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Purpose: A novel phantom‐imaging platform, a set of software tools, for automated and high‐precision imaging of the American College of Radiology (ACR) positron emission tomography (PET) phantom for PET/magnetic resonance (PET/MR) and PET/computed tomography (PET/CT) systems is proposed. Methods: The key feature of this platform is the vector graphics design that facilitates the automated measurement of the knife‐edge response function and hence image resolution, using composite volume of interest templates in a 0.5 mm resolution grid applied to all inserts of the phantom. Furthermore, the proposed platform enables the generation of an accurate μ$\mu$‐map for PET/MR systems with a robust alignment based on two‐stage image registration using specifically designed PET templates. The proposed platform is based on the open‐source NiftyPET software package used to generate multiple list‐mode data bootstrap realizations and image reconstructions to determine the precision of the two‐stage registration and any image‐derived statistics. For all the analyses, iterative image reconstruction was employed with and without modeled shift‐invariant point spread function and with varying iterations of the ordered subsets expectation maximization (OSEM) algorithm. The impact of the activity outside the field of view (FOV) was assessed using two acquisitions of 30 min each, with and without the activity outside the FOV. Results: The utility of the platform has been demonstrated by providing a standard and an advanced phantom analysis including the estimation of spatial resolution using all cylindrical inserts. In the imaging planes close to the edge of the axial FOV, we observed deterioration in the quantitative accuracy, reduced resolution (FWHM increased by 1–2 mm), reduced contrast, and background uniformity due to the activity outside the FOV. Although it slows convergence, the PSF reconstruction had a positive impact on resolution and contrast recovery, but the degree of improvement depended on the regions. The uncertainty analysis based on bootstrap resampling of raw PET data indicated high precision of the two‐stage registration. Conclusions: We demonstrated that phantom imaging using the proposed methodology with the metric of spatial resolution and multiple bootstrap realizations may be helpful in more accurate evaluation of PET systems as well as in facilitating fine tuning for optimal imaging parameters in PET/MR and PET/CT clinical research studies. [ABSTRACT FROM AUTHOR]

Artificial carbon dioxide removal (CDR) from the atmosphere has been proposed as a measure for mitigating climate change and restoring the climate system to a target state after exceedance ("overshoot"). This research investigates to what extent overshoot and subsequent recovery of a given cumulative CO2 emissions level by CDR leaves a legacy in the marine environment using an Earth system model. We use RCP2.6 and its extension to year 2300 as the reference scenario and design a set of cumulative emissions and temperature overshoot scenarios based on other RCPs. Our results suggest that the overshoot and subsequent return to a reference cumulative emissions level would leave substantial impacts on the marine environment. Although the changes in sea surface temperature, pH, and dissolved oxygen are largely reversible, global mean values and spatial patterns of these variables differ significantly from those in the reference scenario when the reference cumulative emissions are attained. Plain Language Summary: Commitments by countries to reduce emissions of carbon dioxide (CO2) fall short of what is needed to limit global warming to below 2°C, a goal of the Paris Agreement, creating a risk that the 2°C limit may be exceeded. Restoring global temperature to a target level after exceedance ("overshoot") requires artificial carbon dioxide removal (CDR) from the atmosphere. Earlier studies showed that changes in surface air temperature can be reversed by CDR but climate variables that take longer to respond to changes in atmospheric CO2 are slower to reverse. In this research we investigate to what extent the impacts of overshoot on the marine environment can be reversed with CDR. We show that the ocean responds slowly to a decrease in atmospheric CO2 concentration by CDR, particularly for scenarios with large levels of overshoot. The overshoot results in substantial impacts on the marine environment for centuries with potentially detrimental effects for marine ecosystems. Key Points: Changes in sea surface temperature, pH, and dissolved oxygen concentration in overshoot scenarios are largely reversibleChanges in average ocean values of these variables are not reversible centuries after the overshoot is removedSpatial changes in these variables exhibit substantial differences between overshoot and nonovershoot scenarios in some regions [ABSTRACT FROM AUTHOR]

Background and Objective: Cigarette smoking is a major risk factor for periodontitis, and smoking perturbs neutrophil reactive oxygen species production. This study tested the hypothesis that cigarette smoke extract (CSE) and its components/metabolites nicotine, cotinine and thiocyanate (SCN‐), may influence neutrophil functions. Material and Methods: Chemotaxis was assessed in neutrophils pre‐treated with CSE using real‐time video microscopy. Neutrophil extracellular trap (NET) release in response to CSE, nicotine, cotinine, SCN‐ as well as to phorbol 12‐myristate‐13‐acetate and hypochlorous acid following pre‐treatment with CSE, nicotine, cotinine or SCN‐ was assessed using fluorescence‐based assays. The impact of CSE and SCN‐ treatment on neutrophil respiratory burst‐ and inflammation‐related gene expression (NFKBIE, DNAJB1, CXCL8, NCF1, NCF2, CYBB) was determined by real‐time polymerase chain reaction. Results: Both CSE and SCN‐ pre‐treatment inhibited phorbol 12‐myristate‐13‐acetate‐stimulated NET release. Additionally, SCN‐ inhibited hypochlorous acid‐stimulated NET formation, while SCN‐ alone stimulated NET release. Overall, neutrophils pre‐treated with CSE exhibited reduced speed, velocity and directionality relative to untreated neutrophils. Although CSE and SCN‐ promoted DNAJB1 expression, increased redox‐related gene expression was only detected in response to SCN‐. Conclusion: These results suggest that CSE can alter ex vivo neutrophil activation by mechanisms independent of SCN‐ and nicotine, and SCN‐ may contribute to the perturbed innate immune responses observed in smokers. [ABSTRACT FROM AUTHOR]

