On the biological and genetic diversity in Neospora caninum

Published: 22 March 2010Neospora caninum is a parasite regarded a major cause of foetal loss in cattle. A key requirement to an understanding of the epidemiology and pathogenicity of N. caninum is knowledge of the biological characteristics of the species and the genetic diversity within it. Due to the broad intermediate host range of the species, worldwide geographical distribution and its capacity for sexual reproduction, significant biological and genetic differences might be expected to exist. N. caninum has now been isolated from a variety of different host species including dogs and cattle. Although isolates of this parasite show only minor differences in ultrastructure, considerable differences have been reported in pathogenicity using mainly mouse models. At the DNA level, marked levels of polymorphism between isolates were detected in mini- and microsatellites found in the genome of N. caninum. Knowledge of what drives the biological differences that have been observed between the various isolates at the molecular level is crucial in aiding our understanding of the epidemiology of this parasite and, in turn, the development of efficacious strategies, such as live vaccines, for controlling its impact. The purpose of this review is to document and discuss for the first time, the nature of the diversity found within the species Neospora caninum.Sarwat E. Al-Qassab, Michael P. Reichel and John T. Elli

Anderson impurity in pseudo-gap Fermi systems

We use the numerical renormalization group method to study an Anderson impurity in a conduction band with the density of states varying as rho(omega) \propto |omega|^r with r>0. We find two different fixed points: a local-moment fixed point with the impurity effectively decoupled from the band and a strong-coupling fixed point with a partially screened impurity spin. The specific heat and the spin-susceptibility show powerlaw behaviour with different exponents in strong-coupling and local-moment regime. We also calculate the impurity spectral function which diverges (vanishes) with |omega|^{-r} (|\omega|^r) in the strong-coupling (local moment) regime.Comment: 8 pages, LaTeX, 4 figures includes as eps-file

Economic evaluation of ASCOT-BPLA: Antihypertensive treatment with an amlodipine-based regimen is cost-effective compared to an atenolol-based regimen

Copyright © 2010 BMJ Publishing Group Ltd & British Cardiovascular Society. Internal or personal use of this material is permitted. However, permission to reprint/republish this material must be obtained from the Publisher.Objective: To compare the cost effectiveness of an amlodipine-based strategy and an atenolol-based strategy in the treatment of hypertension in the UK and Sweden. Design: A prospective, randomised trial complemented with a Markov model to assess long-term costs and health effects. Setting: Primary care. Patients: Patients with moderate hypertension and three or more additional risk factors. Interventions: Amlodipine 5–10 mg with perindopril 4–8 mg added as needed or atenolol 50–100 mg with bendroflumethiazide 1.25–2.5 mg and potassium added as needed Main outcome measures: Cost per cardiovascular event and procedure avoided, and cost per quality-adjusted life-year gained. Results: In the UK, the cost to avoid one cardiovascular event or procedure would be €18 965, and the cost to gain one quality-adjusted life-year would be €21 875. The corresponding figures for Sweden were €13 210 and €16 856. Conclusions: Compared with the thresholds applied by NICE and in the Swedish National Board of Health and Welfare’s Guidelines for Cardiac Care, an amlodipine-based regimen is cost effective for the treatment of hypertension compared with an atenolol-based regimen in the population studied.The study was supported by the principal funding source, Pfizer, New York, USA

DNA repair deficiency biomarkers and the 70-gene ultra-high risk signature as predictors of veliparib/carboplatin response in the I-SPY 2 breast cancer trial.

