Evaluating the prospective utility of pharmacogenetics reporting among Canadian Armed Forces personnel receiving pharmacotherapy: a preliminary assessment towards precision psychiatric care.

Pharmacological interventions for treating posttraumatic stress disorder in Canadian Armed Forces (CAF) members and Veterans often achieve modest results. The field of pharmacogenetics, or the study of how genes influence an individual's response to different medications, offers insight into how prior knowledge of gene-drug interactions may potentially improve the trial-and-error process of drug selection in pharmacotherapy, thereby improving treatment effects and remission rates. Given the relative recency of pharmacogenetics testing and sparse research in military samples, we used pharmacogenetics testing in a small pilot group (n=23) of CAF members and Veterans who were already engaged in pharmacotherapy for a service-related mental health condition to better understand the associated opportunities and challenges of pharmacogenetics testing in this population. Our preliminary evaluation involved: (1) reporting the prevalence of pharmacogenetics testing 'bin' status according to participants' reports ('green', 'yellow' or 'red'; intending to signal 'go', 'caution' or 'stop', regarding the potential for gene-drug interactions); (2) calculating the percentage of currently prescribed psychotropic medications that were assessed and included in the reports; (3) evaluating whether prescribers used pharmacogenetics testing information according to clinical notes and (4) collecting informal feedback from participating psychiatrists. While pharmacogenetics testing appeared to provide valuable information for a number of clients, a major limitation was the number of commonly prescribed medications not included in the reports.

Effect of remote ischemic conditioning on the immune-inflammatory profile in patients with traumatic hemorrhagic shock in a randomized controlled trial.

Resuscitation induced ischemia/reperfusion predisposes trauma patients to systemic inflammation and organ dysfunction. We investigated the effect of remote ischemic conditioning (RIC), a treatment shown to prevent ischemia/reperfusion injury in experimental models of hemorrhagic shock/resuscitation, on the systemic immune-inflammatory profile in trauma patients in a randomized trial. We conducted a prospective, single-centre, double-blind, randomized, controlled trial involving trauma patients sustaining blunt or penetrating trauma in hemorrhagic shock admitted to a Level 1 trauma centre. Patients were randomized to receive RIC (four cycles of 5-min pressure cuff inflation at 250 mmHg and deflation on the thigh) or a Sham intervention. The primary outcomes were neutrophil oxidative burst activity, cellular adhesion molecule expression, and plasma levels of myeloperoxidase, cytokines and chemokines in peripheral blood samples, drawn at admission (pre-intervention), 1 h, 3 h, and 24 h post-admission. Secondary outcomes included ventilator, ICU and hospital free days, incidence of nosocomial infections, 24 h and 28 day mortality. 50 eligible patients were randomized; of which 21 in the Sham group and 18 in the RIC group were included in the full analysis. No treatment effect was observed between Sham and RIC groups for neutrophil oxidative burst activity, adhesion molecule expression, and plasma levels of myeloperoxidase and cytokines. RIC prevented significant increases in Th2 chemokines TARC/CCL17 (P < 0.01) and MDC/CCL22 (P < 0.05) at 24 h post-intervention in comparison to the Sham group. Secondary clinical outcomes were not different between groups. No adverse events in relation to the RIC intervention were observed. Administration of RIC was safe and did not adversely affect clinical outcomes. While trauma itself modified several immunoregulatory markers, RIC failed to alter expression of the majority of markers. However, RIC may influence Th2 chemokine expression in the post resuscitation period. Further investigation into the immunomodulatory effects of RIC in traumatic injuries and their impact on clinical outcomes is warranted.ClinicalTrials.gov number: NCT02071290.

Massive open online courses (MOOCs) as a window into the veterinary profession.

Massive open online courses (MOOCs) are freely available online courses open to anyone who registers and typically are associated with thousands or hundreds of thousands of participants. Using an established online platform, the authors created and delivered a five-week MOOC aimed primarily at prospective veterinary students, but open to anyone with an interest in finding out more about the veterinary profession in general. 11,911 people signed up for the course, and of these, 8137 interacted in some way with the course and 1716 received a certificate of completion. The majority of participants (84 per cent) were female, and there was a wide age range (under 18 to over 65). Most participants were from North America or the UK. 65 per cent of those completing the entry survey were hoping or intending to work in the vet profession in the future, while 33 per cent were not. Qualitative data indicated that the course was helpful in aiding those undecided as to whether they wanted to be a veterinarian or not to decide one way or another whether they want to pursue veterinary medicine as a career. Furthermore, the course was seen as being a useful introduction to the veterinary profession even for those who had no intention of working in the field.

