Magnetic resonance imaging findings in dogs with steroid-responsive meningitis-arteritis in the UK and their clinical significance: 53 cases (2013-2021).

OBJECTIVES: To describe the MRI findings in a UK referral population of dogs with steroid-responsive meningitis-arteritis and to determine if they were associated with any specific clinical features or outcomes. MATERIALS AND METHODS: We performed a multi-centre retrospective case series of dogs diagnosed with steroid-responsive meningitis-arteritis in the UK that underwent MRI. Blinded consensus review of the MRI studies was performed and the findings described. The presence or absence of specific MRI abnormalities were analysed for significant associations with presenting signs, results of investigations or case outcomes. RESULTS: Fifty-three dogs were included. The most common MRI findings were paravertebral muscle changes (30/53; 56.6%), meningeal contrast enhancement (13/41; 31.7%) and spinal cord parenchymal T2-W hyperintensity (15/53; 28.3%). Haemorrhage was observed in five of 53 (9.4%) cases - three intradural-extramedullary, one intramedullary and one extradural. Following binary logistic regressions, T2-W spinal cord parenchymal hyperintensity had a significant positive association with paresis/paralysis (odds ratio 14.86, 95% confidence interval 1.42 to 154.99) as did haemorrhage (odds ratio 16.12, confidence interval 2.05 to 126.73). Fifty-two (98.1%) dogs survived to discharge. Relapse occurred in nine of 29 (31.0%) dogs with sufficient follow-up, and no MRI finding had a significant relationship with its occurrence. CLINICAL SIGNIFICANCE: Magnetic resonance imaging findings for steroid-responsive meningitis-arteritis can be severe and extensive, as can the clinical presentation. The presence of paresis/paralysis should raise concern for haemorrhage, though most dogs still have a good prognosis.

Dealing with double trouble: Combination deworming against double-drug resistant cyathostomins.

An alternative control regimen for drug-resistant parasites is combination deworming, where two drugs with different modes of action are administered simultaneously to target the same parasite. Few studies have investigated this in equine cyathostomins. We previously reported that an oxibendazole (OBZ) and pyrantel pamoate (PYR) combination was not sustainable against a cyathostomin population with high levels of OBZ and PYR resistance. This study consisted of a field study and two computer simulations to evaluate the efficacy of a moxidectin-oxibendazole (MOX-OBZ) combination against the same cyathostomin population. In the field study, anthelmintic treatments occurred when ten horses exceeded 100 eggs per gram. Fecal egg counts and efficacy evaluations were performed every two weeks. The two simulations utilized weather data as well as equine and parasite population parameters from the field study. The first simulation repeated the treatment schedule used in the field study over a 40 year period. The second evaluated efficacies of combination treatments using selective therapy over 40 years. In the field study, efficacies of MOX and both combination treatments were 100%. The egg reappearance period for MOX was 16 weeks, and the two combination treatments were 12 and 18 weeks. The first (46.7%) and last (40.1%) OBZ efficacies were not significantly different from each other. In the simulation study, the combination treatment delayed MOX resistance development compared to when MOX was used as a single active. This occurred despite the low efficacy of OBZ. The second set of simulations identified combination treatments used with selective therapy to be the most effective at delaying MOX resistance. Overall, this study supports the use of combination treatment against drug-resistant cyathostomins, when one of the actives exhibits high efficacy, and demonstrates benefits of this approach despite substantially lowered efficacy of the other active ingredient.

Origin of Perpendicular Magnetic Anisotropy and Large Orbital Moment in Fe Atoms on MgO.

We report on the magnetic properties of individual Fe atoms deposited on MgO(100) thin films probed by x-ray magnetic circular dichroism and scanning tunneling spectroscopy. We show that the Fe atoms have strong perpendicular magnetic anisotropy with a zero-field splitting of 14.0±0.3 meV/atom. This is a factor of 10 larger than the interface anisotropy of epitaxial Fe layers on MgO and the largest value reported for Fe atoms adsorbed on surfaces. The interplay between the ligand field at the O adsorption sites and spin-orbit coupling is analyzed by density functional theory and multiplet calculations, providing a comprehensive model of the magnetic properties of Fe atoms in a low-symmetry bonding environment.

Development and testing of a field diagnostic assay for peste des petits ruminants virus.