Summary: Background: Anthelmintic resistance combined with limited chemotherapeutic options has prompted a change in approaches to control of equine helminth infections. Targeted selective treatment strategies use diagnostics to reduce anthelmintic use by treating individuals with worm burdens or egg shedding levels above a set threshold. While faecal egg count analysis has limitations for informing tapeworm treatment, a commercially available saliva‐based diagnostic test accurately diagnoses horses with tapeworm infection. Objectives: Evaluation of a saliva‐based diagnostic test to identify horses naturally infected with tapeworm and assess the impact of using the test to inform anthelmintic administration. Study design: Retrospective longitudinal study. Methods: Saliva was collected from horses (n = 237) at a UK welfare charity from autumn 2015 to autumn 2016. Horses diagnosed as positive for tapeworm infection using the EquiSal® Tapeworm test were anthelmintic treated according to weight. The number of horses that received anthelmintic treatment based on the test result was compared with an all‐group treatment approach and the reduction in anthelmintic usage calculated. Incoming horses were also tested (n = 143) and the information was used to inform quarantine treatments. Results: In autumn 2015, 85% of 237 horses tested received no anthelmintic and the majority (71%) of these remained below the treatment threshold throughout the study. Of the 69 horses that received treatment, seven required treatment following three subsequent tests, while >50% of horses administered with anthelmintic fell below the treatment threshold at the following test. No increase in tapeworm prevalence within the 237 horses was observed during the study despite a substantial reduction in the application of antitapeworm treatments. A total of 41% of incoming horses required anticestode treatment. Main limitations: Other management practices were not included in the analysis. Conclusions: Compared with an all‐group treatment strategy, the diagnostic‐led approach used here considerably reduced application of anticestode anthelmintics. This could reduce selection pressure for anthelmintic resistance. [ABSTRACT FROM AUTHOR]

Stepped wedge designs (SWDs) have received considerable attention recently, as they are potentially a useful way to assess new treatments in areas such as health services implementation. Because allocation is usually by cluster, SWDs are often viewed as a form of cluster-randomized trial. However, since the treatment within a cluster changes during the course of the study, they can also be viewed as a form of crossover design. This article explores SWDs from the perspective of crossover trials and designed experiments more generally. We show that the treatment effect estimator in a linear mixed effects model can be decomposed into a weighted mean of the estimators obtained from (1) regarding an SWD as a conventional row-column design and (2) a so-called vertical analysis, which is a row-column design with row effects omitted. This provides a precise representation of "horizontal" and "vertical" comparisons, respectively, which to date have appeared without formal description in the literature. This decomposition displays a sometimes surprising way the analysis corrects for the partial confounding between time and treatment effects. The approach also permits the quantification of the loss of efficiency caused by mis-specifying the correlation parameter in the mixed-effects model. Optimal extensions of the vertical analysis are obtained, and these are shown to be highly inefficient for values of the within-cluster dependence that are likely to be encountered in practice. Some recently described extensions to the classic SWD incorporating multiple treatments are also compared using the experimental design framework. [ABSTRACT FROM AUTHOR]

The article talks about the mock before you block approach for wrong-side anesthetic nerve block prevention. Topics discussed include information on the World Health Organization (WHO) surgical safety checklist, an importance of methods testing in simulation and suggestion related to injecting syringe label.

The global increase in anthelmintic resistant nematodes of ruminants, together with consumer concerns about chemicals in food, necessitates the development of alternative methods of control for these pathogens. Subunit recombinant vaccines are ideally placed to fill this gap. Indeed, they are probably the only valid option for the long-term control of ruminant parasitic nematodes given the increasing ubiquity of multidrug resistance in a range of worm species across the world. The development of a subunit multicellular parasite vaccine to the point of practical application would be a groundbreaking step in the control of these important endemic infections of livestock. This review summarizes the current status of subunit vaccine development for a number of important gastrointestinal nematodes of cattle and sheep, with a focus on the limitations and problems encountered thus far, and suggestions as to how these hurdles might be overcome. [ABSTRACT FROM AUTHOR]

Using cluster analyses, this study explored the relations among racial identity, perceived discrimination, and psychological concerns among 189 Caribbean Black American and African American adolescents. Findings showed that for all participants, less mature racial identity profiles were significantly related to perceived discrimination and psychological concerns. However, nuances in racial identity profiles between Caribbean Black American and African American participants suggest subtle ethnic group differences in racial identity development. Implications for practitioners and research are discussed. Usando análisis cluster, este estudio exploró las relaciones entre identidad racial, discriminación percibida y preocupaciones psicológicas en 189 adolescentes afroamericanos y americanos negros caribeños. Los hallazgos mostraron que, para todos los participantes, los perfiles de identidad racial menos maduros estaban significativamente relacionados con una discriminación percibida y preocupaciones psicológicas. Sin embargo, los matices de los perfiles de identidad racial entre los participantes afroamericanos y americanos negros caribeños sugieren unas diferencias sutiles entre ambos grupos étnicos en el desarrollo de la identidad racial. Se discuten las implicaciones para practicantes e investigadores. [ABSTRACT FROM AUTHOR]

Background The clinical utility of serum periostin as a type 2 biomarker in asthma is limited by lack of reference range values derived from a population without respiratory disease. Objective To derive age- and sex-related reference intervals for serum periostin from an adult population without asthma or COPD. Methods Serum periostin levels were measured in 480 individuals, comprising 60 female and 60 male adults in each of the 18- to 30-year, 31- to 45-year, 46- to 60-year and 61- to 75-year age groups. Key exclusion criteria included a doctor's diagnosis of asthma, chronic bronchitis or COPD, and a history of wheezing or use of respiratory inhalers in the last 12 months. The distribution of periostin and logarithm-transformed periostin levels was derived, and 90% confidence intervals for an individual prediction were calculated. Results The distribution of serum periostin was right skewed with a mean ( SD) periostin of 51.2 (11.9) ng/mL, median ( IQR) 50.1 (43.1 to 56.9) ng/mL and range 28.1 to 136.4 ng/mL. There was no association between logarithm periostin and age or sex, although levels were low in current smokers. The 90% confidence limits for periostin were 35.0 and 71.1 ng/mL. Conclusions and Clinical Relevance Serum periostin levels in adults without asthma or COPD are similar to those in adults with asthma. Serum periostin measurements do not need to be adjusted to take account of a patient's age or sex, although levels are lower in current smokers. Reference values for serum periostin levels in adults without asthma or COPD are provided. [ABSTRACT FROM AUTHOR]

Objective To better understand mental health service users' experiences of stigma and discrimination in different settings. Method An annual telephone survey of people with a mental health diagnosis conducted to evaluate the Time to Change antistigma campaign in England. Of 985 people who participated in 2013, 84 took part in a qualitative interview which was audio recorded. Of these, 50 interviews were transcribed and thematically analysed to explore accounts of discrimination. We analysed common types of behaviour; motivations ascribed to the discriminators; expectations of what fair treatment would have been; and the impact of discrimination on participants. Results Discrimination was most common in five contexts: welfare benefits, mental health care, physical health care, family and friends. Participants often found it hard to assess whether a behaviour was discriminatory or not. Lack of support, whether by public services or by friends and family, was often experienced as discrimination, reflecting an expectation that positive behaviours and reasonable adjustments should be offered in response to mental health needs. Conclusion The impact of discrimination across different settings was often perceived by participants as aggravating their mental health, and there is thus a need to treat discrimination as a health issue, not just a social justice issue. [ABSTRACT FROM AUTHOR]