Veliparib combined with carboplatin (VC) was an experimental regimen evaluated in the biomarker-rich neoadjuvant I-SPY 2 trial for breast cancer. VC showed improved efficacy in the triple negative signature. However, not all triple negative patients achieved pathologic complete response and some HR+HER2- patients responded. Pre-specified analysis of five DNA repair deficiency biomarkers (BRCA1/2 germline mutation; PARPi-7, BRCA1ness, and CIN70 expression signatures; and PARP1 protein) was performed on 116 HER2- patients (VC: 72 and concurrent controls: 44). We also evaluated the 70-gene ultra-high risk signature (MP1/2), one of the biomarkers used to define subtype in the trial. We used logistic modeling to assess biomarker performance. Successful biomarkers were combined using a simple voting scheme to refine the 'predicted sensitive' group and Bayesian modeling used to estimate the pathologic complete response rates. BRCA1/2 germline mutation status associated with VC response, but its low prevalence precluded further evaluation. PARPi-7, BRCA1ness, and MP1/2 specifically associated with response in the VC arm but not the control arm. Neither CIN70 nor PARP1 protein specifically predicted VC response. When we combined the PARPi-7 and MP1/2 classifications, the 42% of triple negative patients who were PARPi7-high and MP2 had an estimated pCR rate of 75% in the VC arm. Only 11% of HR+/HER2- patients were PARPi7-high and MP2; but these patients were also more responsive to VC with estimated pathologic complete response rates of 41%. PARPi-7, BRCA1ness and MP1/2 signatures may help refine predictions of VC response, thereby improving patient care

Broad-band X-ray spectral evolution of GX 339-4 during a state transition

We report on X-ray and soft gamma-ray observations of the black-hole candidate GX 339-4 during its 2007 outburst, performed with the RXTE and INTEGRAL satellites. The hardness-intensity diagram of all RXTE/PCA data combined shows a q-shaped track similar to that observed in previous outbursts.The evolution in the diagram suggested that a transition from hard-intermediate state to soft-intermediate state occurred, simultaneously with INTEGRAL observations performed in March. The transition is confirmed by the timing analysis presented in this work, which reveals that a weak type-A quasi-periodic oscillation (QPO) replaces a strong type-C QPO. At the same time, spectral analysis shows that the flux of the high-energy component shows a significant decrease in its flux. However, we observe a delay (roughly one day) between variations of the spectral parameters of the high-energy component and changes in the flux and timing properties. The changes in the high-energy component can be explained either in terms the high-energy cut-off or in terms of a variations in the reflection component. We compare our results with those from a similar transition during the 2004 outburst of GX 339-4.Comment: 8 pages, 6 figures, accepted for publication in MNRAS Main Journa

Lessons from the evaluation of the UK's NHS R&D Implementation Methods Programme

Background: Concern about the effective use of research was a major factor behind the creation of the NHS R&D Programme in 1991. In 1994, an advisory group was established to identify research priorities in research implementation. The Implementation Methods Programme (IMP) flowed from this, and its commissioning group funded 36 projects. In 2000 responsibility for the programme passed to the National Co-ordinating Centre for NHS Service Delivery and Organisation R&D, which asked the Health Economics Research Group (HERG), Brunel University, to conduct an evaluation in 2002. By then most projects had been completed. This evaluation was intended to cover: the quality of outputs, lessons to be learnt about the communication strategy and the commissioning process, and the benefits from the projects. Methods: We adopted a wide range of quantitative and qualitative methods. They included: documentary analysis, interviews with key actors, questionnaires to the funded lead researchers, questionnaires to potential users, and desk analysis. Results: Quantitative assessment of outputs and dissemination revealed that the IMP funded useful research projects, some of which had considerable impact against the various categories in the HERG payback model, such as publications, further research, research training, impact on health policy, and clinical practice. Qualitative findings from interviews with advisory and commissioning group members indicated that when the IMP was established, implementation research was a relatively unexplored field. This was reflected in the understanding brought to their roles by members of the advisory and commissioning groups, in the way priorities for research were chosen and developed, and in how the research projects were commissioned. The ideological and methodological debates associated with these decisions have continued among those working in this field. The need for an effective communication strategy for the programme as a whole was particularly important. However, such a strategy was never developed, making it difficult to establish the general influence of the IMP as a programme. Conclusion: Our findings about the impact of the work funded, and the difficulties faced by those developing the IMP, have implications for the development of strategic programmes of research in general, as well as for the development of more effective research in this field

Tracing the jet contribution to the mid-IR over the 2005 outburst of GRO J1655-40 via broadband spectral modeling

