Anomalous low-temperature proton conductivity enhancement in a novel protonic nanocomposite.

A novel protonic ceramic composite is synthesized that comprises nanoscale nickel metal films partially decorating the grain boundaries of the proton-conducting ceramic, BaCe0.7Zr0.1Y0.1Yb0.1O3-δ (BCZYYb). Low-temperature proton conductivity improvements of up to 46× vs. a control are observed, suggesting a novel method to enhance ion conductivity in polycrystalline materials.

Chest radiography for predicting the cause of febrile illness among inpatients in Moshi, Tanzania.

AIM: To describe chest radiographic abnormalities and assess their usefulness for predicting causes of fever in a resource-limited setting. MATERIALS AND METHODS: Febrile patients were enrolled in Moshi, Tanzania, and chest radiographs were evaluated by radiologists in Tanzania and the United States. Radiologists were blinded to the results of extensive laboratory evaluations to determine the cause of fever. RESULTS: Of 870 febrile patients, 515 (59.2%) had a chest radiograph available; including 268 (66.5%) of the adolescents and adults, the remainder were infants and children. One hundred and nineteen (44.4%) adults and 51 (20.6%) children were human immunodeficiency virus (HIV)-infected. Among adults, radiographic abnormalities were present in 139 (51.9%), including 77 (28.7%) with homogeneous and heterogeneous lung opacities, 26 (9.7%) with lung nodules, 25 (9.3%) with pleural effusion, 23 (8.6%) with cardiomegaly, and 13 (4.9%) with lymphadenopathy. Among children, radiographic abnormalities were present in 87 (35.2%), including 76 (30.8%) with homogeneous and heterogeneous lung opacities and six (2.4%) with lymphadenopathy. Among adolescents and adults, the presence of opacities was predictive of Streptococcus pneumoniae and Coxiella burnetii, whereas the presence of pulmonary nodules was predictive of Histoplasma capsulatum and Cryptococcus neoformans. CONCLUSIONS: Chest radiograph abnormalities among febrile inpatients are common in northern Tanzania. Chest radiography is a useful adjunct for establishing an aetiologic diagnosis of febrile illness and may provide useful information for patient management, in particular for pneumococcal disease, Q fever, and fungal infections.

Use of computed tomography sinography for evaluation of draining tracts in 27 dogs and one cat.

OBJECTIVES: To describe the clinical findings, imaging findings and outcome in patients in which CT sinography was performed, and assess to what degree this technique adds information about the extent of a tract or increases the accuracy of diagnosis of foreign bodies on CT. MATERIALS AND METHODS: Retrospective review of medical records of 27 dogs and one cat with draining tracts that had CT sinography. Pre- and post-intravenous (IV) contrast CT series were compared with CT sinography in each patient. RESULTS: Median duration of clinical signs before referral was 85 days (range 2 to 1478 days). The most common reported clinical signs were swelling (14/28, 50%) and regional pain (5/28, 18%). CT sinography revealed a more extensive tract than post-IV contrast CT in 21% cases. On post-IV contrast CT, 31% of foreign bodies were detected compared to 23% on CT sinography. All four foreign bodies detected by CT were observed in the non-contrast images. Surgery was performed after CT in 22 (79%) cases. Thirteen (46%) draining tracts resolved after surgery, three (11%) resolved without surgery, six (21%) persisted or recurred after surgery, and six (21%) were lost to follow-up. CLINICAL SIGNIFICANCE: CT sinography provides limited additional information about the extent of draining tracts compared to pre- and post-IV contrast CT images and did not increase the number of foreign bodies identified.

Acute and chronic stress-like levels of cortisol inhibit the oestradiol stimulus to induce sexual receptivity but have no effect on sexual attractivity or proceptivity in female sheep.

