Comparative efficacy of stannous fluoride and copper sulfate footbath solutions for the treatment and prevention of digital dermatitis in lactating dairy cows.

The objective of this study was to determine whether a novel footbath solution containing stannous fluoride (SnF2) was superior to 5% copper sulfate solution for the treatment and prevention of digital dermatitis (DD) in dairy cattle. Study 1 was conducted over 4 weeks in Missouri and involved 34 lactating Holstein-Friesian cows with hind feet DD lesions. Cows in group SF walked through a footbath containing a proprietary formulation of SnF2 once weekly, whereas cows in group CS walked through a 5% CuSO4 footbath once daily for 5 d each week. Study 2 was conducted over 8 weeks in California and involved 40 lactating Holstein-Friesian cows with hind feet DD lesions. Cows in group SF walked through a SnF2 footbath for 3 consecutive days then once a week for the following 7 weeks. Cows in group CS walked through a 5% CuSO4 footbath 3 times each week for 8 weeks. Data collection included lesion type, lesion area, locomotion score, and pain score. Digital dermatitis was actively transmitted in study 1, and lesion area and locomotion scores were lower in group SF than group CS. In contrast, DD was not actively transmitted in study 2, and lesion area and locomotion scores were similar in groups SF and CS. Stannous fluoride delayed the development of active DD lesions in study 1 compared with copper sulfate, with a lower relative risk (0.57, P < 0.001) of a hind foot developing an active DD lesion over 28 d. However, SnF2 decreased the rate that active DD lesions transitioned to M3, M4, or M0 lesions compared with 5% copper sulfate in both studies, with the relative risk of a hind foot with an active DD lesion transitioning to M3, M4, or M0 in group SF being slightly lower in study 1 (0.83, P = 0.042) and study 2 (0.90, P = 0.020) than group CS. Our findings demonstrated that walking cows through a stannous fluoride footbath once per week in a herd undergoing active transmission of infection was more effective in preventing active DD lesions, but less effective in treating active DD lesions, than walking cows through a copper sulfate footbath 4 times per week. The novel SnF2 footbath solution shows promise for controlling DD in dairy herds that want an alternative footbath solution to CuSO4 and are interested in limiting the environmental accumulation of copper.

Brain-inspired computing needs a master plan.

New computing technologies inspired by the brain promise fundamentally different ways to process information with extreme energy efficiency and the ability to handle the avalanche of unstructured and noisy data that we are generating at an ever-increasing rate. To realize this promise requires a brave and coordinated plan to bring together disparate research communities and to provide them with the funding, focus and support needed. We have done this in the past with digital technologies; we are in the process of doing it with quantum technologies; can we now do it for brain-inspired computing?

Committee machines-a universal method to deal with non-idealities in memristor-based neural networks.

Artificial neural networks are notoriously power- and time-consuming when implemented on conventional von Neumann computing systems. Consequently, recent years have seen an emergence of research in machine learning hardware that strives to bring memory and computing closer together. A popular approach is to realise artificial neural networks in hardware by implementing their synaptic weights using memristive devices. However, various device- and system-level non-idealities usually prevent these physical implementations from achieving high inference accuracy. We suggest applying a well-known concept in computer science-committee machines-in the context of memristor-based neural networks. Using simulations and experimental data from three different types of memristive devices, we show that committee machines employing ensemble averaging can successfully increase inference accuracy in physically implemented neural networks that suffer from faulty devices, device-to-device variability, random telegraph noise and line resistance. Importantly, we demonstrate that the accuracy can be improved even without increasing the total number of memristors.

Changes in the metabolic profiles of dairy cows before and after calving that were mainly fed fodder beet (Beta vulgaris vulgaris L.) during the dry period.