Timing of Maternal Exposure and Foetal Sex Determine the Effects of Low-level Chemical Mixture Exposure on the Foetal Neuroendocrine System in Sheep.

We have shown that continuous maternal exposure to the complex mixture of environmental chemicals (ECs) found in human biosolids (sewage sludge), disrupts mRNA expression of genes crucial for development and long-term regulation of hypothalamic-pituitary gonadal (HPG) function in sheep. The present study investigated whether exposure to ECs only during preconceptional period or only during pregnancy perturbed key regulatory genes within the hypothalamus and pituitary gland and whether these effects were different from chronic (life-long) exposure to biosolid ECs. The findings demonstrate that the timing and duration of maternal EC exposure influences the subsequent effects on the foetal neuroendocrine system in a sex-specific manner. Maternal exposure prior to conception, or during pregnancy only, altered the expression of key foetal neuroendocrine regulatory systems such as gonadotrophin-releasing hormone and kisspeptin to a greater extent than when maternal exposure was 'life-long'. Furthermore, hypothalamic gene expression was affected to a greater extent in males than in females and, following EC exposure, male foetuses expressed more 'female-like' mRNA levels for some key neuroendocrine genes. This is the first study to show that 'real-life' maternal exposure to low levels of a complex cocktail of chemicals prior to conception can subsequently affect the developing foetal neuroendocrine system. These findings demonstrate that the developing neuroendocrine system is sensitive to EC mixtures in a sex-dimorphic manner likely to predispose to reproductive dysfunction in later life.

Taxonomic revision of Phascogale tapoatafa (Meyer, 1793) (Dasyuridae; Marsupialia), including descriptions of two new subspecies and confirmation of P. pirata Thomas, 1904 as a 'Top End' endemic.

The Australian Brush-tailed Phascogale (Phascogale tapoatafa sensu lato) has a broad but highly fragmented distribution around the periphery of the Australian continent and all populations are under significant ongoing threat to survival. A new appraisal of morphological and molecular diversity within the group reveals that the population in the 'Top End' of the Northern Territory is specifically distinct from all others, including those in the Kimberley region of Western Australia to the west and on Cape York of Queensland to the east. The name P. pirata Thomas, 1904 is available for the 'Top End' taxon. Three geographically disjunct populations are distinguished at subspecies level within P. tapoatafa on a suite of external and cranio-dental features; these are found in southeast Australia from South Australia to mid-coastal Queensland (nominotypical tapoatafa), southwest Western Australia (wambenger subsp. nov.), and the Kimberley region of Western Australia (kimberleyensis subsp. nov.). A potential fourth subspecies occurs on Cape York but remains too poorly represented in collections for adequate characterization. Molecular divergence estimates based on partial sequences of the mitochondrial cytochrome b gene indicate that the range disjunction across southern Australia probably dates from the Late Pliocene, with the multiple disjunctions across northern Australia being more recent though almost certainly exceeding 400,000 years. An argument is made for the continued use of the subspecies rank in Australian mammalogy, despite a general lack of consistency in its current application.

Comparison of anaesthesia 'Day 1 skills' expectations between veterinary anaesthetists and general practitioners.

Day One Skills (DOS) were introduced by the Royal College of Veterinary Surgeons (RCVS) in 2006 as a guideline for minimum skills required by a veterinary graduate. However, the RCVS anaesthesia DOS are broad and do not specify differences in skills required for different species. The aims of this study were: (1) to determine which anaesthesia skills were considered essential for day one practice by UK-based veterinary practitioners (GPs) and anaesthetists; and (2) to explore current opinions on veterinary undergraduate anaesthesia training. Questionnaires for veterinary GPs (QGPs) and veterinary anaesthetists (QVAs) were developed which asked general information on expectations of anaesthesia skills as well as specific expectations for the common veterinary species. Fifty-five UK-based members of the Association of Veterinary Anaesthetists responded, with a random sample of veterinary practices stratified by UK county generating 234 responses and a convenience sample targeted at more specialist veterinary specialities in the UK generating 161 responses. There was close overall agreement between the two groups of GPs and anaesthetists on essential anaesthesia DOS. However, expectations varied with species-greatest in cats and dogs, lowest in exotics. Many respondents commented that new veterinary graduates lack practical skills and should not be expected to be omnicompetent across all species. In conclusion, anaesthesia undergraduate training should prioritise essential practical DOS.