Stress-like levels of cortisol inhibit sexual receptivity in ewes but the mechanism of this action is not understood. One possibility is that cortisol interferes with the actions of oestradiol to induce sexual receptivity. We tested this hypothesis in 2 experiments with ovariectomised ewes that were artificially induced into oestrus by 12 days of i.m. injections of progesterone followed by an i.m. injection of oestradiol benzoate (ODB) 48 h later. In Experiment 1, ewes were randomly allocated to the following groups: saline infusion+25 µg ODB, saline infusion+50 µg ODB, cortisol infusion+25 µg ODB or cortisol infusion+50 µg ODB (n=5 per group). Saline or cortisol was infused i.v. for 40 h beginning at the ODB injection. In Experiment 2, ewes were infused with saline or cortisol (n=5 per group) for 5h beginning 1h before ODB injection. In both experiments, ewe sexual behaviour (attractivity, proceptivity and receptivity) was quantified every 6h. Blood samples were also collected. The cortisol infusion yielded plasma concentrations of cortisol similar to those seen during psychosocial stress. In both experiments, cortisol suppressed receptivity index (number of immobilisations by ewe/courtship displays by ram) and the number of times ewes were mounted but had no effect on attractivity or proceptivity, irrespective of the dose of ODB (Experiment 1). Cortisol also suppressed LH pulse amplitude. These results suggest that both an acute (5h) and chronic (40 h) infusion of cortisol inhibit oestradiol-induced sexual receptivity in ewes and that increasing the dose of ODB does not overcome the inhibitory effects of cortisol.

Clinical administration of microneedles: skin puncture, pain and sensation.

Injections using hypodermic needles cause pain, discomfort, localised trauma and apprehension. Additionally, careful use and disposal of needles is required to avoid transmission of blood-borne pathogens. As an alternative, microneedles can facilitate drug delivery without significantly impacting on pain receptors or blood vessels that reside beneath the skin outer layers. In this study we aim to determine the pain and sensory response to the application of wet-etch silicon microneedles, when used in such a way as to reliably penetrate skin, and provide a preliminary indication of how skin responds to microneedle injury with time. Twelve subjects received single-blinded insertions of a 25-G hypodermic needle and two microneedle arrays (36 needles of 180 and 280 mum height). The optimal method for microneedle application was determined in a pilot study. Pain intensity was scored using a visual analogue scale (VAS) and sensory perception determined using an adapted McGill Pain Questionnaire Short Form. Skin penetration was determined by external staining and measurement of trans-epidermal water loss (TEWL). Mean VAS scores, verbal descriptions and questionnaire responses showed that the 180 and 280 mum microneedles caused significantly less pain and discomforting sensation in participants than the hypodermic needle. Methylene blue staining and TEWL analysis confirmed that microchannels were formed in the skin following microneedle application. Evidence of microchannel repair and resealing was apparent at 8-24 h post-application. In summary, this study shows that pyramidal wet-etch microneedles can penetrate human skin with minimal pain and sensory discomfort, creating transient pathways for potential drug, vaccine and DNA delivery.

Psychosocial stress suppresses attractivity, proceptivity and pulsatile LH secretion in the ewe.

Various stressors suppress pulsatile secretion of luteinizing hormone (LH) in ewes and cortisol has been shown to be a mediator of this effect under various conditions. In contrast, little is known about the impact of stress and cortisol on sexual behavior in the ewe. Therefore, we tested the hypothesis that both psychosocial stress and stress-like levels of cortisol will reduce the level of attractivity, proceptivity and receptivity in addition to suppressing LH secretion in the ewe. In Experiment 1, a layered stress paradigm of psychosocial stress was used, consisting of isolation for 4 h with the addition of restraint, blindfold and noise of a barking dog (predator stress) at hourly intervals. This stress paradigm reduced LH pulse amplitude in ovariectomized ewes. In Experiment 2, ovariectomized ewes were artificially induced into estrus with progesterone and estradiol benzoate treatment and the layered stress paradigm was applied. LH was measured and sexual behavior was assessed using T-mazes and mating tests. Stress reduced pulsatile LH secretion, and also reduced attractivity and proceptivity of ewes but had no effect on receptivity. In Experiment 3, ewes artificially induced into estrus were infused with cortisol for 30 h. Cortisol elevated circulating plasma concentrations of cortisol, delayed the onset of estrus and resulted in increased circling behavior of ewes (i.e. moderate avoidance) during estrus and increased investigation and courtship from rams. There was no effect of cortisol on attractivity, proceptivity or receptivity during estrus. We conclude that psychosocial stress inhibits LH secretion, the ability of ewes to attract rams (attractivity) and the motivation of ewes to seek rams and initiate mating (proceptivity), but cortisol is unlikely to be the principal mediator of these effects.

Artificial lighting during winter increases milk yield in dairy ewes.