Case history: Two commercial pasture-based farms within the North Canterbury district of New Zealand were feeding fodder beet (Beta vulgaris vulgaris L.) as a large proportion of the diet to cows during the dry period. On each farm 25 multiparous cows were blood sampled up to six times from 28 days before, to 21 days after calving (Day 0). Plasma samples were analysed for concentrations of ß-hydroxybutyrate (BHBA), non-esterified fatty acid (NEFA), Ca, Mg and P, and aspartate aminotransferase (AST) activity. The first sampling visit was performed when cows were being fed their maximum intake of fodder beet. Clinical findings: The mean body condition score (BCS) of cows on Farm 1 was 5.4 (95% CI = 5.3-5.6) and on Farm 2, 5.4 (95% CI = 5.3-5.6) at first sampling. Mean concentrations of BHBA increased between Days -15 and Day -8 then decreased postpartum on Day 2 before increasing again on Day 21. On Farm 2, concentrations remained low (<1.2 mmol/L) on all days of sampling. Mean concentrations of NEFA in plasma remained low during the periparturient period on Farm 1, then increased on Day 2. On Farm 2, concentrations were elevated above 0.3 mmol/L between Days -28 and -17 then decreased on Day -10, before increasing on Day 2. Mean concentrations of Ca, Mg and P were higher than threshold values on both farms prepartum. However on Day 2, there were 8/23 (35%) cows on Farm 1 and 6/23 (26%) cows on Farm 2 with concentrations of Ca in plasma <2.0 mmol/L, and 10/23 (44%) cows on Farm 1 and 8/23 (35%) cows on Farm 2 with concentrations of P in plasma <1.3 mmol/L. Mean AST activities remained relatively constant and below 130 IU/L on both farms at all sampling times. Clinical relevance: On both farms, post-partum hypocalcaemia and hypophosphataemia were common after calving despite differing fodder beet feeding and mineral supplementation regimes. There was more variation in energy status, especially prior to calving. More research is required on factors affecting mineral and energy status in dry cows fed fodder beet.

Preliminary investigation of the effect of treating sheep during pregnancy with a vitamin A, D, E formulation on the incidence of vaginal prolapse.

Aim: To determine if vitamin D3 treatment reduced the incidence of vaginal prolapse in pregnant sheep on a North Canterbury sheep breeding property.Methods: Pregnant ewes from a single farm were allocated to three treatment groups in May 2018. At this time, the first group (EarlyVitADE; n = 512) received an I/M 1 mL dose of 500,000 IU/mL vitamin D3, 60,000 IU/mL vitamin A, and 25 mg/mL vitamin E. This was repeated in July 2018, when the second group (LateVitADE; n = 695) also received the same treatment. The third group (n = 737) were untreated controls. All cases of vaginal prolapse on the property were recorded from pregnancy diagnosis in June 2018 until ewes were set-stocked in August 2018. The planned start of lambing was 10 August 2018.Results: During the period of observation, vaginal prolapses were recorded in 3/699 (0.4%) 2-year-old ewes, and the odds of vaginal prolapse were not associated with treatment group in these ewes (p > 0.3). Amongst ewes aged ≥3 years, during the same period, there were 6/333 (1.8%), 6/443 (1.4%) and 25/469 (5.3%) cases in the EarlyVitADE, LateVitADE and control groups, respectively. Compared to control ewes, the odds of vaginal prolapse were reduced in both the EarlyVitADE (OR = 0.37; 95% CI = 0.15-0.92) and LateVitADE (OR = 0.25; 95% CI = 0.10-0.62) treatment groups.Conclusions and clinical relevance: In this preliminary study, administration of injectable vitamins A, D3, and E to pregnant ewes reduced the incidence of vaginal prolapse during the period from pregnancy diagnosis to set-stocking on one North Canterbury hill-country farm. Due to the restricted data collection period, this investigation should be replicated to better quantify the repeatability of the observed treatment effect over the complete lambing period.

Intrinsic Resistance Switching in Amorphous Silicon Suboxides: The Role of Columnar Microstructure.

We studied intrinsic resistance switching behaviour in sputter-deposited amorphous silicon suboxide (a-SiO x ) films with varying degrees of roughness at the oxide-electrode interface. By combining electrical probing measurements, atomic force microscopy (AFM), and scanning transmission electron microscopy (STEM), we observe that devices with rougher oxide-electrode interfaces exhibit lower electroforming voltages and more reliable switching behaviour. We show that rougher interfaces are consistent with enhanced columnar microstructure in the oxide layer. Our results suggest that columnar microstructure in the oxide will be a key factor to consider for the optimization of future SiOx-based resistance random access memory.

X-ray spectromicroscopy investigation of soft and hard breakdown in RRAM devices.