Association of trauma exposure with proinflammatory activity: a transdiagnostic meta-analysis.

Exposure to psychological trauma (for example, childhood/early life adversity, exposure to violence or assault, combat exposure, accidents or natural disasters) is known to increase one's risk of developing certain chronic medical conditions. Clinical and population studies provide evidence of systemic inflammatory activity in trauma survivors with various psychiatric and nonpsychiatric conditions. This transdiagnostic meta-analysis quantitatively integrates the literature on the relationship of inflammatory biomarkers to trauma exposure and related symptomatology. We conducted random effects meta-analyses relating trauma exposure to log-transformed inflammatory biomarker concentrations, using meta-regression models to test the effects of study quality and psychiatric symptomatology on the inflammatory outcomes. Across k=36 independent samples and n=14,991 participants, trauma exposure was positively associated with C-reactive protein (CRP), interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α (mean rs =0.2455, 0.3067, 0.2890, and 0.2998, respectively). No significant relationships were noted with fibrinogen, IL-2, IL-4, IL-8, or IL-10. In meta-regression models, the presence of psychiatric symptoms was a significant predictor of increased effect sizes for IL-1ß and IL-6 (ß=1.0175 and 0.3568, respectively), whereas study quality assessment scores were associated with increased effect sizes for IL-6 (ß=0.3812). Positive correlations between inflammation and trauma exposure across a range of sample types and diagnoses were found. Although reviewed studies spanned an array of populations, research on any one specific psychiatric diagnosis was generally limited to one or two studies. The results suggest that chronic inflammation likely represents one potential mechanism underlying risk of health problems in trauma survivors.

Reproduction Symposium: does grazing on biosolids-treated pasture pose a pathophysiological risk associated with increased exposure to endocrine disrupting compounds?

Biosolids (processed human sewage sludge), which contain low individual concentrations of an array of contaminants including heavy metals and organic pollutants such as polycyclic aromatic hydrocarbons (PAH), polychlorinated biphenyls (PCB), and polychlorinated dibenzodioxins/polychlorinated dibenzofurans known to cause physiological disturbances, are increasingly being used as an agricultural fertilizer. This could pose a health threat to both humans and domestic and wild animal species. This review summarizes results of a unique model, used to determine the effects of exposure to mixtures of environmentally relevant concentrations of pollutants, in sheep grazed on biosolids-treated pastures. Pasture treatment results in nonsignificant increases in environmental chemical (EC) concentrations in soil. Whereas EC concentrations were increased in some tissues of both ewes and their fetuses, concentrations were low and variable and deemed to pose little risk to consumer health. Investigation of the effects of gestational EC exposure on fetal development has highlighted a number of issues. The results indicate that gestational EC exposure can adversely affect gonadal development (males and females) and that these effects can impact testicular morphology, ovarian follicle numbers and health, and the transcriptome and proteome in adult animals. In addition, EC exposure can be associated with altered expression of GnRH, GnRH receptors, galanin receptors, and kisspeptin mRNA within the hypothalamus and pituitary gland, gonadotroph populations within the pituitary gland, and regional aberrations in thyroid morphology. In most cases, these anatomical and functional differences do not result in altered peripheral hormone concentrations or reproductive function (e.g., lambing rate), indicating physiological compensation under the conditions tested. Physiological compensation is also suggested from studies that indicate that EC effects may be greater when exposure occurs either before or during gestation compared with EC exposure throughout life. With regard to human and animal health, this body of work questions the concept of safe individual concentration of EC when EC exposure typically occurs as complex mixtures. It suggests that developmental EC exposure may affect many different physiological systems, with some sex-specific differences in EC sensitivity, and that EC effects may be masked under favorable physiological conditions.

Stakeholder consultation on tracking in UK veterinary degrees: part 2.