We have developed an immunochromatographic test for the diagnosis of peste des petits ruminants (PPR) under field conditions. The diagnostic assay has been tested in the laboratory and also under field conditions in Ivory Coast, Pakistan, Ethiopia and Uganda. The test is carried out on a superficial swab sample (ocular or nasal) and showed a sensitivity of 84% relative to PCR. The specificity was 95% over all nasal and ocular samples. The test detected as little as 10(3) TCID50 (50% tissue culture infectious doses) of cell culture-grown virus, and detected virus isolates representing all four known genetic lineages of peste des petits ruminants virus. Virus could be detected in swabs from animals as early as 4 days post-infection, at a time when clinical signs were minimal. Feedback from field trials was uniformly positive, suggesting that this diagnostic tool may be useful for current efforts to control the spread of PPR.

Modelling the expected rate of laboratory biosafety breakdowns involving rinderpest virus in the post-eradication era.

Now that we are in the rinderpest post-eradication era, attention is focused on the risk of re-introduction. A semi-quantitative risk assessment identified accidental use of rinderpest virus in laboratories as the most likely cause of re-introduction. However there is little data available on the rates of laboratory biosafety breakdowns in general. In addition, any predictions based on past events are subject to various uncertainties. The aims of this study were therefore to investigate the potential usefulness of historical data for predicting the future risk of rinderpest release via laboratory biosafety breakdowns, and to investigate the impacts of the various uncertainties on these predictions. Data were collected using a worldwide online survey of laboratories, a structured search of ProMED reports and discussion with experts. A stochastic model was constructed to predict the number of laboratory biosafety breakdowns involving rinderpest that will occur over the next 10 years, based on: (1) the historical rate of biosafety breakdowns; and (2) the change in the number of laboratories that will have rinderpest virus in the next 10 years compared to historically. The search identified five breakdowns, all of which occurred during 1970-2000 and all of which were identified via discussions with experts. Assuming that our search for historical events had a sensitivity of over 60% and there has been at least a 40% reduction in the underlying risk (attributable to decreased laboratory activity post eradication) the most likely number of biosafety events worldwide was estimated to be zero over a 10 year period. However, the risk of at least one biosafety breakdown remains greater than 1 in 10,000 unless the sensitivity was at least 99% or the number of laboratories has decreased by at least 99% (based on 2000-2010 during which there were no biosafety breakdowns).

Androgens increase survival of adult-born neurons in the dentate gyrus by an androgen receptor-dependent mechanism in male rats.

Gonadal steroids are potent regulators of adult neurogenesis. We previously reported that androgens, such as testosterone (T) and dihydrotestosterone (DHT), but not estradiol, increased the survival of new neurons in the dentate gyrus of the male rat. These results suggest androgens regulate hippocampal neurogenesis via the androgen receptor (AR). To test this supposition, we examined the role of ARs in hippocampal neurogenesis using 2 different approaches. In experiment 1, we examined neurogenesis in male rats insensitive to androgens due to a naturally occurring mutation in the gene encoding the AR (termed testicular feminization mutation) compared with wild-type males. In experiment 2, we injected the AR antagonist, flutamide, into castrated male rats and compared neurogenesis levels in the dentate gyrus of DHT and oil-treated controls. In experiment 1, chronic T increased hippocampal neurogenesis in wild-type males but not in androgen-insensitive testicular feminization mutation males. In experiment 2, DHT increased hippocampal neurogenesis via cell survival, an effect that was blocked by concurrent treatment with flutamide. DHT, however, did not affect cell proliferation. Interestingly, cells expressing doublecortin, a marker of immature neurons, did not colabel with ARs in the dentate gyrus, but ARs were robustly expressed in other regions of the hippocampus. Together these studies provide complementary evidence that androgens regulate adult neurogenesis in the hippocampus via the AR but at a site other than the dentate gyrus. Understanding where in the brain androgens act to increase the survival of new neurons in the adult brain may have implications for neurodegenerative disorders.

Rapid isolation of leukocyte subsets from fresh and cryopreserved peripheral blood mononuclear cells in clinical research.

Isolation and processing blood into leukocyte subsets are important processes in research. Although methods have been developed to fractionate small volumes of blood, optimizing the methods and balancing the underlying costs are often necessary. The need for such optimization is particularly critical when processing larger volumes of blood. We describe a simple and reproducible method for processing larger volumes of fresh blood rapidly and consistently, which yields peripheral blood mononuclear cells (PBMCs) and leukocyte subsets with high purity (81-96%; n=13) and higher yields relative to stored blood. RNA isolated from these cells was found to be suitable for downstream applications. Blood stored for 24 hours (n=4) before processing resulted in significantly lower yields of PBMCs (58 percent lower), T cells (52 percent lower), B cells (21 percent lower) and monocytes (25 percent lower) compared to fresh blood. However, the purity of the fractionated cells was comparable to that obtained with fresh blood. Furthermore, we report that the yield and purity of the leukocyte subsets isolated from cryopreserved PBMCs (n=4) were not compromised.

