Molecular confirmation of Sarcocystis fayeri in a donkey

Sarcocystis fayeri is a canine protozoan parasite with an equine intermediate host. Historically classified as an incidental pathogen, recent literature has described the toxic effects of Sarcocystis fayeri in human food poisoning, and highlighted potential involvement in equine neuromuscular disease. Until now, horses were believed to be the exclusive intermediate host. This study reports the first molecular confirmation of S. fayeri in a donkey, and gives rise to the consideration of donkeys being a potential reservoir for the parasite. This finding is of particular importance in understanding the epidemiology of this disease

Stable isotope tracer studies for the measurement of equine gastrointestinal motility

Abdominal disorders are a major cause of morbidity and mortality in horses, and abnormal gastrointestinal motility may be a significant factor in the aetiopathogenesis of many equine colic syndromes. The understanding of such conditions is hampered by the lack of suitable noninvasive tests for the quantitative measurement of intestinal transit. The overall objective of this work was to investigate the potential value of stable 13C-isotope breath tests for the assessment of specific parameters of equine gastrointestinal motility. A new method developed for the collection of equine expiratory breath and measurement of its ratio was shown to have excellent repeatability. Assessment of peripheral blood tracer content was also performed and correlated significantly to that of concurrent breath samples. In the first study, the 13C-octanoic acid breath test (13C-OABT) was evaluated for the measurement of solid phase gastric emptying rate in 12 healthy horses by direct comparison with the predicate method of gastric scintigraphy. Having shown that the 13C-OABT was a reliable diagnostic procedure for use in healthy horses, a further study was performed against scintigraphy in subjects with atropine-induced gastroparesis (n = 8) to determine whether the test remained accurate when emptying rate was markedly prolonged. In study 3, the 13C-OABT was applied to measure the relative and dose-related effects of common sedative agents on solid phase gastric emptying in 8 horses. The study results may have clinical significance for case selection when these agents are used for purposes of sedation and/or analgesia. The 13C-bicarbonate and sodium 13C-acetate breath tests were investigated in study 4 for the assessment of equine liquid phase gastric emptying, and elucidation of the pattern of 13CO2 recovery from the body bicarbonate pool. The lactose 13C-ureide breath test (13C-LUBT) was investigated in study 5 for estimation of orocaecal transit time (OCTT), and concurrent comparison made to the hydrogen breath test (H2BT). In study 6 the induced 13C-LUBT was evaluated in vivo for the measurement of OCTT and a mean (+/- s.d.) time of 3.24 (+/- 0.65) h was gained. In order to examine the relationship between gastric emptying of solid ingesta, small bowel transit and its arrival in the caecum, a combined test was developed and applied in study 7, incorporating both 13C-OA and 13C-LU. Mathematical modelling of 13C recovery after ingestion of the dual test meal allowed calculation of small bowel half transit time, in addition to gastric and caecal parameters. Finally, minimised test protocols were developed for the 13C-OABT and 13C-LUBT in order to increase their clinical utility. The effects of decreasing the duration or frequency of breath collection on generation of intestinal transit parameters were assessed and linear regression models produced for each test based on the collection of 5 breath samples. Gastric t1/2, tlag and OCTT estimates from the reduced model and the full sampling protocols were highly correlated. However, in each case the reduced models were likely to underestimate these parameters when significantly prolonged, decreasing their sensitivity for the detection of delayed intestinal transit. The stable isotope breath tests offer a novel means of investigating features of intestinal motility and physiology in the horse and have potential value as both diagnostic modalities and humane research tools in this species. As the tests are non-invasive, simple to perform and do not require extensive equipment, they may be performed on site and the samples then submitted for isotopic analysis. Unlike other techniques for assessment of equine gastrointestinal motility, the stable isotope breath tests also provide an indirect measure of the transit rate of ingesta itself, which is directly relevant to the clinical situation. (Abstract shortened by ProQuest.)

Dynamical parton distributions of the nucleon and very small-x physics

Utilizing recent DIS measurements (F_{2,L}) and data on dilepton and high-E_{T} jet production we determine the dynamical parton distributions of the nucleon generated radiatively from valence-like positive input distributions at optimally chosen low resolution scales. These are compared with `standard' distributions generated from positive input distributions at some fixed and higher resolution scale. It is shown that up to the next to leading order NLO(\bar{MS}, DIS) of perturbative QCD considered in this paper, the uncertainties of the dynamical distributions are, as expected, smaller than those of their standard counterparts. This holds true in particular in the presently unexplored extremely small-x region relevant for evaluating ultrahigh energy cross sections in astrophysical applications. It is noted that our new dynamical distributions are compatible, within the presently determined uncertainties, with previously determined dynamical parton distributions.Comment: 21 pages, 2 tables, 16 figures, v2: added Ref.[60], replaced Fig.