There is ongoing debate in the profession as to whether veterinary students should focus on one (or a small number of) species during their undergraduate training (ie, track). This paper presents the qualitative data from surveys evaluating UK stakeholder opinion on introducing partial tracking (whereby students continue to qualify able to practise in all species) and full tracking (students qualify in a limited number of species with restricted registration). Surveys were distributed to practitioners, students and university staff; 1061 responses were completed. Thematic framework analysis was conducted on the free-text responses; responses were coded to a hierarchical framework developed inductively from the data. Six major themes were identified: choice, flexibility, competency and knowledge, stakeholder implications, specialisation and 'what is a vet?'. The majority of the themes related to both full and partial tracking, usually being more pronounced in full tracking. The theme 'choice' is particularly important in light of the study's quantitative findings on students' awareness of the profession and their career aspirations (presented in a previous paper); should tracking be implemented, veterinary schools will need to take a proactive role in educating and assisting students while making career choices.

Stakeholder consultation on tracking in UK veterinary degrees: part 1.

There is on-going debate regarding whether veterinary students should focus on one (or a small number of) species during their undergraduate training (ie, track). The aims of this study were to: evaluate UK stakeholders' opinion on partial tracking (whereby students continue to qualify able to practise in all species) and full tracking (students qualify in a limited number of species necessitating restricted registration); and evaluate students' career aspirations in relation to the UK veterinary profession's employment profile. This paper presents the quantitative results of surveys completed by practitioners, students and university staff. The majority of respondents (69.4 per cent) disagreed or strongly disagreed with full tracking, however, there was widespread support for partial tracking (79.0 per cent agreed or strongly agreed). Students favoured partial tracking more so than practitioners (P<0.001). Univariate analysis of demographic factors did not identify differences in opinion regarding tracking within stakeholder groups. Students' knowledge of the UK veterinary employment profile appeared accurate. However, their career aspiration changed with year of the course, and only final year students' intentions were aligned with the profession's current profile. Qualitative data from these surveys are presented in a second paper and include the advantages, disadvantages and implications of partial and full tracking.

Neural network integration of field observations for soil endocrine disruptor characterisation.

A neural network approach was used to predict the presence and concentration of a range of endocrine disrupting compounds (EDCs), based on field observations. Soil sample concentrations of endocrine disrupting compounds (EDCs) and site environmental characteristics, drawn from the National Soil Inventory of Scotland (NSIS) database, were used. Neural network models were trained to predict soil EDC concentrations using field observations for 184 sites. The results showed that presence/absence and concentration of several of the EDCs, mostly no longer in production, could be predicted with some accuracy. We were able to predict concentrations of seven of 31 compounds with r(2) values greater than 0.25 for log-normalised values and of eight with log-normalised predictions converted to a linear scale. Additional statistical analyses were carried out, including Root Mean Square Error (RMSE), Mean Error (ME), Willmott's index of agreement, Percent Bias (PBIAS) and ratio of root mean square to standard deviation (RSR). These analyses allowed us to demonstrate that the neural network models were making meaningful predictions of EDC concentration. We identified the main predictive input parameters in each case, based on a sensitivity analysis of the trained neural network model. We also demonstrated the capacity of the method for predicting the presence and level of EDC concentration in the field, identified further developments required to make this process as rapid and operator-friendly as possible and discussed the potential value of a system for field surveys of soil composition.

Long term temporal and spatial changes in the distribution of polychlorinated biphenyls and polybrominated diphenyl ethers in Scottish soils.

Long term changes in polychlorinated biphenyl (PCB) and polybrominated diphenyl ether (PBDE) concentrations in soil from four transects across Scotland were measured in three surveys conducted between 1990 and 2007-9. Overall PCB level declined during this period (22.5 to 4.55 ng/g, p<0.001) but PBDEs increased (0.68 to 2.55 ng/g, p<0.001), reflecting the ban on PCB use in the 1980s while PBDE use increased until about 2004 when the use of penta-mix congener ceased in Europe. The proportion of lighter PCB congeners (28+52) present declined (p<0.001) primarily between 1990 and 1999. However, the proportion of lighter PBDE congeners (47+99) in the soil samples increased (p<0.01) from 1990 to 1999 and declined (p<0.001) thereafter, probably reflecting the introduction of legislation banning penta-BDE products and the degradation of lighter congeners and their translocation. PCBs were slightly higher in two southernmost transects but PBDE concentrations were significantly higher (p<0.001) in the two southern transects than in the two northern transects. This may reflect proximity to areas of high population and industrial activity. It is concluded that temporal and spatial changes in the distribution of PCBs and PBDEs reflect geography, physical processes and legislation.

The influence of interview on decision making and selection of prospective veterinary undergraduate students.