Integration of participatory approaches into surveillance systems.

Animal health surveillance is essential for protecting public health, enhancing access to international markets for animals and their products, and improving animal health, production and welfare. It is of vital importance for protecting and improving the livelihoods of diverse groups of livestock keepers and stakeholders in livestock value chains. Surveillance systems consist of sets of complementary components which generate information to inform risk assessment, decision-making and policy formulation for both national programmes and international trade. Participatory approaches have the potential to add value to surveillance systems by enhancing their performance, especially their sensitivity and timeliness, and encouraging the inclusion of marginalised groups. This paper summarises key considerations in the assessment and design of animal health surveillance and discusses how participatory approaches can be integrated into comprehensive surveillance systems, leading to a more effective overall outcome for both domestic and international purposes.

Analysis of the antiferromagnetic phase transitions of the 2D Kondo lattice.

We study the antiferromagnetic quantum phase transition of a 2D Kondo-Heisenberg square lattice using the nonlinear sigma model. A renormalization group analysis of the competing Kondo-RKKY interaction is carried out to one-loop order in the expansion, and a new quantum critical point (QCP) strongly affected by Kondo fluctuations is found. Near this QCP, the spin-wave velocity scales logarithmically, i.e., breakdown of hydrodynamic behavior, and the spin wave is logarithmically frozen out. The renormalization group results also allow us to propose a new phase diagram near the antiferromagnetic fixed point of this 2D Kondo lattice model.

Planar spin-transfer device with a dynamic polarizer.

In planar nano-magnetic devices magnetization direction is kept close to a given plane by the large easy-plane magnetic anisotropy, for example by the shape anisotropy in a thin film. In this case magnetization shows effectively in-plane dynamics with only one angle required for its description. Moreover, the motion can become overdamped even for small values of Gilbert damping. We derive the equations of effective in-plane dynamics in the presence of spin-transfer torques. The simplifications achieved in the overdamped regime allow to study systems with several dynamic magnetic pieces ("free layers"). A transition from a spin-transfer device with a static polarizer to a device with two equivalent magnets is observed. When the size difference between the magnets is less than critical, the device does not exhibit switching, but goes directly into the "windmill" precession state.

First-principles calculation of the single impurity surface Kondo resonance.

We perform first-principles calculations of the surface and bulk wave functions of the Cu(111) surface and their hybridization energies to a Co adatom, including the potential scattering from the Co. By analyzing the calculated hybridization energies, we find the bulk states dominate the contribution to the Kondo temperature, in agreement with recent experiments. Furthermore, we also calculate the tunneling conductance of a scanning tunneling microscope and compare our results with recent experiments of Co impurities in the Cu(111) surface. Good quantitative agreement is found at short parallel impurity-tip distances (<6 A). Our results indicate the need for a new formulation of the problem at larger distances.

A prospective randomised controlled trial of the Kiwi Omnicup versus conventional ventouse cups for vacuum-assisted vaginal delivery.

OBJECTIVE: To evaluate the performance and safety of the Kiwi Omnicup and compare it to conventional vacuum cups in routine clinical practice. DESIGN: A randomised controlled trial of the Kiwi Omnicup versus conventional vacuum cups. SETTING: Queen Charlotte's and Chelsea Hospital, a tertiary referral hospital in London from April 2001 to March 2004. POPULATION: Women requiring assisted vaginal delivery by ventouse. METHODS: Women were randomised to the Kiwi Omnicup (n=206) or conventional vacuum cups (n=198). Data regarding maternal demographics, labour, mode of delivery and maternal and neonatal outcome were collected. MAIN OUTCOME MEASURES: Failure of delivery with instrument of first choice. RESULTS: The Kiwi Omnicup was less successful at delivery with instrument of first choice than the conventional ventouse, failure rate 30.1 versus 19.2% (RR 1.58; 95% CI 1.10-2.24). It was associated with a greater number of cup detachments (mean 0.68 compared with 0.28, with 44% compared with 18% having at least one detachment [P<0.0001]). There was no difference in the incidence of severe maternal trauma, and there were no cases of serious neonatal injury. CONCLUSIONS: The Kiwi Omnicup is less successful than conventional ventouse in achieving vaginal delivery, but its safety profile is comparable.