SUMMARY Background Late graft failure after allogeneic haematopoietic cell transplantation ( HCT) can result from the failed engraftment of long-term engrafting cells. The use of thrombopoietin ( TPO) receptor agonists ( TRA) has been extensively studied and remains an important component of experimental ex vivo stem cell expansion protocols, but its use in allogeneic transplantation is still evolving. Methods We describe the use of eltrombopag, a TRA, to stimulate the rescue of late graft failure in a patient following allogeneic HCT, and we performed a systematic review of published studies describing the use of TRAs following allogeneic transplantation. Results A total of eight publications were identified from our systematic search and included observational case studies (five studies, total of seven patients) that primarily addressed ITP or isolated thrombocytopenia at various time points after allogeneic HCT and prospective clinical trials (three studies, total of 177 patients with 95 patients receiving TRAs). No studies reported specifically on the use of TRAs for the treatment of trilineage graft failure as a means of in vivo stem cell expansion. The use of TRAs following allogeneic HCT appears safe and promising. Conclusion The use of eltrombopag or other TRAs to treat poor graft function after allogeneic HCT is intriguing and warrants further study. [ABSTRACT FROM AUTHOR]

Background and Aim. The optimum management of Bowen’s Disease (BD) is undefined. A review of current practice is required to allow the development of best practice guidelines. Methods. All BD cases, diagnosed in one UK centre and one Australian centre over a year (1 July 2012–30 June 2013), were analysed retrospectively. Patients with BD were identified from histopathology reports and their medical records were analysed to collect demographic data, site of lesion, and treatment used. Results. The treatment of 155 lesions from the UK centre and 151 lesions from the Australian centre was analysed. At both centres BD was most frequently observed on the face: UK had 70 (45%) lesions and Australia had 83 (55%) lesions (P=0.08). The greatest number of lesions was managed by the plastic surgery department in the UK centre, 72 (46%), and the dermatology department in the Australian centre, 121 (80%). The most common therapy was surgical excision at both centres. Conclusions. In both UK and Australia, BD arises on sun-exposed sites and was most commonly treated with surgical excision despite a lack of robust evidence-based guidelines. [ABSTRACT FROM AUTHOR]

When the difference between treatments in a clinical trial is estimated by a difference in means, then it is well known that randomization ensures unbiassed estimation, even if no account is taken of important baseline covariates. However, when the treatment effect is assessed by other summaries, for example by an odds ratio if the outcome is binary, then bias can arise if some covariates are omitted, regardless of the use of randomization for treatment allocation or the size of the trial. We present accurate closed-form approximations for this asymptotic bias when important normally distributed covariates are omitted from a logistic regression. We compare this approximation with ones in the literature and derive more convenient forms for some of these existing results. The expressions give insight into the form of the bias, which simulations show is usable for distributions other than the normal. The key result applies even when there are additional binary covariates in the model. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background Raising a child with a disability places considerable demands and stress on parents, which can contribute to mental health difficulties. Research has primarily focused on mothers' mental health, and our understanding of the effects on fathers remains limited. The factors that place fathers at increased risk of mental health difficulties are also poorly understood. This study aimed to redress these gaps by reporting on the mental health of a large sample of fathers of children with an intellectual disability ( ID) (aged 3-15 years), comparing this to published Australian norms and mothers of children with ID. The second aim of the study was to explore risk factors associated with fathers' mental health. Method The data for this study come from 315 Australian fathers of children (aged 3-15 years) with ID, who participated in the large-scale evaluation of the Signposts for building better behaviour programme. Fathers completed a range of self-report questionnaires at baseline including the Depression Anxiety Stress Scale ( DASS). Results Fathers in the present sample reported significantly more symptoms of depression and stress than the Australian normative data, with approximately 6-8% reporting symptoms in the severe to extremely severe range. The strongest predictors of fathers' mental health difficulties were children's behaviour problems, daily stress arising from fathers' own needs and children's care needs, and low parenting satisfaction. Socio-economic factors did not predict mental health difficulties. Conclusion This study is among one of the first to report the mental health of fathers of children with a disability in Australia. Findings highlight that some fathers of children with ID are at heightened risk of experiencing mental health difficulties, underscoring the importance of the provision of information and interventions to promote their mental health. [ABSTRACT FROM AUTHOR]

Aim To determine if the glucagon-like peptide-1 ( GLP-1) receptor agonist albiglutide, once weekly, impairs counter-regulatory responses during hypoglycaemia. Methods We conducted a randomized, double-blind, parallel, placebo-controlled study in subjects with type 2 diabetes mellitus. A single dose of albiglutide 50 mg (n = 22) or placebo (n = 22) was administered on day 1. Glucose was clamped on day 4 (to coincide with the approximate albiglutide maximum plasma concentration) at 9.0, 5.0, 4.0, 3.3 and 2.8 mmol/l (162, 90, 72, 59.4 and 50.4 mg/dl), with a post-clamp recovery period to 3.9 mmol/l (70 mg/dl). Hormone measurements were made at each plateau and adverse events (AEs) were recorded. Results The counter-regulatory hormones glucagon, epinephrine, norepinephrine, growth hormone and cortisol were appropriately suppressed when plasma glucose levels were >4.0 mmol/l (>72 mg/dl), but increased in the albiglutide and placebo groups with glucose levels <3.3 mmol/l (<59.4 mg/dl) in response to hypoglycaemia. The area under the curve geometric mean ratios (albiglutide : placebo), calculated from the clamped plateau of 4.0 mmol/l (72 mg/dl) to the glucose recovery point, were not significantly different for any of the counter-regulatory hormones. When plasma glucose levels were >5.0 mmol/l (>90 mg/dl), albiglutide increased pancreatic β-cell secretion of C-peptide in a glucose-dependent manner to a greater extent than did placebo, and it was suppressed in each group when levels were <4.0 mmol/l (<72 mg/dl). No significant difference between groups was observed in the recovery time to glucose level ≥3.9 mmol/l (≥70 mg/dl). There were no clinically relevant differences in AEs or other safety variables. Conclusions A single 50-mg dose of albiglutide was well tolerated and did not impair the counter-regulatory response to hypoglycaemia. These data provide mechanistic evidence supporting the low intrinsic hypoglycaemic potential of albiglutide. [ABSTRACT FROM AUTHOR]