Interviews form part of the selection process in many veterinary programmes worldwide. This study aimed to evaluate the influence of the interview on veterinary selection decisions. An admissions cycle of interviews of 181 shortlisted school-leaving applicants to veterinary medicine was investigated. Selection panel pairs (from cohorts of 5 chairs and 11 cointerviewers) independently evaluated applicants before interview on the basis of their written application. Applicants were then interviewed and selectors repeated their evaluations, both independently and after joint discussion. Results of the preinterview and postinterview evaluations of the applicants were analysed statistically. There was slight to moderate agreement between the chair and cointerviewer on selection decisions/rankings taken before interview, but substantial agreement after interview. Agreement between postinterview decisions/rankings and consensus decisions/rankings postinterview was extremely high. Applicant attributes that had the most influence on selection decisions were: 'communication skills', 'overall knowledge gained from work experience' and 'ability to think on their feet'. There was significantly more agreement possible between interviewers with regard to selection decisions based on interview assessment compared with preinterview assessment of written applications. This study suggests that interviews may be a useful and important aid in decision making for selecting the candidates perceived as most suitable for this veterinary programme.

Short- and long-term temporal changes in soil concentrations of selected endocrine disrupting compounds (EDCs) following single or multiple applications of sewage sludge to pastures.

Temporal changes in soil burdens of selected endocrine disrupting compounds were determined following application to pasture of either sewage sludge or inorganic fertilizer. Soil polycyclic aromatic hydrocarbon and polychlorinated biphenyl concentrations were not altered. Changes in concentrations of diethylhexyl phthalate (DEHP) and PBDEs 47 and 99 differed with season but concentrations remained elevated for more than three weeks after application, when grazing animals are normally excluded from pasture. It is concluded that single applications of sewage sludge can increase soil concentrations of some, but not all classes of EDCs, possibly to concentrations sufficient to exert biological effects when different chemicals act in combination, but patterns of change depend on season and soil temperature. Analysis of soil from pasture subjected to repeated sludge applications, over 13 years, provided preliminary evidence of greater increases in soil burdens of all of the EDC groups measured, including all of the PBDE congeners measured.

Concentrations and geographic distribution of selected organic pollutants in Scottish surface soils.

Concentrations of selected persistent organic pollutants (POPs) representing three chemical classes (polycyclic aromatic hydrocarbons (PAH), polybrominated diphenyl ethers (PBDE) and polychlorinated biphenyls (PCB) and the organic pollutant diethylhexyl phthalate (DEHP), were determined in surface soil samples (0-5 cm) collected at 20 km grid intersects throughout Scotland over a three-year period. Detectable amounts of all chemical classes and most individual congeners were present in all samples. There were no consistent effects of soil or vegetation type, soil carbon content, pH, altitude or distance from centres of population on concentrations which exhibited extreme variation, even in adjacent samples. It is concluded that soil POPs and DEHP concentrations and associated rates of animal and human exposure were highly variable, influenced by multiple, interacting factors, and not clearly related to local sources but possibly related to wet atmospheric deposition and the organic carbon content of the soil.

Effects of exposure to environmental chemicals during pregnancy on the development of the male and female reproductive axes.

There is a large body of literature describing effects of environmental chemicals (ECs), many of them anthropogenic with endocrine-disrupting properties, on development in rodent laboratory species, some of which lead to impaired reproduction and adverse health. This literature joins extensive human epidemiological data and opportunistic wildlife findings on health effects of ECs. In contrast, the effect of endocrine disruption on foetal development and reproductive performance in domestic species is less extensively documented. This applies both to domestic farm and to companion species even though the former is critical to food production and the latter share our homes and many aspects of the modern developed human lifestyle. In domestic species, the nature of chemicals exposure in utero and their consequences for animal health and production are poorly understood. A complication in our understanding is that the pace of development, ontogeny and efficiency of foetal and maternal hepatic and placental activity differs between domestic species. In many ways, this reflects the difficulties in understanding human exposure and consequences of that exposure for the foetus and subsequent adult from epidemiological and largely rodent-based data. It is important that domestic species are included in research into endocrine disruption because of their (i) wide variety of exposure to such chemicals, (ii) greater similarity of many developmental processes to the human, (iii) economic importance and (iv) close similarities to developed world human lifestyle in companion species.

Potential barriers to veterinary student access to counselling and other support systems: perceptions of staff and students at a UK veterinary school.