Resistive random access memory (RRAM) is considered an attractive candidate for next generation memory devices due to its competitive scalability, low-power operation and high switching speed. The technology however, still faces several challenges that overall prohibit its industrial translation, such as low yields, large switching variability and ultimately hard breakdown due to long-term operation or high-voltage biasing. The latter issue is of particular interest, because it ultimately leads to device failure. In this work, we have investigated the physicochemical changes that occur within RRAM devices as a consequence of soft and hard breakdown by combining full-field transmission x-ray microscopy with soft x-ray spectroscopic analysis performed on lamella samples. The high lateral resolution of this technique (down to 25 nm) allows the investigation of localized nanometric areas underneath permanent damage of the metal top electrode. Results show that devices after hard breakdown present discontinuity in the active layer, Pt inclusions and the formation of crystalline phases such as rutile, which indicates that the temperature increased locally up to 1000 K.

Resynchronising returns to service in anoestrous dairy cows in the South Island of New Zealand.

AIMS: To investigate the effect of targeted resynchronisation of cows treated for non-observed oestrus before the planned start of mating (PSM), that were not detected in oestrus or pregnant 23 days after treatment (phantom cows), on the proportion pregnant at 42 days after PSM and the end of mating. METHODS: Farm staff from eight herds in two regions of the South Island of New Zealand identified 1,819 cows not showing oestrus by 10 days before PSM. These cows were treated with intravaginal progesterone for 7 days, and I/M gonadorelin 10 days and 1 day before PSM. Three days before PSM they were injected with cloprostenol and equine chorionic gonadotrophin, with fixed time artificial insemination (FTAI) at PSM. By 23 days after PSM, 1,218 cows had not returned to oestrus. Of these, 161 cows confirmed not pregnant by transrectal ultrasonography were randomly assigned to no treatment (control group; n=74) or were resynchronised 25 days after PSM using the same treatment programme as above, with FTAI 35 days after PSM (n=87). All cows that returned to oestrus were artificially inseminated until 42 days after PSM, when natural mating was used. All cows were examined using transrectal ultrasonography 80 to 90 days after PSM to confirm conception dates. RESULTS: Of the 1,819 anoestrous cows treated before PSM, 526 (29 (95% CI=23.1-34.0)%) had not been observed in oestrus by 23 days after PSM and had not conceived, so were diagnosed as phantoms cows. For resynchronised cows, 42/87 (48 (95% CI=37.8-58.8)%) were pregnant by 42 days after PSM compared to 21/74 (28 (95% CI=18.1-38.7)%) control cows (p=0.009). At the end of mating 58/87 (67 (95% CI=56.6-76.7)%) cows in the resynchronised group were pregnant and 46/74 (62 (95% CI=50.9-73.2)%) in the control group (p=0.554). The hazard of conception from 21 to 42 days after PSM was 1.9 (95% CI=1.07-3.12) times greater for resynchronised than control cows (p=0.026). CONCLUSION: In cows not observed in oestrus and treated before PSM, resynchronisation increased the proportion pregnant by 42 days after PSM. CLINICAL RELEVANCE: The benefit of resynchronisation depends on the number of anoestrous cows before PSM and the number of phantom cows after PSM. However at the herd-level it is likely that providing advice to reduce the known risk factors for cows not being observed in oestrus before the PSM may well be more cost effective than identifying and treating a sub-population of phantom cows.

Transitions Study of predictors of illness progression in young people with mental ill health: study methodology.

AIM: An estimated 75% of mental disorders begin before the age of 24 and approximately 25% of 13-24-year-olds are affected by mental disorders at any one time. To better understand and ideally prevent the onset of post-pubertal mental disorders, a clinical staging model has been proposed that provides a longitudinal perspective of illness development. This heuristic model takes account of the differential effects of both genetic and environmental risk factors, as well as markers relevant to the stage of illness, course or prognosis. The aim of the Transitions Study is to test empirically the assumptions that underpin the clinical staging model. Additionally, it will permit investigation of a range of psychological, social and genetic markers in terms of their capacity to define current clinical stage or predict transition from less severe or enduring to more severe and persistent stages of mental disorder. METHOD: This paper describes the study methodology, which involves a longitudinal cohort design implemented within four headspace youth mental health services in Australia. Participants are young people aged 12-25 years who have sought help at headspace and consented to complete a comprehensive assessment of clinical state and psychosocial risk factors. A total of 802 young people (66% female) completed baseline assessments. Annual follow-up assessments have commenced. CONCLUSIONS: The results of this study may have implications for the way mental disorders are diagnosed and treated, and progress our understanding of the pathophysiologies of complex mental disorders by identifying genetic or psychosocial markers of illness stage or progression.