Equine gastrointestinal nematodes are ubiquitous; in horses that graze contaminated pasture and that are not treated appropriately, large numbers of worms can accumulate, which can lead to serious clinical disease. Nematode control has traditionally followed interval treatment regimens, which involve regular anthelmintic administration to all horses based on the strongyle egg reappearance periods of each drug, usually defined around the time of licensing. Interval treatment programmes have resulted in substantial reductions in large strongyle disease, but have made major contributions to the development of anthelmintic resistance, particularly in cyathostomins. Cyathostomin resistance to 2 of the 3 available anthelmintic classes is widespread, and resistance to both classes in single populations is not uncommon. Reduced efficacy of the most commonly used macrocyclic lactone anthelmintics, as measured by shortened egg reappearance periods after treatment, is emerging in cyathostomins. Macrocyclic lactone resistance is also now commonly reported in Parascaris equorum on stud farms. Faecal worm egg counts ( FWEC) are increasingly being used as part of targeted approaches to parasite control, whereby only those horses with moderate to high FWEC within a group are treated with an anthelmintic. The objective of this approach is to reduce environmental contamination, while leaving a proportion of the worm population in some horses unexposed to selection pressure for anthelmintic resistance. This article reviews recent findings in equine parasitology research that will underpin guidelines for control, with a particular focus on how to optimise the value of FWEC methodologies and anthelmintic efficacy analyses. [ABSTRACT FROM AUTHOR]

Background Interleukin 13 ( IL13) is a T-helper type 2 (Th2) cytokine associated with inflammation and pathology in allergic diseases such as bronchial asthma. We have shown that treatment with lebrikizumab, an anti- IL13 monoclonal antibody, significantly improves prebronchodilator forced expiratory volume in 1 s ( FEV1) in a subset of subjects with uncontrolled asthma. Objective To evaluate efficacy and safety of lebrikizumab in subjects with mild asthma who underwent bronchial allergen challenge. Methods Twenty-nine subjects were randomized 1 : 1-5 mg/kg lebrikizumab ( n = 13) or placebo ( n = 16) administered subcutaneously every 4 weeks over 12 weeks, a total of four doses. Primary efficacy outcome was late asthmatic response (LAR) at Week 13, defined as area under the curve of FEV1 measured 2-8 h following inhaled allergen challenge. Serum biomarkers were measured to verify IL13 pathway inhibition and identify patients with an increased response to lebrikizumab. Results At Week 13, the LAR in lebrikizumab subjects was reduced by 48% compared with placebo subjects, although this was not statistically significant (95% confidence interval, −19%, 90%). Exploratory analysis indicated that lebrikizumab-treated subjects with elevated baseline levels of peripheral blood eosinophils, serum IgE, or periostin exhibited a greater reduction in LAR compared with subjects with lower baseline levels of these biomarkers. Lebrikizumab exerted systemic effects on markers of Th2 inflammation, reducing serum immunoglobulin E (IgE), chemokine ligands 13 and 17 by approximately 25% ( P < 0.01). Lebrikizumab was well tolerated. Conclusion and Clinical Relevance Lebrikizumab reduced the LAR in subjects with mild asthma. Clinical trial number NCT00781443. [ABSTRACT FROM AUTHOR]

Background The OX40/ OX40L interaction contributes to an optimal T cell response following allergic stimuli and plays an important role in the maintenance and reactivation of memory T effector cells. Objective We tested whether treatment with an anti- OX40L monoclonal antibody ( MAb) would inhibit allergen-induced responses in subjects with asthma. Methods Twenty-eight mild, atopic asthmatic subjects were recruited for a double-blind, randomized, placebo-controlled, parallel-group trial (ClinicalTrials.gov identifier NCT00983658) to compare blockade of OX40L using a humanized anti- OX40L MAb to placebo-administered intravenously in 4 doses over 3 months. Allergen inhalation challenges were carried out 56 and 113 days after the first dose of study drug. The primary outcome variable was the late-phase asthmatic response. Other outcomes included the early-phase asthmatic response, airway hyperresponsiveness, serum IgE levels, blood and sputum eosinophils, safety and tolerability. Results Treatment with anti- OX40L MAb did not attenuate the early- or late-phase asthmatic responses at days 56 or 113 compared with placebo. In the anti- OX40L MAb treatment group, total IgE was reduced 17% from pre-dosing levels, and sputum eosinophils decreased 75% by day 113 (both P = 0.04). There was no effect of anti- OX40L MAb on airway hyperresponsiveness or blood eosinophils. The frequency of AEs was similar in both groups. Conclusion and Clinical Relevance Pharmacological activity of anti- OX40L MAb was observed by decreases in serum total IgE and airway eosinophils at 16 weeks post-dosing, but there was no effect on allergen-induced airway responses. It is possible that the treatment duration or dose of antibody was insufficient to impact the airway responses. [ABSTRACT FROM AUTHOR]

Reasons for performing study Anthelmintic resistance in equine gastrointestinal nematodes is a threat to equine health and welfare. Detailed knowledge of anthelmintic use and parasite control methods is a prerequisite to identification of potential risk factors for resistance. Objectives To identify parasite control practices employed by equine owners in Scotland and investigate management factors associated with anthelmintic resistance. Study design Questionnaire study of equine parasite control in Scotland. Methods Questionnaires were available electronically, distributed at a conference and mailed to clients. Key areas explored included general background, grazing management, anthelmintic treatment practices and use of diagnostic tests. Results A total of 193 responses detailing information on parasite control programmes of 993 equids were analysed. Moxidectin ( MOX) and ivermectin or related combination products were the most commonly administered anthelmintics in the preceding 12 months. Treatments licensed for use against cyathostomin encysted larvae and tapeworms were administered by 80% and 90% of respondents, respectively. This was often achieved through indiscriminate use of MOX and MOX-praziquantel products. Faecal egg count ( FEC) analysis had been performed on 62% of yards and regular use of FECs reduced annual anthelmintic treatment frequency. Veterinarians had the greatest influence on control practices. While 40% of respondents believed that they practised targeted dosing, this was not associated with delaying treatment beyond the egg reappearance period of the anthelmintic used. Conclusions Responses indicated increasing veterinary involvement and use of FECs. The majority of respondents administered anthelmintics licensed against cyathostomin encysted larvae and tapeworms. However, responses suggested that owners did not understand the definition of 'targeted' dosing regimens. Potential relevance The high frequency of MOX use represents a potential risk factor for macrocyclic lactone resistance. As veterinarians were the most influential factor in anthelmintic choice, awareness of macrocyclic lactone resistance and potential risk factors for its development and spread should be incorporated into client advice. [ABSTRACT FROM AUTHOR]