Considerable evidence suggests that veterinary surgeons' mental health is often poorer than comparable populations and that the incidence of suicide is higher among veterinary surgeons than the general public. Veterinary students also appear to suffer from high levels of anxiety and stress, and may possess inadequate coping strategies when faced with adversity. Veterinary students may find it difficult to access central university support systems due to their heavy workload and geographical isolation on some veterinary campuses. A previous study of University of Edinburgh fourth-year veterinary students found that support services located several miles from the main veterinary campus was a barrier to students accessing counselling services. Consequently, a pilot project was initiated, which provided a counselling service at the University of Edinburgh's rural Easter Bush veterinary campus one afternoon a week during 2010. As part of the evaluation of this service, web-based questionnaires were delivered via e-mail to all veterinary staff and students towards the end of the 12-month pilot period to evaluate perceptions of barriers to student counselling and to investigate student-valued support services. Questionnaire responses were received from 35 per cent of veterinary students and 52 per cent of staff. Stigmatisation of being unable to cope was a potent inhibitor of seeking support within the veterinary environment, but counselling was perceived as valuable by the majority of staff and students. Provision of an on-site counselling service was considered important for increasing ease of access; however, students viewed friends and family as their most important support mechanism. Workload was cited as the main cause of veterinary student stress. The majority of staff and student respondents perceived veterinary students as having an increased need for counselling support compared with other students.

Foetal and post-natal exposure of sheep to sewage sludge chemicals disrupts sperm production in adulthood in a subset of animals.

Exposure to ubiquitous, environmental chemicals (ECs) has been hypothesized as a cause for declining male reproductive health. Understanding the long-term effects of EC exposure on reproductive health in humans requires animal models and exposure to 'real life', environmentally relevant, mixtures during development, a life stage of particular sensitivity to ECs. The aim of this study was to evaluate the effects of in utero and post-natal exposure to environmentally relevant levels of ECs, via sewage sludge application to pasture, on the adult male sheep testis. Hormones, liver concentrations of candidate ECs and Sertoli and germ cell numbers in testes of adult rams that were exposed to ECs in sewage sludge in utero, and until weaning via maternal exposure, and post-weaning via grazing pastures fertilized with sewage sludge, were quantified. Evaluated as a single group, exposure to sludge ECs was without significant effect on most parameters. However, a more detailed study revealed that 5 of 12 sludge-exposed rams exhibited major spermatogenic abnormalities. These consisted of major reductions in germ cell numbers per testis or per Sertoli cell and more Sertoli cell-only tubules, when compared with controls, which did not show any such changes. The sludge-related spermatogenic changes in the five affected animals were significantly different from controls (p < 0.001); Sertoli cell number was unaffected. Hormone profiles and liver candidate EC concentrations were not measurably affected by exposure. We conclude that developmental exposure of male sheep to real-world mixtures of ECs can result in major reduction in germ cell numbers, indicative of impaired sperm production, in a proportion of exposed males. The individual-specific effects are presumed to reflect EC effects on a heterogeneous population in which some individuals may be more susceptible to adverse EC effects. Such effects of EC exposure in humans could have adverse consequences for sperm counts and fertility in some exposed males.

Effect of duration of exposure to sewage sludge-treated pastures on liver tissue accumulation of persistent endocrine disrupting compounds (EDCs) in sheep.

Liver tissue concentrations of selected polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and polycyclic aromatic hydrocarbons (PAHs) were determined in groups of Texel ewes and lambs following exposure to pastures fertilised with either sewage sludge (Treated; T) or inorganic fertiliser (Control; C). Lambs were slaughtered at the age of 6 months, in each of 3 years, while ewes were slaughtered at 5 to 6 years of age having been exposed to the respective pastures for approximately 6, 18 or 30 months, during the same, respective years, immediately before slaughter. Mean liver concentrations of very few of the chemical classes were elevated in either ewe or lamb tissue as a result of exposure of the animals to sewage sludge. Mean concentrations, in lamb liver, of chemicals of each of the classes differed significantly, but inconsistently, between years, reflecting temporal variations in exposure, although the pattern of annual change differed with individual chemical. On the other hand, in ewes, liver concentrations of many chemicals increased, significantly and consistently, with increasing duration of exposure. It was concluded that the increases in tissue concentrations with increased duration of exposure were unlikely to be sufficient to be of concern to consumers and that tissue burdens cannot be linked, easily, with the physiological effects reported previously for animals similarly exposed.