The interaction of gold and silver nanoparticles with a range of anionic and cationic dyes.

We describe the synthesis of charge-stabilised gold and silver nanoparticles by a modified Turkevich method and their interaction with a selection of cationic and anionic dyes. It was found that gold nanoparticles interact strongly with cationic dyes and in some cases enhanced absorption was observed by UV-visible spectroscopy. It is also shown that addition of cationic dyes to gold nanoparticles triggers aggregation of the nanoparticles into large, micrometre-scale clusters. Simultaneous fragmentation and agglomeration of the gold nanoparticles was observed at high concentrations of cationic dye in the solution. These effects were not observed when gold nanoparticles were mixed with anionic dyes, nor for silver nanoparticles with either cationic or anionic dyes.

Comparison between low-dose, high-sort and high-dose, low-sort semen on conception and calf sex ratio in Jersey heifers and cows.

The objective of this clinical trial was to compare conception and newborn calf sex ratios among Jersey heifers and lactating cows inseminated with either standard sex-sorted semen (low-dose, high-sort; LDHS) containing 2.1 × 10(6) sorted sperm at 90% purity or high-dose, low-sort (HDLS) semen containing 10 × 10(6) sorted sperm at 75% purity. After a specified voluntary waiting period (VWP), female subjects, consisting of nulliparous heifers (VWP 10 mo of age) and lactating cows (VWP 50d in milk), received their first service and were systematically allocated to each treatment group in the order in which they presented for artificial insemination (AI). Females were bred to the same sire and type of sex-sorted semen for up to 2 additional services. Animals that were not pregnant after 3 breeding attempts were excluded. A total of 1,846 services were performed on 1,011 eligible females (LDHS; n=494, HDLS; n=517), which consisted of 516 nulliparous heifers and 495 lactating cows. Study groups were comparable with respect to the mean age at first AI for nulliparous heifers and the mean days in milk at first AI for parous cows. Insemination with HDLS semen did not result in a higher proportion of pregnancies per AI (P/AI) compared with LDHS semen for either nulliparous heifers (P/AI=43 vs. 38%) or parous cows (P/AI=47 vs. 43%). Insemination of nulliparous heifers using HDLS resulted in a lower proportion of newborn female calves compared with those bred to LDHS (76% vs. 87%). Similarly, lactating cows bred to HDLS gave birth to a lower proportion of newborn female calves compared with those bred to LDHS (79 vs. 90%). The odds ratio for a female calf to be born to an animal inseminated with HDLS compared with LDHS was 0.32 for nulliparous heifers and 0.19 for parous cows. Overall, the use of HDLS resulted in fewer females compared with LDHS, which may be explained by the lower concentration of X-bearing spermatozoa in HDLS compared with LDHS.

Quantum conductance in silicon oxide resistive memory devices.

Resistive switching offers a promising route to universal electronic memory, potentially replacing current technologies that are approaching their fundamental limits. In many cases switching originates from the reversible formation and dissolution of nanometre-scale conductive filaments, which constrain the motion of electrons, leading to the quantisation of device conductance into multiples of the fundamental unit of conductance, G0. Such quantum effects appear when the constriction diameter approaches the Fermi wavelength of the electron in the medium - typically several nanometres. Here we find that the conductance of silicon-rich silica (SiOx) resistive switches is quantised in half-integer multiples of G0. In contrast to other resistive switching systems this quantisation is intrinsic to SiOx, and is not due to drift of metallic ions. Half-integer quantisation is explained in terms of the filament structure and formation mechanism, which allows us to distinguish between systems that exhibit integer and half-integer quantisation.

Minimal progesterone concentration required for embryo survival after embryo transfer in lactating Holstein cows.