In Australia, the supply of sheep milk is reduced during the winter. Housing dairy animals under lights during winter is a simple technique to increase milk yield; however, it is difficult to predict the magnitude of this increase in dairy ewes, because there are few corroborating data. We studied 220 East Friesian crossbred ewes (50 primiparous and 170 multiparous ewes, respectively) that lambed in April to May 2007 (late autumn, southern hemisphere) and were weaned from their lambs within 24 h of parturition and milked exclusively by machine. These ewes were ranked according to their milk production, and ewes producing > or =1,000 mL/d of milk were allocated to 1 of 2 groups. One group of ewes was kept indoors under a long-day photoperiod (16 h of light), whereas the other group was kept indoors under a naturally declining day length. Ewes were maintained under these conditions for 8 wk. Milk yield was measured twice weekly, and ewe weight and condition were measured at weekly intervals. From a subset of ewes (n = 20 per group), milk samples were collected twice weekly at the morning milking to measure milk lipid, protein, and lactose, and blood samples were collected once a week to measure plasma prolactin concentrations. Mean daily milk yield was analyzed as a percentage of preexperimental milk yield because the milk yield of ewes housed under the long photoperiod was lower than that of ewes under a declining day length when the treatments began. Thus, the ewes under a long photoperiod yielded 91.7% of their starting yield by wk 8 of treatment, whereas ewes under a declining day length yielded 76.25% of their initial value (LSD = 5.1), and this divergence in milk yield was apparent by wk 2 of treatment. Mean plasma prolactin levels were greater in ewes housed under the long-day photoperiod (n = 20) compared with control ewes (n = 20) at wk 6 (168 +/- 27 vs. 72 +/- 19 ng/mL, respectively), wk 7 (125 +/- 28 vs. 37 +/- 7 ng/mL, respectively), and wk 8 of the experiment (132 +/- 35 vs. 31 +/- 7 ng/mL, respectively). The composition of the milk was similar between the groups at each time point, and milk from these ewes (n = 20 per group) contained, on average, 6.1 +/- 0.05% lipid, 4.8 +/- 0.02% protein, and 5.4 +/- 0.01% lactose (n = 309 samples). We concluded that ewes increase milk production in response to being housed under a long-day photoperiod during winter.

A comparison of the puncturing properties of gelatin and hypromellose capsules for use in dry powder inhalers.

This study investigates capsule puncture in dry powder inhalers. Gelatin and hydroxypropylmethyl cellulose (HPMC) capsules (stored at 11 and 33% relative humidities) were punctured using a pin from a Foradil inhaler, with insertion force measurement via an Instron tester. In HPMC capsules, the force after capsule puncture reduced by half and then increased to a second maximum as the pin shaft entered the hole. In gelatin capsules, the postpuncture force reduced to zero, indicating shell flaps losing contact with the pin. At lower moisture contents, both capsules were less flexible. This provides a tool to measure the shell properties of inhalation capsules.

Kisspeptin synchronizes preovulatory surges in cyclical ewes and causes ovulation in seasonally acyclic ewes.

We determined whether kisspeptin could be used to manipulate the gonadotropin axis and ovulation in sheep. First, a series of experiments was performed to determine the gonadotropic responses to different modes and doses of kisspeptin administration during the anestrous season using estradiol-treated ovariectomized ewes. We found that: 1) injections (iv) of doses as low as 6 nmol human C-terminal Kiss1 decapeptide elevate plasma LH and FSH levels, 2) murine C-terminal Kiss1 decapeptide was equipotent to human C-terminal Kiss1 decapeptide in terms of the release of LH or FSH, and 3) constant iv infusion of kisspeptin induced a sustained release of LH and FSH over a number of hours. During the breeding season and in progesterone-synchronized cyclical ewes, constant iv infusion of murine C-terminal Kiss1 decapeptide-10 (0.48 mumol/h over 8 h) was administered 30 h after withdrawal of a progesterone priming period, and surge responses in LH occurred within 2 h. Thus, the treatment synchronized preovulatory LH surges, whereas the surges in vehicle-infused controls were later and more widely dispersed. During the anestrous season, we conducted experiments to determine whether kisspeptin treatment could cause ovulation. Infusion (iv) of 12.4 nmol/h kisspeptin for either 30 or 48 h caused ovulation in more than 80% of kisspeptin-treated animals, whereas less than 20% of control animals ovulated. Our results indicate that systemic delivery of kisspeptin provides new strategies for the manipulation of the gonadotropin secretion and can cause ovulation in noncyclical females.

Predicting milk yield in sheep used for dairying in Australia.