Reasons for performing study Cyathostomins comprise 50 helminth species, considered the most problematic equine endoparasites. Three classes of anthelmintic are currently licensed for their control, namely the benzimidazoles (fenbendazole), tetrahydropyrimidines (pyrantel) and macrocyclic lactones (ivermectin and moxidectin). Anthelmintic resistance in cyathostomins is common. With no new classes expected in the near future, it is essential to determine the efficacy of the available anthelmintics to inform future control programmes. Objectives To determine the efficacy of all 3 anthelmintic classes against strongyles in equids on livery yards in east and central Scotland. Study design Anthelmintic efficacy testing using the faecal egg count reduction test (FECRT). Methods FECRTs were performed on equids with initial strongyle faecal egg counts ( FECs) of ≥50 eggs per gram. Efficacy was determined by comparing pretreatment (Day 0) and 14 days post treatment (Day 14) FECs. The following chemicals were tested: fenbendazole, pyrantel, ivermectin and moxidectin. Group arithmetic mean FECR of >90% for fenbendazole and pyrantel, and >95% for ivermectin and moxidectin, represented efficacy, whereas lower mean FECR indicated potential resistance. Results A total of 447 FECRTs were performed on 15 yards, as follows (the numbers in parentheses represent the number of yards each anthelmintic was tested on): 55 equids (7 yards) fenbendazole, 111 (8 yards) pyrantel, 163 (13 yards) ivermectin and 118 (10 yards) moxidectin. Fenbendazole resistance was documented on all yards (range of mean FECR, 15.8-83.4%), whereas pyrantel (90.4-99.6%), ivermectin (99.5-100%) and moxidectin (99.4-100%) treatment had acceptable efficacy. Conclusions Reduced efficacy of fenbendazole was widespread, whereas >90% efficacy was found after pyrantel, and >95% efficacy after ivermectin and moxidectin. Overall, efficacies were higher than reported previously in Europe and the USA, potentially reflecting differences in management and anthelmintic use on the yards surveyed. Potential relevance The use of fenbendazole for strongyle control in Scotland should be questioned. Targeted use of pyrantel should be encouraged to reduce reliance on macrocyclic lactones. Further work to correlate management practices with the presence of anthelmintic resistance is warranted. The Summary is available in Chinese - see Supporting information. [ABSTRACT FROM AUTHOR]

The article presents a cost comparison between the interval programme treatment and faecal egg count (FEC) directed anthelmintic delivery in horses. The study analyzed data from 368 horses owned by those who participated in an anthelmintic treatment initiative in 2012. It says that the horses were treated with various regimes such as praziquantel (PRZ), cyathostomin larvicidal treatment. Results show that the use of FEC could reduce financial costs compared with the interval treatment regimens.

Roundworms and flatworms that affect donkeys can cause disease. All common helminth parasites that affect horses also infect donkeys, so animals that co-graze can act as a source of infection for either species. Of the gastrointestinal nematodes, those belonging to the cyathostomin (small strongyle) group are the most problematic in UK donkeys. Most grazing animals are exposed to these parasites and some animals will be infected all of their lives. Control is threatened by anthelmintic resistance: resistance to all 3 available anthelmintic classes has now been recorded in UK donkeys. The lungworm, Dictyocaulus arnfieldi, is also problematical, particularly when donkeys co-graze with horses. Mature horses are not permissive hosts to the full life cycle of this parasite, but develop clinical signs on infection. In contrast, donkeys are permissive hosts without displaying overt clinical signs and act as a source of infection to co-grazing horses. Donkeys are also susceptible to the fluke, Fasciola hepatica. This flatworm can be transmitted, via snails and the environment, from ruminants. As with cyathostomins, anthelmintic resistance is increasing in fluke populations in the UK. A number of the anthelmintic products available for horses do not have a licence for use in donkeys, and this complicates the design of parasite control programmes. As no new equine anthelmintic classes appear to be near market, it is important that the efficacy of currently effective drugs is maintained. It is important that strategies are used that attempt to preserve anthelmintic efficacy. These strategies should be based on the concept that the proportion of worms in a population not exposed to anthelmintic at each treatment act as a source of 'refugia'. The latter is an important factor in the rate at which resistance develops. Thus, it is imperative that parasite control programmes take into account the need to balance therapy to control helminth-associated disease with the requirement to preserve anthelmintic effectiveness. [ABSTRACT FROM AUTHOR]

Background and Purpose Glucocorticoids are highly effective therapies for a range of inflammatory diseases. Advances in the understanding of the diverse molecular mechanisms underpinning glucocorticoid action suggest that anti-inflammatory molecules with reduced side effect liabilities can be discovered. Here we set out to explore whether modification of the 17α position of the steroid nucleus could generate molecules with a unique pharmacological profile and to determine whether such molecules would retain anti-inflammatory activity. Experimental Approach The pharmacological properties of GW870086 were compared with fluticasone propionate ( FP) using a range of cellular and in vivo model systems, including extensive gene expression profiling. Key Results GW870086 repressed inflammatory cytokine release from lung epithelial cells in a similar manner to FP but antagonized the effect of dexamethasone on MMTV-driven reporter gene transactivation. GW870086 had a strong effect on the expression of some glucocorticoid-regulated genes (such as PTGS2), while having minimal impact on the expression of other known target genes (such as SGK). GW870086 retained the ability to strengthen tight junctions in epithelial cell culture but, unlike FP, was unable to protect the culture from elastase-mediated damage. In murine models of irritant-induced contact dermatitis and ovalbumin-induced allergic inflammation, GW870086 showed comparable anti-inflammatory efficacy to FP. Conclusion and Implications GW870086 is a potent anti-inflammatory compound with a unique ability to regulate only a subset of those genes that are normally affected by classical glucocorticoids. It has the potential to become a new topical steroid with a different safety profile to existing therapies. [ABSTRACT FROM AUTHOR]