Distribution of androgen receptor immunoreactivity in the brainstem of male rats.

Gonadal steroids such as testosterone and estrogen are necessary for the normal activation of male rat sexual behavior. The medial preoptic area (MPOA), an important neural substrate regulating mating, accumulates steroids and also expresses functional androgen receptors (AR). The MPOA is intimately connected with other regions implicated in copulation, such as the bed nucleus of the stria terminalis and medial amygdala. Inputs to the MPOA arise from several areas within the brainstem, synapsing preferentially onto steroid sensitive MPOA cells which are activated during sexual activity. Given that little is known about the distribution of AR protein in the brainstem of male rats, we mapped the distribution of AR expressing cells in the pons and medulla using immunocytochemistry. In agreement with previous reports, AR immunoreactivity (AR-ir) was detected in ventral spinal motoneurons and interneurons. In addition, AR-ir was detected in areas corresponding to the solitary tract, lateral paragigantocellular and alpha and ventral divisions of the gigantocellular reticular nuclei, area postrema, raphe pallidus, ambiguus nucleus, and intermediate reticular nucleus. Several regions within the pons contained AR-ir, such as the tegmental and central gray, parabrachial nucleus, locus coeruleus, Barrington's nucleus, periaqueductal gray, and dorsal raphe. In contrast with in situ hybridization studies, auditory and somatosensory areas were AR-ir negative, and, except for very light staining in the prepositus nucleus, areas carrying vestibular information did not display AR-ir. Additionally, cranial nerve motoneurons of the hypoglossal, facial, dorsal vagus, and spinal trigeminal did not display AR-ir in contrast to previous reports. The data presented here indicate that androgens may influence numerous cell groups within the brainstem. Some of these probably constitute a steroid sensitive circuit linking the MPOA to motoneurons in the spinal cord via androgen responsive cells in the caudal ventral medulla.

Social representations of stem cell research and preimplantation genetic diagnosis.

The study examined public thinking about stem cell research and preimplantation genetic diagnosis (PGD) using social representation theory. Social representation theory is concerned with the movement of scientific knowledge from the realm of the specialist into lay knowledge. Participants were interviewed and the data analysed qualitatively. Three social representations were found for both stem cell research and PGD. For stem cell research, one was based on irrational fears, one was based on social concerns for the technology and the final was based on the notion of the 'slippery slope'. For PGD, the first social representation was based on concern for the human impact, the second was based, again, on irrational fear, and the third was based on medical applications. Participants rated stem cell research more positively than PGD. It was concluded that while information about both topics is in the process of being transformed, knowledge of stem cell research has been transformed into lay knowledge more completely than knowledge of PGD. Directions for future research included attitude surveys and discourse analyses.

Participatory analysis of seasonal incidences of diseases of cattle, disease vectors and rainfall in southern Sudan.

During an investigation into a chronic wasting disease in southern Sudanese cattle, a participatory appraisal method called a 'seasonal calendar' was used to understand local perceptions of seasonal variations in cattle diseases, disease vectors, intermediate hosts and rainfall. Repetition of a standardized seasonal calendar with Dinka informants demonstrated good reproducibility of the method. Comparison of rainfall data produced by seasonal calendars and objective measures of rainfall demonstrated good validity of the seasonal calendar method. Subjective assessment of seasonal calendar scoring patterns by veterinarians indicated that herders' perceptions of seasonal populations of biting flies, ticks and snails were similar to modern veterinary knowledge. The uses of seasonal calendars in veterinary epidemiology are discussed.

Usefulness of concurrent Papanicolaou smear at time of cervical biopsy.

The reliability and cost-effectiveness of a repeat Papanicolaou (Pap) smear performed at the time of colposcopic biopsy is uncertain. To evaluate the usefulness of this practice, Pap smear and biopsy results of 718 patients were reviewed and compared: 619 patients had Pap smears performed prior to colposcopy with a 1.1% false-negative rate, 97.5% sensitivity, and 83.6% positive predictive value. Ninety-nine patients had Pap smears performed at the time of colposcopy with a 19.1% false-negative rate, 56.8% sensitivity, and 92.6% positive predictive value. Repeat Pap smear at the time of colposcopy resulted in significant changes in the management of only 2 patients (2%) and more careful follow-up in one (1%). Pap smears performed at colposcopic biopsy are less sensitive than those done prior to biopsy (P < 0.001). The clinical benefit of this practice is marginal, considering the added costs and potential detrimental effects to the colposcopic examination, provided patients receive adequate follow-up.