It is necessary to identify traits that are simple to measure and correlated with milk yield to select ewes for dairying from existing populations of sheep in Australia. We studied 217 primiparous and 113 multiparous (second parity, n = 51; third parity, n = 40; and fourth parity, n = 22) East Friesian crossbred ewes, for 2 consecutive lactations, that were milked by machine following a period of suckling (24 to 28 d). We measured lamb growth, milk production, milk yield, and residual milk during early lactation (

Absence of Mycobacterium avium complex disease in patients with AIDS in Uganda.

The absence of disease due to Mycobacterium avium in Ugandan patients with AIDS, which we previously observed in a blood culture study, has been confirmed and our observations have been extended to 165 additional clinical isolates. Fourteen soil and water samples from the Ugandan environment have been cultured and revealed a high frequency of isolation of M. avium. The absence of M. avium complex disease in Uganda remains unexplained.

Quantitative sputum bacillary load during rifampin-containing short course chemotherapy in human immunodeficiency virus-infected and non-infected adults with pulmonary tuberculosis.

SETTING: National Tuberculosis (TB) Treatment Centre, Mulago Hospital and Joint Clinical Research Centre, Kampala, Uganda. OBJECTIVE: To compare the quantitative sputum bacillary load between TB patients infected with the human immunodeficiency virus (HIV) and those non-infected, during treatment with standard short course chemotherapy (SCC). DESIGN: To compare clinical characteristics and quantitative sputum bacillary load as measured by quantitative acid-fast bacilli (AFB) smears, colony forming unit (cfu) assay and time until positive culture in the BACTEC radiometric liquid system between 14 HIV-infected and 22 non-HIV-infected adults with initial episodes of smear-positive pulmonary TB at baseline and during treatment with standard four-drug SCC. RESULTS: Other than cavitation (P = 0.042) and adenopathy (P = 0.03), which were more common among non-HIV-infected and HIV-infected patients, respectively, there were no significant differences in baseline demographic, clinical, radiological and laboratory characteristics between the groups. Mean pretreatment sputum bacillary burden (6.5+/-0.51 log10 AFB/ml, 5.91+/-0.91 log10 cfu/ml and 1.8+/-1.7 days until positive BACTEC culture for HIV-infected patients and 6.32+/-0.85 log10 AFB/ml, 5.58+/-0.68 log10 cfu/ml and 1+/-1.2 days until positive BACTC culture for non-HIV-infected patients) were comparable between HIV-infected and non-HIV-infected patients. Clinical and bacteriological responses to standard SCC and treatment outcome did not differ between the groups. CONCLUSION: Quantitative sputum bacillary load at baseline and during SCC did not differ significantly between HIV-infected and non-HIV-infected adults with initial episodes of smear-positive TB.

Quantitative bacillary response to treatment in Mycobacterium tuberculosis infected and M. africanum infected adults with pulmonary tuberculosis.

Data regarding possible differences in microbiological response to therapy of disease caused by Mycobacterium tuberculosis and M. africanum are limited. Presenting clinical characteristics and sputum bacillary load during standard short-course chemotherapy in patients with newly-diagnosed pulmonary tuberculosis due to M. tuberculosis (n = 7) and M. africanum (n = 6) were compared. Changes in sputum bacillary load were measured using quantitative acid-fast bacilli smears, colony forming unit assay, and time until positive culture in the BACTEC radiometric system. Presentation and response to short course chemotherapy were comparable between patients infected with M. tuberculosis and those infected with M. africanum.

Lack of correlation between nasal cultures positive for Staphylococcus aureus and the development of S. aureus exit-site infections: results unaffected by routine mupirocin treatment of nasal S. aureus carriage.

Whether nasal carriage of Staphylococcus aureus is associated with an increased risk of S. aureus exit-site infection remains controversial. We performed nasal cultures prior to peritoneal dialysis catheter placement in all of our patients beginning in September 1990. We also performed nasal cultures on a cohort of patients already on peritoneal dialysis. Patients with positive cultures received a prescription for a ten-day course of intranasal mupirocin. Exit-site and nasal cultures were performed on every subsequent office visit until the end of the study in April 1993. The initial visit and three widely-spaced subsequent visits were chosen for data analysis. There were 68 patients entered into the study. Data from a total of 272 visits were analyzed. The patients ranged in age from 18-80 years. There were 27 diabetics. We found no correlation between initial positive nasal cultures and the subsequent development of a S. aureus exit-site infection. All identified nasal carriers were treated with mupirocin. However, the subsequent development of a S. aureus exit-site infection could not be correlated to a prior S. aureus carrier state or lack thereof.