Decision-makers charged with implementing ecosystem-based management (EBM) rely on scientists to predict the consequences of decisions relating to multiple, potentially conflicting, objectives. Such predictions are inherently uncertain, and this can be a barrier to decision-making. The Convention on the Conservation of Antarctic Marine Living Resources requires managers of Southern Ocean fisheries to sustain the productivity of target stocks, the health and resilience of the ecosystem, and the performance of the fisheries themselves. The managers of the Antarctic krill fishery in the Scotia Sea and southern Drake Passage have requested advice on candidate management measures consisting of a regional catch limit and options for subdividing this among smaller areas. We developed a spatially resolved model that simulates krill-predator-fishery interactions and reproduces a plausible representation of past dynamics. We worked with experts and stakeholders to identify (1) key uncertainties affecting our ability to predict ecosystem state; (2) illustrative reference points that represent the management objectives; and (3) a clear and simple way of conveying our results to decision-makers. We developed four scenarios that bracket the key uncertainties and evaluated candidate management measures in each of these scenarios using multiple stochastic simulations. The model emphasizes uncertainty and simulates multiple ecosystem components relating to diverse objectives. We summarize the potentially complex results as estimates of the risk that each illustrative objective will not be achieved (i.e., of the state being outside the range specified by the reference point). This approach allows direct comparisons between objectives. It also demonstrates that a candid appraisal of uncertainty, in the form of risk estimates, can be an aid, rather than a barrier, to understanding and using ecosystem model predictions. Management measures that reduce coastal fishing, relative to oceanic fishing, apparently reduce risks to both the fishery and the ecosystem. However, alternative reference points could alter the perceived risks, so further stakeholder involvement is needed to identify risk metrics that appropriately represent their objectives. [ABSTRACT FROM AUTHOR]

Reasons for performing study: Improved education of veterinarians and equine owners/managers is essential in implementing parasite control strategies that are less reliant on chemicals. Methods: This questionnaire study, conducted on 61 UK Thoroughbred (TB) establishments during 2009 and 2010, was designed to obtain an understanding of current helminth control practices on studs. To our knowledge, this is the first occasion that statements obtained from TB studs via questionnaire have been supported by statistical analysis. Results: Despite many respondents indicating high levels of concern regarding anthelmintic resistance, 56% of these establishments that received visiting equines co-grazed these animals with permanent stock and <74% administered anthelmintics prior to integration. In the 12 months preceding the study, most respondents administered frequent macrocyclic lactone (ML) treatments, with none appearing to leave any animals in groups untreated at each administration. Indiscriminate whole group treatments with MLs and movement of animals to 'clean grazing' post treatment (reported by >25% of respondents), indicates that many stud owners/managers are not aware of the strong risk factors for the development of anthelmintic resistance. Few studs had conducted faecal egg count (FEC) analysis in the past and only 22% indicated that they considered this form of analysis beneficial in determining anthelmintic choice. Conclusions and potential relevance: The challenge now is to convince stud owners/managers to deviate from their current practices to control strategies that are more likely to preserve anthelmintic efficacy. Veterinarians need to get more involved in implementing these control strategies, with better emphasis placed on the role of diagnostic tests in facilitating targeted treatments and in investigating anthelmintic sensitivity in the associated nematode populations. [ABSTRACT FROM AUTHOR]

Summary Infections with parasitic nematodes are of significant welfare and economic importance worldwide, and because of the emergence of anthelmintic resistance, this has lead to alternative methods of parasite control being required. Vaccination offers a feasible alternative control, and the majority of research has focused on the production of recombinant versions of native antigens previously identified as protective in vaccinated animals. Attempts at the production of protective recombinant subunit vaccines have been hindered, however, as these antigens have invariably failed to replicate the same level of protective immune response as seen with the native versions. It has been proposed that these failures are owing to the fact that the recombinant proteins do not contain the appropriate post-translational modifications to retain the protective capacity of the native molecules. In this review, we discuss a novel approach to vaccine antigen identification through the application of random peptide phage-display libraries and their use to identify peptide sequences that potentially mimic the structure(s) of antigenic epitopes. This area of research is still relatively novel with respect to parasites, and the current state of the art will be discussed here. [ABSTRACT FROM AUTHOR]

A 12-month study was conducted to assess and monitor gastrointestinal tract nematodes and liver fluke in cohorts of cattle on a Scottish organic dairy farm. Various diagnostic markers for helminth parasites of cattle from different age groups were assessed monthly from April 2007 to March 2008. First season grazing stock were subjected to significant challenge from Ostertagia ostertagi nematodes as reflected in serum pepsinogen concentrations, which rose markedly in the second half of the grazing season. In addition, plasma albumin concentrations decreased and faecal egg counts (FEC) increased moderately, indicating exposure to both O ostertagi and probably Cooperia oncophora. Second season grazing animals had a peak FEC early in the grazing period, suggestive of a potential carry-over of Ostertagia species infection ('Type 2') during housing. All classes of cattle showed evidence of fluke (Fasciola hepatica) infection. Adult cow exposure to O ostertagi and fluke was estimated via the use of ELISA testing to detect antibodies to O ostertagi and F hepatica and the high levels detected suggested a significant exposure response. Despite low stocking densities and sympathetic grazing management, there was a significant challenge to all grazing stock from gastrointestinal nematodes and liver fluke. [ABSTRACT FROM AUTHOR]

Summary Cyathostomins represent a potential cause of equine morbidity and have become the main focus of endoparasite control in managed horses. All grazing horses are at risk of infection with cyathostomins; therefore, the application of appropriate management measures is essential. Anthelmintics currently comprise the main method of control for equine nematodes and the ready availability of these products in some countries has resulted in their use becoming dissociated from veterinary involvement. This is concerning given the levels of anthelmintic resistance that have been recorded in cyathostomin populations. It is important that veterinarians re-establish control over the implementation of parasite control programmes, a major objective of which should be the preservation of anthelmintic efficacy. This article details the principles of cyathostomin control in horses with particular reference to anthelmintic resistance, and the use and interpretation of diagnostic tests for detecting cyathostomins and identifying anthelmintic resistance. [ABSTRACT FROM AUTHOR]

A cDNA representing the gene Teladorsagia circumcincta apyrase-1 (Tci-apy-1) was isolated, by PCR, from a T. circumcincta fourth-stage larval (L4) cDNA library. The closest orthologue of this gene is a Ca-dependent apyrase from Ostertagia ostertagi, with 92% amino acid identity across all 339 residues. Tci-apy-1 is transcribed in a stage-specific manner, the transcript being predominant in L4, detectable in the adult cDNA, but absent from eggs and infective third-stage larvae (L3). The protein, Tci-APY-1, was detected by immunoblotting in extracts of L4 nematodes and was present in excretory/secretory products from the same developmental stage. A recombinant version of Tci-APY-1 was expressed in bacteria as an active enzyme that hydrolysed nucleoside triphosphate substrates with a preference of ATP over other nucleoside triphosphates. Recombinant Tci-APY-1 hydrolysed ATP and ADP but not AMP. Apyrase activity was divalent cation-dependent, with no hydrolysis in the presence of Mg, but activation in the presence of Ca. Recombinant Tci-APY-1 was bound by IgG present in serum and both IgG and IgA present in abomasal mucus from trickle-infected, immune sheep but not in material derived from lambs exposed to a single infection. The potential immunomodulatory roles of this Tci-APY-1 are discussed in relation to purinergic signalling. [ABSTRACT FROM AUTHOR]