Nongynecologic cytology turnaround time: a College of American Pathologists Q-Probes study of 180 laboratories.

OBJECTIVES: To determine the turnaround time for nongynecologic cytology and to identify laboratory and specimen characteristics associated with variations in turnaround time. DESIGN AND SETTING: Prospective evaluation of nongynecologic cytology turnaround times in 180 laboratories. MAIN OUTCOME MEASURE: Nongynecologic cytology case turnaround time. RESULTS: Participants from 180 laboratories submitted turnaround times for 16 950 nongynecologic cytology cases and submitted information describing their laboratories' practice characteristics relating to the processing of nongynecologic cytology specimens. Half of the participating laboratories had mean receipt to report turnaround times of 1.6 calendar days or less and were able to complete 90% of their cases within 3.0 calendar days. Ten percent of participants had mean turnaround times greater than 3.2 days and required 6.0 or more days to report 90% of their cases. Longer turnaround times were associated with processing fluid and fine-needle aspiration specimens, issuing atypical/suspicious for malignancy and nondiagnostic diagnoses, having cytotechnologist students screen slides, having to contact the physician offices for additional information, having to retrieve prior case material for review, and having to perform cell blocks and/or special stains. CONCLUSION: There is an opportunity for laboratories to shorten nongynecologic turnaround time by altering certain laboratory practices.

Participatory diagnosis of a chronic wasting disease in cattle in southern Sudan.

In southern Sudan, livestock keepers identified a chronic wasting disease in adult cattle as one of their most-serious animal-health problems. Participatory-appraisal (PA) methods and conventional veterinary-investigation methods were used to characterise the chronic wasting disease and identify linkages between indigenous knowledge and modern veterinary knowledge. The local characterisation of chronic wasting encompassed trypanosomosis, fasciolosis, parasitic gastroenteritis and schistosomosis (as both single and mixed infections).A standardised PA method called matrix scoring had good reproducibility when investigating local perceptions of disease-signs and disease causes. Comparison of matrix-scoring results showed much overlap with modern veterinary descriptions of cattle diseases and the results of conventional veterinary investigation. Applications of PA methods in remote areas with very limited veterinary infrastructure are discussed. The validation of data derived from PA is discussed by reference to the low sensitivity of 'field-friendly' diagnostic tests for important cattle diseases.

Race, anthropometric factors, and stage at diagnosis of breast cancer.

A recent study suggested that the greater prevalence of severe obesity among African-American women explained almost one third of the observed differences between African-American and White women in stage at diagnosis of breast cancer. The objective of this investigation was to attempt to replicate these findings in a second, larger population and to expand the analyses by including a measure of body fat distribution, the waist:hip ratio. The authors used data from a population-based study in North Carolina comprising 791 breast cancer cases (302 in African-American women and 489 in White women) diagnosed between 1993 and 1996. African-American women were more likely to have later-stage (TNM stage >/=II) breast cancer (odds ratio (OR) = 2.2; 95% confidence interval (CI): 1.6, 2.9). They also were much more likely to be severely obese (body mass index >/=32.3) (OR = 9.7; 95% CI: 6.5, 14.5) and to be in the highest tertile of waist:hip ratio (OR = 5.7; 95% CI: 3.8, 8.6). In multivariate logistic regression models, adjustment for waist:hip ratio reduced the odds ratio for later-stage disease in African-American women by 20%; adjustment for both waist:hip ratio and severe obesity reduced the odds ratio by 27%. These observations suggest that obesity and body fat distribution, in addition to socioeconomic and medical care factors, contribute to racial differences in stage at breast cancer diagnosis.

Is variation in quality of mammographic services race linked?

The purpose of this investigation was to (1) determine whether there was variability in the quality of services offered in mammography facilities across Connecticut and (2) determine whether African American women were more likely than white women to receive mammograms in facilities that offered substandard services. Since most facilities do not routinely record information on race, this investigation represents a unique opportunity to address the question of race-linked variation in the quality of screening mammography. Information on equipment, personnel, and record keeping in mammography facilities was used to construct indices that represented separate domains of quality: technical attributes, educational practices, and tracking of clients. While some variation in the quality of mammography services was found, there were no significant differences between the two race categories in the mean scores for each of three quality indices. Thus, variation in quality of screening mammographic services does not appear to be race linked.