Objectives were to determine progesterone concentration (P4) from days 4 to 28 relative to presumptive estrus necessary for maintenance of pregnancy in lactating Holstein cows. Cows were assigned to the low P4 (LowP4, n=28) or control (n=153) treatments. All cows were presynchronized with two injections of PGF(2α) (14d apart) and an ovulation synchronization protocol (11d later; GnRH on day -10, PGF(2α) on day -3; and GnRH on day 0=presumptive estrus). Cows in the Low P4 treatment received 2 injections of prostaglandin F(2α) on days 4 and 5 (day 0=presumptive estrus) and a new CIDR insert on day 5 that was replaced every 7d until day 28. Blood was sampled on days -9, -2, 0, 4, 7,14, 21, and 28. Ovaries were examined with ultrasound on days -9, -3, and 7 and cows bearing a corpus luteum ≥20mm on day 7 received an embryo. On days 0, 4 and 7 P4 did not differ (P≥0.27) but control cows had greater (P<0.01) P4 on days 14, 21, and 28. Progesterone concentration fold change from day 0 to 7 was not (P=0.14) affected by treatment, but P4 concentration fold change from day 7 to 14 was (P<0.01) greater for control cows compared with LowP4 cows. No LowP4 cows became pregnant after embryo transfer, whereas 35.7, 25.5, and 21.4% of control cows were pregnant on day 28, 42, and 63, respectively. Progesterone concentration fold changes from day 0 to 7 (P=0.03) and from day 7 to 14 (P=0.05) were associated with pregnancy outcomes on day 63. Among cows that were pregnant on day 63, the minimum P4 concentration fold changes from day 0 to 7 and from day 7 to 14 were 2.71 and 1.48, respectively. Interestingly, cows with P4 concentration <5ng/mL on day 14 were (P=0.01) and tended to be (P=0.07) more likely to lose pregnancy from day 28 to 42 and from day 28 and 63, respectively. Faster rise in P4 concentration during the metestrus and early diestrus are associated with pregnancy establishment following embryo transfer, which suggests that early rise in P4 concentration has an indirect effect on embryo development through modulation of uterine environment and secretion of histotroph. Furthermore, the positive effects of early rise in P4 concentration appear to go beyond the phase of maternal recognition of pregnancy through adhesion and placentation stages.

Investigation of quartz grain surface textures by atomic force microscopy for forensic analysis.

This paper presents a study of quartz sand grain surface textures using atomic force microscopy (AFM) to image the surface. Until now scanning electron microscopy (SEM) has provided the primary technique used in the forensic surface texture analysis of quartz sand grains as a means of establishing the provenance of the grains for forensic reconstructions. The ability to independently corroborate the grain type classifications is desirable and provides additional weight to the findings of SEM analysis of the textures of quartz grains identified in forensic soil/sediment samples. AFM offers a quantitative means of analysis that complements SEM examination, and is a non-destructive technique that requires no sample preparation prior to scanning. It therefore has great potential to be used for forensic analysis where sample preservation is highly valuable. By taking quantitative topography scans, it is possible to produce 3D representations of microscopic surface textures and diagnostic features for examination. Furthermore, various empirical measures can be obtained from analysing the topography scans, including arithmetic average roughness, root-mean-square surface roughness, skewness, kurtosis, and multiple gaussian fits to height distributions. These empirical measures, combined with qualitative examination of the surfaces can help to discriminate between grain types and provide independent analysis that can corroborate the morphological grain typing based on the surface textures assigned using SEM. Furthermore, the findings from this study also demonstrate that quartz sand grain surfaces exhibit a statistically self-similar fractal nature that remains unchanged across scales. This indicates the potential for a further quantitative measure that could be utilised in the discrimination of quartz grains based on their provenance for forensic investigations.

Myth: tocolysis for prevention of preterm birth has a major role in modern obstetrics.

Tocolytics are widely used to reduce uterine activity in the context of preterm labour. Growing evidence that bacterial colonization of fetal membranes and amniotic fluid triggers an inflammatory response in mother and fetus and leads to preterm labour and long term neurological and respiratory complications in the neonate also raises questions about the desirability of prolonging pregnancy in this context. Combined with recent meta-analyses that fail to demonstrate improvements in neonatal outcome with tocolytic use, and a poor maternal/fetal side-effect profile, the case for continued use of these drugs needs to be questioned.

The disposition and metabolism of zibotentan (ZD4054): an oral-specific endothelin A receptor antagonist in mice, rats and dogs.

Zibotentan (ZD4054) is an oral-specific endothelin A receptor antagonist in development for the treatment of castration-resistant prostate cancer. In a number of preclinical studies, the disposition and metabolism of zibotentan were investigated in mice, rats and dogs. Following oral and intravenous administration, zibotentan was slowly absorbed (maximal concentration at approximately 4 h) and rapidly excreted, with the majority being eliminated by 48 h. The main route of elimination was via the urine in dogs and female rats, but via the faeces in male rats and mice of both sexes. Zibotentan was moderately bound to plasma proteins of all species examined (55-95%), and widely distributed throughout all tissues with the highest concentrations seen in the organs of excretion. Zibotentan was moderately metabolised. Zibotentan was well absorbed, moderately bound to plasma proteins, widely distributed and excreted predominantly via the urine.