Summary Horses worldwide are exposed to a complex mixture of intestinal parasitic helminths. When burdens are high, these parasites can seriously compromise health and welfare. Some helminth species have an extremely high prevalence and are difficult to control, not least because there is a limited understanding of their most basic biology. Furthermore, levels of resistance to some of the commonly used anthelmintics are widespread and increasing. The cyathostomins are the most common nematode species affecting equids worldwide. Within this group of parasites are more than 50 different species. Until recent research activities, little was known about the contribution that individual species make to clinical disease, parasite epidemiology and anthelmintic resistance. This review describes some of the recent research advances in the understanding of cyathostomins in these areas. As part of the research effort, molecular tools were developed to facilitate identification of the non-parasitic stages of cyathostomins. These tools have proved invaluable in the investigation of the relative contributions that individual species make to the pathology and epidemiology of mixed infections. At the more applied level, research has also progressed in the development of a diagnostic test that will allow numbers of cyathostomin encysted larvae to be estimated. This test utilises cyathostomin-specific serum antibody responses as markers of infection. As anthelmintic resistance will be the major constraint on parasite control in future, researchers are actively investigating mechanisms of drug resistance and how to improve the detection of resistance in the field. Recent developments in these areas are also outlined. [ABSTRACT FROM AUTHOR]

Wright HJ, Chapple ILC, Matthews JB, Cooper PR. Fusobacterium nucleatum regulation of neutrophil transcription. J Periodont Res 2011; 46: 1-12. © 2010 John Wiley & Sons A/S Abnormal neutrophil responses have been observed in periodontitis patients, including hyper-reactivity in terms of production of reactive oxygen species (ROS) following exposure to the key quorum-sensing plaque bacterium, Fusobacterium nucleatum. This study was designed to characterize the transcriptional response of neutrophils to F. nucleatum. Peripheral blood neutrophils were exposed to F. nucleatum, and gene expression was analysed using high-throughput transcriptomics. Microarray technology demonstrated differential expression of 208 genes (163 increased and 43 decreased relative to control genes), which identified regulation of several ontological classes, including signal transduction (13%), transcription regulation (7%) and ROS response (14%). Individual gene expression analysis of selected transcripts, including CSF, CXCL3, FOS, HMOX1, HSP40, SOD2, NFKB2 and GP91, in individual and pooled RNA samples from control and F. nucleatum-exposed neutrophils corroborated microarray data. Analysis of ROS generation, combined with transcript analysis, in response to a panel of proinflammatory stimuli ( F. nucleatum, Porphyromonas gingivalis, Escherichia coli lipopolysaccharide and opsonized Staphylococcus aureus) identified significant differences in ROS and transcript regulatory control. Further analyses of neutrophils from periodontitis patients and periodontally healthy control subjects stimulated with F. nucleatum indicated significant differential induction of several ROS response-related transcripts. These data demonstrate that neutrophils are transcriptionally active in response to the periodontal pathogen F. nucleatum and that these changes in gene expression are likely to affect neutrophil function. The differential response of neutrophils to a range of stimuli combined with data demonstrating differences between patient and control neutrophils indicate the importance of this cell and its interaction with the local tissue environment in the pathogenesis of periodontitis. [ABSTRACT FROM AUTHOR]

Issue Addressed: the school setting is an important context for the development of children's eating behaviours. As most Australian children (86%) bring their lunch from home, knowledge of what parents provide in home-prepared school lunches can inform efforts to improve their nutritional quality. This study investigated the content of children's home-prepared school lunches, considered variation across the school week, and explored gender and grade level differences.Methods: this observational analysis of children's home-prepared school lunches was conducted in children attending the first three years of school at one of five northern Melbourne metropolitan schools. One hundred and seventy parents (response rate 12%) gave consent for their child's lunch to be audited up to five times (minimum of three) across a one-month period. The food and beverage items of students' school lunches were audited using the School Food Checklist.Results: the average home-prepared school lunch contained a sandwich, a piece of fruit and one and a half servings of extras (low nutritional value and/or high in added fat, salt or sugar). Servings of bread declined (Wilks' Λ=0.82, p=0.01) from Monday to Friday and there were more servings of extras (Wilks' Λ=0.79, p<0.01) on Monday than Wednesday. Younger children's lunches contained fewer servings of fruit (F(2,71.93)=4.84, p=0.03), vegetables (F(2,78.97)=3.86, p<0.05) and bread (F(2,140)=4.36, p=0.02) than those of older children. Girls' lunches contained significantly more vegetables than boys' lunches, (t(154.51)=-2.21, p=0.03).Conclusions: lunches were high in extras and low in servings of vegetables and other healthy snacks with minor variations in the quantity of bread and extras across the school week. [ABSTRACT FROM AUTHOR]

A macrophage migration inhibitory factor (MIF)-like molecule, Tci-MIF-1, was isolated from Teladorsagia circumcincta and subjected to detailed characterization. A cDNA representing Tci-mif-1 was isolated following its identification in third-stage larvae (L3)-enriched cDNA population. Sequencing of the cDNA indicated a 348-bp open reading frame (ORF) with the closest orthologue being a MIF derived from the human hookworm Ancylostoma ceylanicum. Messenger RNA (mRNA) representing the Tci-MIF-1 transcript was detected in eggs, L3 and adult stages of T. circumcincta. The transcript was also present, but to a lesser extent in fourth-stage larvae (L4). Detection of Tci-MIF-1 protein in T. circumcincta developmental stages reflected the transcript levels identified by reverse transcriptase-PCR. Using immunohistochemistry, the Tci-MIF-1 protein was shown to have a diffuse distribution in L3 tissue, and in L4 and adult stages, the protein was localized to the nematode gut. A recombinant version of Tci-MIF-1 was produced, and enzymic assays indicated that this recombinant protein and a somatic extract of L3 possessed dopachrome tautomerase activity as has been observed previously in other MIF-like molecules. Neither native, purified Tci-MIF nor recombinant Tci-MIF-1 dramatically influenced the in vitro migration of sheep monocytes. [ABSTRACT FROM AUTHOR]