We present new results from a multi-wavelength (radio/infrared/optical/X-ray) study of the black hole X-ray binary GRO J1655-40 during its 2005 outburst. We detected, for the first time, mid-infrared emission at 24 um from the compact jet of a black hole X-ray binary during its hard state, when the source shows emission from a radio compact jet as well as a strong non-thermal hard X-ray component. These detections strongly constrain the optically thick part of the synchrotron spectrum of the compact jet, which is consistent with being flat over four orders of magnitude in frequency. Moreover, using this unprecedented coverage, and especially thanks to the new Spitzer observations, we can test broadband disk and jet models during the hard state. Two of the hard state broadband spectra are reasonably well fitted using a jet model with parameters overall similar to those previously found for Cyg X-1 and GX 339-4. Differences are also present; most notably, the jet power in GRO J1655-40 appears to be a factor of at least ~3-5 higher (depending on the distance) than that of Cyg X-1 and GX 339-4 at comparable disk luminosities. Furthermore, a few discrepancies between the model and the data, previously not found for the other two black hole systems for which there was no mid-IR/IR and optical coverage, are evident, and will help to constrain and refine theoretical models.Comment: accepted for publication in Ap

Specific heat of Ce_{0.8}La_{0.2}Al_{3} in magnetic fields: a test of the anisotropic Kondo picture

The specific heat C of Ce_{0.8}La_{0.2}Al_{3} has been measured as a function of temperature T in magnetic fields up to 14 T. A large peak in C at 2.3 K has recently been ascribed to an anisotropic Kondo effect in this compound. A 14-T field depresses the temperature of the peak by only 0.2 K, but strongly reduces its height. The corresponding peak in C/T shifts from 2.1 K at zero field to 1.7 K at 14 T. The extrapolated specific heat coefficient C/T(T->0) increases with field over the range studied. We show that these trends are inconsistent with the anisotropic Kondo model.Comment: 4 pages, 5 figures, ReVTeX + eps

The demand for sports and exercise: Results from an illustrative survey

Funding from the Department of Health policy research programme was used in this study.There is a paucity of empirical evidence on the extent to which price and perceived benefits affect the level of participation in sports and exercise. Using an illustrative sample of 60 adults at Brunel University, West London, we investigate the determinants of demand for sports and exercise. The data were collected through face-to-face interviews that covered indicators of sports and exercise behaviour; money/time price and perceived benefits of participation; and socio- economic/demographic details. Count, linear and probit regression models were fitted as appropriate. Seventy eight per cent of the sample participated in sports and exercise and spent an average of £27 per month and an average of 20 min travelling per occasion of sports and exercise. The demand for sport and exercise was negatively associated with time (travel or access time) and ‘variable’ price and positively correlated with ‘fixed’ price. Demand was price inelastic, except in the case of meeting the UK government’s recommended level of participation, which is time price elastic (elasticity = −2.2). The implications of data from a larger nationally representative sample as well as the role of economic incentives in influencing uptake of sports and exercise are discussed.This article is available through the Brunel Open Access Publishing Fund

Multi-Wavelength Coverage of State Transitions in the New Black Hole X-Ray Binary Swift J1910.2-0546

Understanding how black holes accrete and supply feedback to their environment is one of the outstanding challenges of modern astrophysics. Swift J1910.2-0546 is a candidate black hole low-mass X-ray binary that was discovered in 2012 when it entered an accretion outburst. To investigate the binary configuration and the accretion morphology we monitored the evolution of the outburst for ~3 months at X-ray, UV, optical (B,V,R,I), and near-infrared (J,H,K) wavelengths using Swift and SMARTS. The source evolved from a hard to a soft X-ray spectral state with a relatively cold accretion disk that peaked at ~0.5 keV. A Chandra/HETG spectrum obtained during this soft state did not reveal signatures of an ionized disk wind. Both the low disk temperature and the absence of a detectable wind could indicate that the system is viewed at relatively low inclination. The multi-wavelength light curves revealed two notable features that appear to be related to X-ray state changes. Firstly, a prominent flux decrease was observed in all wavebands ~1-2 weeks before the source entered the soft state. This dip occurred in (0.6-10 keV) X-rays ~6 days later than at longer wavelengths, which could possibly reflect the viscous time scale of the disk. Secondly, about two weeks after the source transitioned back into the hard state, the UV emission significantly increased while the X-rays steadily decayed. We discuss how these observations may reflect changes in the accretion flow morphology, perhaps related to the quenching/launch of a jet or the collapse/recovery of a hot flow.Comment: 8 pages, 5 figures, 1 table. To be published in Ap