Postmortem diagnosis of meningococcemia by detection of capsular polysaccharides.

Detection of specific meningococcal capsular polysaccharide (CPS) in postmortem blood permits rapid diagnosis of meningococcemia and differentiation from pneumococcemia and septicemia caused by Haemophilus influenzae Type b. We present studies validating application of latex agglutination assay for CPS on blood samples collected at autopsy, delineate the circumstances when CPS testing is indicated, and illustrate the usefulness of this procedure by several recent cases. Blood samples from victims dying of injury or disease other than infection were examined to determine whether the postmortem interval, bacterial contamination, anticoagulants, or delay in testing would result in false positive assays. Series 1 samples, collected so as to minimize bacterial contamination, were immediately submitted for assay. Series 2 evaluated the effect of adverse conditions of collection, anticoagulation, and prolonged sample storage. Despite extended postmortem intervals of up to 14 days, heavy bacterial contamination, prolonged storage at 4 degrees C, deep hemolysis, and presence of anticoagulants, false positive assays were seldom observed.

Waste management models and their application to sustainable waste management.

The purpose of this paper is to review the types of models that are currently being used in the area of municipal waste management and to highlight some major shortcomings of these models. Most of the municipal waste models identified in the literature are decision support models and for the purposes of this research, are divided into three categories-those based on cost benefit analysis, those based on life cycle assessment and those based on multicriteria decision making. Shortcomings of current waste management models include that they are concerned with refinements of the evaluation steps (e.g. stage four of AHP or the improvement of weight allocations in ELECTRE) rather than addressing the decision making process itself. In addition, while many models recognise that for a waste management model to be sustainable, it must consider environmental, economic and social aspects, no model examined considered all three aspects together in the application of the model.

Determination of drug susceptibility and DNA fingerprint patterns of clinical isolates of Mycobacterium tuberculosis from Kampala, Uganda.

OBJECTIVE: To ascertain the rate of initial drug resistance and transmission patterns of Mycobacterium tuberculosis in Kampala, Uganda. SETTING: National Tuberculosis (TB) Treatment Centre, Mulago Hospital, Kampala, Uganda and Case Western Reserve University, Cleveland, Ohio, USA and McClellan Memorial Veterans Hospital, Little Rock, Arkansas, USA. METHODS: Using a radiometric BACTEC 460 TB system, susceptibility of 215 M. tuberculosis isolates from previously untreated patients from Kampala, Uganda (age range, 17-48 years, mean, 28 years; 56% males and 69% human immunodeficiency virus (HIV)-seropositive) was determined for isoniazid, rifampin, streptomycin and ethambutol. Isolates from 73 patients, selected on the basis of geographical location, were tested for strain diversity or relatedness using the IS6110 DNA fingerprinting technique. RESULTS: Resistance rates were as follows: isoniazid, 7.9% streptomycin, 6.1% rifampin, 1.4% and ethambutol 0.9%. Twelve per cent of the strains were resistant to at least one of the first line drugs tested and 4.7% were multiply resistant. There were no significant differences in resistance rates between patients with and without HIV infection. Using the number and size of DNA fragments containing IS6110, only three clusters of isolates with identical RFLP patterns were found out of the 73 isolates tested (8.2%). Each cluster contained two isolates. Three (4.1%) isolates had less than seven copies of IS6110. CONCLUSION: This study shows that in Uganda initial drug resistance rates to anti-tuberculosis agents are low and similar to other sub-Saharan African countries and that multiple strains of M. tuberculosis have been transmitted within the community.

PIP: This study was undertaken to determine the rate of initial drug resistance and transmission patterns of Mycobacterium tuberculosis (TB) in Kampala, Uganda. Using a radiometric BACTEC 460 TB system, 215 M. tuberculosis isolates from previously untreated patients (aged 17-48 years, mean age = 28 years; 56% males and 69% HIV-seropositive) were analyzed for susceptibility to isoniazid, rifampin, streptomycin, and ethambutol. Isolates from 73 patients were examined for strain diversity or relatedness using the insertional sequence 6110 (IS6110) DNA fingerprinting technique. The study revealed the following drug resistance rates: isoniazid, 7.9%; streptomycin, 6.1%; rifampin, 1.4%; and ethambutol, 0.9%. Resistance to at least one of the first line drugs tested were developed by 12% of the strains, while 4.7% showed multiple resistance. However, no significant differences in resistance rates were found between patients with and without HIV infection. Using the number and size of DNA fragments containing IS6110, only three clusters of isolates with identical patterns were found out of the 73 isolates tested (8.2%). Each cluster contained two isolates, and three isolates had less than 7 copies of IS6110. These findings suggest that initial drug resistance to anti-tuberculosis agents in this region is low and similar to other countries in sub-Saharan Africa and that multiple strains of M. tuberculosis have been transmitted within the community.