Background: Assessment of children's diets is problematic, typically relying on error-prone parent or child recall or reporting, or resource intensive direct observation. The School Food Checklist (SFC) is an objective instrument comprising of 20 food and beverage categories designed to measure the foods contained in children's packed lunches. The present study aimed to assess intra-rater and inter-rater reliability of each of the food and beverage categories of the SFC for both in-school audits and photograph analysis of children's school lunches. Methods: Participants comprised 176 children aged 5-8 years from five primary schools in Northern Metropolitan Melbourne. The SFC was used to measure the foods contained in children's packed lunches in the school setting and using photographs. Photograph analysis was conducted by the auditors 2-3 months after completion of in-school audits. Results: Both intra-rater [intra-class correlation coefficient (ICC) = 0.78-1] and inter-rater (ICC = 0.50-0.95) reliability analysis indicated strong agreement for in-school auditing. With the exception of the food category titled 'leftovers', there was strong intra-rater reliability for auditors' live audits and their analysis of photographs [ICC = 0.57-0.98 (Auditor 1); ICC = 0.72-0.90 (Auditor 2)], and strong inter-rater reliability for photograph analysis (ICC = 0.68-0.92). Conclusions: The SFC is a reliable method of measuring the foods and beverages contained in children's packed lunches when used in the school setting or for photograph analysis. This finding has broad implications, particularly for the use of photograph analysis, because this approach offers a convenient and cost effective method of measuring what food and beverages children bring to school in home packed lunches. [ABSTRACT FROM AUTHOR]

Parasitic nematodes of the small-ruminant gastrointestinal tract pose a problem worldwide. The impact of these pathogens is worsened by the emergence of anthelmintic resistance to all three available classes of drugs. In addition to causing considerable economic loss, these parasites are detrimental to the health and welfare of sheep and goats. Vaccination offers an alternative approach to drug-based control and a great deal of investment has gone into the investigation of protective antigens for some of these nematode species. However, attempts at vaccination are hindered by a lack of understanding of how best to promote protective immunity to nematode species, such as Teladorsagia circumcincta, which inhabits the abomasum of sheep. This situation contrasts with that in murine models of gastrointestinal nematode infection, where the basis of protective immunity is increasingly well understood. In this review, we discuss the current knowledge of the immune effector mechanisms elicited by T. circumcincta and consider the probable role of dendritic cells in the initiation of both effector and regulatory responses in the abomasum. [ABSTRACT FROM AUTHOR]

Aims: Albiglutide is a glucagon-like peptide-1 (GLP-1) mimetic generated by genetic fusion of a dipeptidyl peptidase-IV-resistant GLP-1 dimer to human albumin. Albiglutide was designed to retain the therapeutic effects of native GLP-1 while extending its duration of action. This study was conducted to determine the pharmacokinetics and initial safety/tolerability profile of albiglutide in non-diabetic volunteers. Methods: In this single-blind, randomized, placebo-controlled trial, 39 subjects (18–60 years, body mass index 19.9–35.0 kg/m2) received placebo (n = 10) or escalating doses of albiglutide (n = 29) on days 1 and 8 in the following sequential cohorts: cohort 1: 0.25 + 1 mg; cohort 2: 3 + 6 mg; cohort 3: 16 + 24 mg; cohort 4: 48 + 60 mg; and cohort 5: 80 + 104 mg. Dose proportionality was evaluated based on area under the plasma drug concentration versus time curve [area under the curve (AUC(0–7 days))] and maximum plasma drug concentration ( Cmax) for cohorts 2–5 during week 1. Results: Albiglutide had a terminal elimination half-life ( T1/2) of 6–8 days and time to maximum observed plasma drug concentration ( Tmax) of 3–4 days. A greater-than-dose proportional increase in albiglutide exposure was observed. Albiglutide demonstrated a dose-dependent trend in reductions of glucose weighted mean AUC and fructosamine levels in healthy subjects. The incidence and severity of adverse events (AEs) was similar between placebo and albiglutide groups. Headache was the most frequent drug-related AE, followed by constipation, flatulence and nausea. Conclusions: Albiglutide has a half-life that favours once weekly or less frequent dosing with an acceptable safety/tolerability profile in non-diabetic subjects. [ABSTRACT FROM AUTHOR]

Teladorsagia circumcincta is an important parasitic nematode of domestic small ruminants. Drug resistance in this species is common so alternative methods of control are required. As animals develop immunity to T. circumcincta, vaccination is a valid option. Little is known about the antigens that play a role in stimulating immunity at this host/parasite interface. As responses generated between 1 and 5 dpi are known to affect development of these nematodes in their gastric niche, we focused on proteins released during the early stages of infection. To identify molecules potentially involved in immunity, we undertook a proteomics analysis of proteins released from larvae harvested at 1-, 3- and 5-days post-infection (dpi). This analysis produced peptide sequence data that was used to search information available in T. circumcincta expressed sequence tag (EST) databases and enabled identification of a number of excretory/secretory (ES) proteins. Immunoblots were performed to assess the relative molecular weight of ES antigens that were targets of local IgA responses in mucus from sheep rendered immune to infection. ELISA was performed to assess antigen-specific mucus IgA levels in individual sheep. These experiments provided preliminary evidence that the proteins identified in the larval secretome were subject to these antibody responses. [ABSTRACT FROM AUTHOR]

A cDNA encoding a surface-associated antigen was amplified by reverse transcriptase polymerase chain reaction (PCR) from RNA extracted from Teladorsagia circumcincta exsheathed third stage larvae (xL3). The protein encoded by this cDNA, Tc -SAA-1, displays 77% identity over 162 amino acid residues to a surface associated antigen from Ancylostoma caninum (Ac- SAA-1). Antiserum raised against a bacterially-expressed recombinant form of Tc -SAA-1 reacted with a native protein in somatic and surface extracts of xL3 but not with L4 or adult parasites. Limited binding of anti SAA-1 antibody was observed on the cuticular surface of xL3 s, however, regions of localization underlying the cuticle were observed. Incubation of xL3 T. circumcincta with anti-SAA rabbit serum failed to significantly inhibit penetration of the abomasal mucosa in vitro. IgA in abomasal mucus derived from sheep that had received a trickle infection of T. circumcincta bound recombinant Tc -SAA-1. [ABSTRACT FROM AUTHOR]