abstracts were screened by one researcher, and 10% were screened by a second researcher to crosscheck screening quality. Studies were reviewed and coded by four reviewers, with all studies being rated using standard critical appraisal tools such as the Strengthening the Reporting of Observational Studies in Epidemiology checklist. Two researchers reviewed the Australian general practice software. Interviews were conducted with 16 informants representing service, regional primary health care, national and international perspectives., Data Synthesis: Most evidence supports governance models which use targeted, peer-led feedback on the clinician's own practice. Strategies most used in clinical governance models were audit, performance against indicators, and peer-led reflection on evidence or performance., Conclusions: The evidence base for clinical governance is fragmented, and focuses mainly on process rather than outcomes. Few publications address models that enhance safety, efficiency, sustainability and the economics of primary health care. Locally relevant clinical indicators, the use of computerised medical record systems, regional primary health care organisations that have the capacity to support the uptake of clinical governance at the practice level, and learning from the Aboriginal community-controlled sector will help integrate clinical governance into primary care.

Effective detection of the abuse of androgenic-anabolic steroids in human and animal sports often requires knowledge of the drug's metabolism in order to target appropriate urinary metabolites. 'Designer' steroids are problematic since it is difficult to obtain ethical approval for in vivo metabolism studies due to a lack of a toxicological profile. In this study, the in vitro metabolism of estra-4,9-diene-3,17-dione is reported for the first time. This is also the first study comparing the metabolism of a designer steroid in the three major species subject to sport's doping control; namely the equine, canine and human. In order to allow the retrospective analysis of sample testing data, the use of a high-resolution (HR) accurate-mass Thermo LTQ-Orbitrap LC-MS instrument was employed for metabolite identification of underivatised sample extracts. The full scan HR-LC-MS Orbitrap data was complimented by several further experiments targeted at elucidating more detailed structural information for the most abundant metabolites. These included; HR-LC-MS/MS of the underivatised metabolites, functional group selective chemical derivatisation followed by full scan HR-LC-MS, enzyme inhibition experiments and full scan electron ionization GC-MS analysis of methoxyamine-trimethylsilyl derivatives. The major metabolite detected in all species, and therefore the most suitable candidate for screening of estra-4,9-diene-3,17-dione abuse, was proposed to be an isomer of 17-hydroxy-estra-4,9-dien-3-one. Less significant metabolic pathways in all species included hydroxylation and reduction followed by hydroxylation. Reductive metabolism in the canine was less significant than in the other two species, while the equine was unique in producing a di-reduced metabolite (proposed to be an isomer of estra-4,9-diene-3,17-diol) and also relatively large quantities of d-ring hydroxy and hydroxy-reduced metabolites.

Pacific oysters (Crassostrea gigas) collected on the coast of British Columbia, Canada have occasionally shown cadmium (Cd) concentrations at or above 2 microg g(-1) (wet weight), which has resulted in the loss of some international markets. This study investigated the source and transfer of Cd to oysters by focusing on the role of dissolved and particulate Cd in seawater. Parameters monitored for 1 year at two oyster farm sites on Vancouver Island included: oyster tissue mass and shell length, Cd in oysters, dissolved Cd, particulate Cd, temperature and salinity. Results show that dissolved Cd was the main source of Cd to the oysters and that Cd was mainly concentrated in the gut tissues. A seasonal trend was observed in Cd in oysters, in which levels were lowest during periods of higher temperatures. Results also indicate that the local oceanographic inputs and sediment diagenesis directly affect dissolved Cd and thereby influence the Cd levels in oysters. Particulate matter was not found to be a source of Cd in oysters, and was actually negatively correlated. This was likely due to the uptake of dissolved Cd by phytoplankton and the effect of phytoplankton on oyster tissue mass.

Objective: To find out what supports effective links between Divisions of General Practice and universities., Design: Qualitative study based on semi-structured interviews during October 2004, from which a framework for effective linking was constructed and its validity assessed by discussion with researchers and Division staff and members at four interactive workshops held between 9 November 2004 and 5 November 2005 ., Participants: 21 participants from Divisions of General Practice and universities in Australia., Results: Qualities conceptualised as "opportunity" and "fair relationships" were critical factors in establishing successful links between the two sectors. The relationship between these two factors describes the types of interactions that currently occur., Conclusions: To develop effective links requires an environment that promotes adequate opportunities, and in which mutual trust can grow. This will require commitment and system change from all parties.

Objective: To examine doctors' perceptions and attitudes to prescribing within the Authority Prescribing System (APS)., Design and Setting: Questionnaire survey of Australian doctors' responses to a number of statements and factorial vignettes, conducted between 1 May and 30 June 2001., Participants: A national random sample of 1200 doctors, stratified according to specialist/generalist, rural/urban and high/low prescriber: 669 (56%) responded., Main Outcome Measures: Self-reported perceptions of the APS and attitudes to prescribing within the APS., Results: 72% of doctors agreed that the APS makes effective medications available to the socioeconomically disadvantaged members of the Australian public and 50% agreed that it compromises patient privacy. Fewer agreed that authority indicators were based on the highest quality of evidence quality (40%) or medication safety (12%). Doctors placed more emphasis on the doctor-patient relationship than on the criteria for authority prescribing in their decisions about prescribing APS medications. Doctors who used computers to prescribe were more likely to agree that computers can improve the authority prescribing process., Conclusions: This study suggests that authority-required prescribing is not achieving the stated aims of the National Medicines Policy in reducing variability in prescribing. Strategies to improve the quality of prescribing must consider the professional and ethical conundrum associated with prescribing outside of PBS/APS approved use for clinical and patient-centred reasons.

Russian olive (Elaeagnus angustifolia L.) was introduced in 1950 onto one site on the Milk River floodplain, northern Montana, 10 km downstream from the Canada/United States border. To analyze dispersal of Russian olive from the point source between 1950 and 1999, we compared distribution, numbers, size structure, and mortality of Russian olive and plains cottonwood (Populus deltoides Marsh:) on an unregulated reach of the Milk River floodplain in southeastern Alberta and north-central Montana. Within 50 years, Russian olive in this reach has moved upriver into Alberta and downriver to the Fresno Reservoir. It is now present on 69 of the 74 meander lobes sampled, comprising 34%, 62%, and 61% of all Russian olive and plains cottonwood seedlings, saplings, and trees, respectively. On some meander lobes, Russian olive has colonized similar elevations on the floodplain as plains cottonwood and is oriented in rows paralleling the river channel, suggesting that recruitment may be related to river processes. Breakup ice had killed 400 Russian olive saplings and trees and damaged >1000 others on 30 of the meander lobes in 1996. Nevertheless, Russian olive now outnumbers cottonwood on many sites on the Milk River floodplain because its seeds can be dispersed by wildlife (particularly birds) and probably by flood water and ice rafts; seeds are viable for up to 3 years and germination can take place on bare and well-vegetated soils; and saplings and trees are less palatable to livestock and beaver than plains cottonwood. Without control, Russian olive could be locally dominant on the Milk River floodplain in all age classes within 10 years and replace plains cottonwood within this century.