Safety and efficacy of three trypanocides in confirmed field cases of trypanosomiasis in working equines in The Gambia: a prospective, randomised, non-inferiority trial

Background: Globally, working equines have a continued and growing socioeconomic role in supporting the livelihoods of between 300–600 million people in low income countries which is rarely recognised at a national or international level. Infectious diseases have significant impact on welfare and productivity in this population and equine trypanosomiasis is a priority disease due to its severity and prevalence. Strategies are required to improve the prevention, diagnosis, management and treatment of trypanosomiasis in equines and more data are required on the efficacy and safety of current trypanocidal drugs. Methods: A prospective randomised, open-label non-inferiority trial was performed in The Gambia on horses and donkeys that fulfilled 2/5 clinical inclusion criteria (anaemia, poor body condition, pyrexia, history of abortion, oedema). Following randomised trypanocidal treatment (diminazene diaceturate, melarsomine dihydrochloride or isometamidium chloride), animals were observed for immediate adverse drug reactions and follow-up assessment was performed at 1 and 2 weeks. Blood samples underwent PCR analysis with specific Trypanosoma sp. primers. Treatment efficacy was assessed by measuring changes in clinical parameters, clinicopathological results and PCR-status post-treatment after evaluating for bias. Using PCR status as the outcome variable, non-inferiority of isometamidium treatment was determined if the upper bound limit of a 2-sided 95% CI was less than 10%. Results: There was a significant beneficial effect upon the Trypanosoma sp. PCR positive population following trypanocidal treatment for all groups. The findings of clinical evaluation and PCR status supported a superior treatment effect for isometamidium. Melarsomine dihydrochloride efficacy was inferior to isometamidium. There were immediate, self-limiting side effects to isometamidium in donkeys (26%). Diminazene had the longest duration of action as judged by PCR status. Conclusions: The data support the continued use of isometamidium following careful dose titration in donkeys and diminazene for trypanosomiasis in equines using the doses and routes of administration reported

Variation in disease phenotype is marked in equine trypanosomiasis

Background: Equine trypanosomiasis is a severe and prevalent disease that has the greatest impact globally upon working equids due to its distribution across lower income countries. Morbidity and mortality rates are high; disease management strategies in endemic regions are ineffective and cost prohibitive. Individual variation in disease phenotype in other species suggests host factors could reveal novel treatment and control targets but has not been investigated in equids. Methods: A prospective clinical evaluation of equines presenting for a free veterinary examination was performed in hyperendemic villages in The Gambia. Age, body condition score and body weight were estimated by validated methods, and haematocrit and total protein concentration measured. Animals fulfilling 2 out of 5 clinical inclusion criteria (anaemia, poor body condition, pyrexia, history of abortion, oedema) for a diagnosis of trypanosomiasis received trypanocidal treatment with follow-up at 1 and 2 weeks. Blood samples underwent PCR analysis with specific Trypanosoma spp. primers and results were compared to the subject’s clinical and clinicopathological features. A mixed effects generalised linear model was generated to evaluate the association of infection status with degree of pyrexia and anaemia. Results: Morbidity was high within examined (n = 641) and selected (n = 247) study populations. PCR status was not associated with a defined disease phenotype; there was intra- and inter-species variability. Donkeys were more frequently Trypanosoma spp.-positive (P < 0.001) and febrile (P < 0.001) than horses, but infected horses were more anaemic (P < 0.001), and in poorer body condition (P < 0.001) than donkeys. Sex was correlated to disease phenotype: males were more anaemic (P = 0.03) and febrile (P < 0.001). Haemoparasite co-infections were more common than a single infection. Conclusions: There was evidence of diversity in trypanosomiasis clinical signs plus variable disease phenotypes within equid subpopulations that warrant further investigation. The complex co-infection profile of field cases requires greater consideration to optimise disease management

Retrospective study: laser excision versus combined laser, cryosurgery and intralesional 5-fluorouracil in the treatment of equine sarcoids