Development of a decision-support tool for identifying the most suitable approach to achieve nitrate source determination.

Numerous approaches have been suggested for differentiating point and diffuse sources of nitrate contamination, including nitrate stable isotopes, microbiological analyses, genetic markers and chemical markers. Each approach has its own strengths and limitations. As a result, the most appropriate approach to use largely depends upon the scenario and the context of the study. However, available data on nitrate source determination is highly fragmented and approach dependent, with very little if any interface between the different techniques. This makes it difficult for stakeholders to identify the most suitable approach to adopt in a specific scenario. Therefore, this paper examines the development and application of a decision-support tool to support environmental forensics studies for nitrate contamination. In particular, this tool can support policy makers, regulators and operators within the field in understanding the environmental hazards and processes resulting from nitrate contamination, and to implement appropriate actions for limiting the impacts that may arise from such contamination. The tool was developed using the IDEF0 modeling system, and evaluated by interviewing key stakeholders who suggested a number of important implications for practice.

Transfer of the virulence-associated protein a-bearing plasmid between field strains of virulent and avirulent Rhodococcus equi.

BACKGROUND: Virulent and avirulent isolates of Rhodococcus equi coexist in equine feces and the environment and are a source of infection for foals. The extent to which plasmid transfer occurs among field strains is ill-defined and this information is important for understanding the epidemiology of R. equi infections of foals. OBJECTIVES: To estimate the frequency of transfer of the virulence plasmid between virulent and avirulent strains of R. equi derived from foals and their environment. ANIMALS: None. METHODS: In vitro study; 5 rifampin-susceptible, virulent R. equi isolates obtained from clinically affected foals or air samples from a farm with a history of recurrent R. equi foal pneumonia were each mixed with 5 rifampin-resistant, avirulent isolates derived from soil samples, using solid medium, at a ratio of 10 donor cells (virulent) per recipient cell. Presumed transconjugates were detected by plating on media with rifampin and colony immunoblotting to detect the presence of the virulence-associated protein A. RESULTS: Three presumed transconjugates were detected among 2,037 recipient colonies, indicating an overall estimated transfer frequency of 0.15% (95% CI, 0.03­0.43%). All 3 transconjugates were associated with a single donor and 2 recipient strains. Genotyping and multiplex PCR of presumed transconjugates demonstrated transfer of the virulence-associated protein A-bearing plasmid between virulent and avirulent R. equi. CONCLUSIONS AND CLINICAL IMPORTANCE: Transfer of the virulence plasmid occurs with relatively high frequency. These findings could impact strategies to control or prevent R. equi through environmental management.

The potential for a suite of isotope and chemical markers to differentiate sources of nitrate contamination: a review.

Nitrate is naturally found within the environment as part of the nitrogen cycle. However, anthropogenic inputs have greatly increased nitrate loads within ground and surface waters. This has had a severe impact on aquatic ecosystems and has given rise to health considerations in humans and livestock. Therefore, the identification of nitrate sources is important in preserving water quality and achieving sustainability of our water resources. Nitrate sources can be determined based on the nitrate nitrogen (N) and oxygen (O) isotopic compositions (δ(15)N, δ(18)O). However, sewage and manure have overlapping δ(15)N and δ(18)O values making their differentiation on this basis problematic. The specific differentiation between sources of faecal contamination is of particular importance, because the risk to humans is usually considered higher from human faecal contamination (sewage) than from animal faecal contamination. This review summarises the current state of knowledge in using isotope tracers to differentiate various nitrate sources and identifies potential chemical tracers for differentiating sewage and manure. In particular, an in depth review of the current state of knowledge regarding the necessary considerations in using chemical markers, such as pharmaceuticals and food additives, to differentiate sewage and manure sources of nitrate contamination will be given, through an understanding of their use, occurrence and fate, in order to identify the most suitable potential chemical markers.