Towards population inversion of electrically pumped Er ions sensitized by Si nanoclusters.

This study reports the estimation of the inverted Er fraction in a system of Er doped silicon oxide sensitized by Si nanoclusters, made by magnetron sputtering. Electroluminescence was obtained from the sensitized erbium, with a power efficiency of 10(-2)%. By estimating the density of Er ions that are in the first excited state, we find that up to 20% of the total Er concentration is inverted in the best device, which is one order of magnitude higher than that achieved by optical pumping of similar materials.

Pruritus in pregnancy: a study of anatomical distribution and prevalence in relation to the development of obstetric cholestasis.

The main objective of this study was to determine the prevalence and anatomical distribution of pruritus in 6532 pregnant women from a UK antenatal population. Pregnant women attending and completing antenatal care at two general hospitals over a 12-month period were recruited and contacted on three occasions by post. Medical advice and a questionnaire detailing the nature and severity of their pruritus were included. Pruritus in pregnancy, as reported by questionnaire, affected approximately 23% of pregnancies (n = 1521/6532 women) and 1.6% (n = 25) of these women developed obstetric cholestasis (OC). Overall, 0.66% of the antenatal population (43/6532) had a clinical diagnosis of OC (95% CI: 0.48-0.89%). Itching unrelated to OC was most commonly reported to be worst on the abdomen (31%, 616/2014). Women with OC reported pruritus to be most severe on the palms and soles in 16% (4/25) and 'all over' in 24% (6/25) compared with 5% (54/1120) (P < 0.05) and 4% (42/1120, P < 0.0001) of those without OC. In conclusion, pruritus affected approximately one in four women and OC one in 135 women during the study period. Women whose pruritus is 'all over' or most severe on the 'palms or soles' may be at greater risk of the disease.

Fetal fibronectin as a predictor of spontaneous preterm labour in asymptomatic women with a cervical cerclage.

OBJECTIVE: To assess the accuracy of fetal fibronectin (fFN) testing for prediction of preterm labour in asymptomatic high-risk women with a cervical cerclage. DESIGN: Retrospective observational study. SETTING: United Kingdom. POPULATION: Nine hundred and ten asymptomatic women at high-risk of Preterm birth referred to specialist antenatal clinics and undergoing fFN testing between November 1997 and December 2007. METHODS: Women had fFN tests taken between 23(+0) and 27(+6) weeks' gestation, on one or more occasions. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive values and negative predictive values of fFN testing for predicting delivery <30 and <37 weeks were compared in those with and without cerclage. RESULTS: For delivery <30 weeks' gestation, the specificity of fFN testing was significantly lower in women with cervical cerclage (77% vs 90%; P < or = 0.00001). The sensitivity of the test was similar between the groups (78.6 (no-cerclage) vs 60% (cerclage); P > 0.4). The negative predictive value of the fFN test for delivery <30 weeks was high in both groups (>98%). CONCLUSIONS: Asymptomatic high-risk women with cerclage in situ are more likely to have a false positive fFN test. The negative predictive value is similar.

Evaluation of the use of UPLC-TOFMS with simultaneous [14C]-radioflow detection for drug metabolite profiling: application to propranolol metabolites in rat urine.

The non-selective beta-adrenergic receptor antagonist propranolol [1-(isopropylamino)-3-(1-naphthoxy)-2-propanol] is metabolised extensively in vivo. Enumerating and identifying the many metabolites that result from multiple biotransformations provides a considerable analytical challenge, greatly aided by efficient chromatography coupled to sensitive mass spectrometric detection. Here the use of the newly introduced high-resolution technique of "ultra performance liquid chromatography" (UPLC) linked to quadrupole time-of-flight mass spectrometry (TOFMS) with simultaneous [(14)C]-radioflow detection was applied to rapid metabolite profiling. [14C]-propranolol, dosed intraperitoneally to rat at 25 mg kg(-1) and 200 microCi kg(-1) was used as a model compound for this evaluation. Some 14 metabolites were detected in the urine by this technique including a number of conjugated metabolites such as sulphates, several isobaric glucuronides and two novel di-glucuronides.