Background Laser excision is used routinely in the treatment of sarcoids but may be ineffective in cases where complete excision cannot be achieved. A multimodal approach is warranted in these cases. 5-FU may improve the lethal effect of cryosurgery as an adjunct to laser excision. Objectives To compare two treatment protocols for equine sarcoids, laser excision alone versus a combination protocol of laser excision, cryosurgery and 5-FU chemotherapy. Factors associated with sarcoid recurrence are also investigated. Study design Retrospective case controlled study. Results Eighty-four horses with 168 histologically confirmed sarcoids were included, with a median follow-up time of 39 months (IQR 21–62 months). Sarcoid recurrence at the treated site was reported in 38% of cases and in 23% of any individual sarcoid. No significant difference was demonstrated between treatment categories in either rate of sarcoid recurrence (p = 0.45 for any treated horse, p = 0.63 for individual sarcoid) or time to sarcoid recurrence (p = 0.73). Sarcoid recurrence was higher in horses with a greater number of sarcoids (OR 1.2 (1.0–1.5), p = 0.03); when treatment had been received prior to admission (OR 7.6 (2.0–33), p = 0.004). Horses with urogenital sarcoids or >1 mixed sarcoid experienced more rapid recurrence (HR 3.6 (1.3–10), p = 0.02 and HR 9.9 (3.3–30), p < 0.001) and recurrence was less rapid following the treatment of a horse's first sarcoid (HR 0.3 (0.1–0.7), p = 0.009). Main limitations Significant differences in case populations in each treatment category. Treatment selection was neither blinded nor randomised and missing data and recall bias limit the study's power. Sarcoid recurrence was owner reported. Conclusions When assessing the likelihood of sarcoid recurrence, characteristics of both the individual patient and sarcoid phenotype must be considered carefully when selecting a specific treatment protocol

Observation of Scaling Violations in Scaled Momentum Distributions at HERA

Charged particle production has been measured in deep inelastic scattering (DIS) events over a large range of $x$ and $Q^2$ using the ZEUS detector. The evolution of the scaled momentum, $x_p$, with $Q^2,$ in the range 10 to 1280 $GeV^2$, has been investigated in the current fragmentation region of the Breit frame. The results show clear evidence, in a single experiment, for scaling violations in scaled momenta as a function of $Q^2$.Comment: 21 pages including 4 figures, to be published in Physics Letters B. Two references adde

D* Production in Deep Inelastic Scattering at HERA

This paper presents measurements of D^{*\pm} production in deep inelastic scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The data have been taken with the ZEUS detector at HERA. The decay channel $D^{*+}\to (D^0 \to K^- \pi^+) \pi^+$ (+ c.c.) has been used in the study. The $e^+p$ cross section for inclusive D^{*\pm} production with $5<Q^2<100 GeV^2$ and $y<0.7$ is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region {$1.3<p_T(D^{*\pm})<9.0$ GeV and $| \eta(D^{*\pm}) |<1.5$}. Differential cross sections as functions of p_T(D^{*\pm}), $\eta(D^{*\pm}), W$ and $Q^2$ are compared with next-to-leading order QCD calculations based on the photon-gluon fusion production mechanism. After an extrapolation of the cross section to the full kinematic region in p_T(D^{*\pm}) and $\eta$(D^{*\pm}), the charm contribution $F_2^{c\bar{c}}(x,Q^2)$ to the proton structure function is determined for Bjorken $x$ between 2 $\cdot$ 10$^{-4}$ and 5 $\cdot$ 10$^{-3}$.Comment: 17 pages including 4 figure

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Comparison of loop-mediated isothermal amplification (LAMP) and PCR for the diagnosis of infection with Trypanosoma brucei ssp. in equids in The Gambia

Introduction: Infection of equids with Trypanosoma brucei (T. brucei) ssp. is of socioeconomic importance across sub-Saharan Africa as the disease often progresses to cause fatal meningoencephalitis. Loop-mediated isothermal amplification (LAMP) has been developed as a cost-effective molecular diagnostic test and is potentially applicable for use in field-based laboratories. Part I: Threshold levels for T. brucei ssp. detection by LAMP were determined using whole equine blood specimens spiked with known concentrations of parasites. Results were compared to OIE antemortem gold standard of T. brucei-PCR (TBR-PCR). Results I: Threshold for detection of T. brucei ssp. on extracted DNA from whole blood was 1 parasite/ml blood for LAMP and TBR-PCR, and there was excellent agreement (14/15) between tests at high (1 x 103/ml) concentrations of parasites. Detection threshold was 100 parasites/ml using LAMP on whole blood (LWB). Threshold for LWB improved to 10 parasites/ml with detergent included. Performance was excellent for LAMP at high (1 x 103/ml) concentrations of parasites (15/15, 100%) but was variable at lower concentrations. Agreement between tests was weak to moderate, with the highest for TBR-PCR and LAMP on DNA extracted from whole blood (Cohen’s kappa 0.95, 95% CI 0.64–1.00). Part II: A prospective cross-sectional study of working equids meeting clinical criteria for trypanosomiasis was undertaken in The Gambia. LAMP was evaluated against subsequent TBR-PCR. Results II: Whole blood samples from 321 equids in The Gambia were processed under field conditions. There was weak agreement between LWB and TBR-PCR (Cohen’s kappa 0.34, 95% CI 0.19–0.49) but excellent agreement when testing CSF (100% agreement on 6 samples). Conclusions: Findings support that LAMP is comparable to PCR when used on CSF samples in the field, an important tool for clinical decision making. Results suggest repeatability is low in animals with low parasitaemia. Negative samples should be interpreted in the context of clinical presentation