Interferon beta in multiple sclerosis: experience in a British specialist multiple sclerosis centre

Background: The efficacy of interferon beta (IFN beta) is well established in relapsing-remitting multiple sclerosis (MS). However, the use of this drug in clinical practice is complex, especially because it is only partially effective, its long term efficacy and side effects are unknown, its efficacy may be abrogated by the development of neutralising antibodies, compliance is variable, and its cost effectiveness is controversial. Objectives and Methods: Analysis of a prospectively followed up series of 101 MS patients treated with IFN beta was undertaken to: (1) monitor the outcome of IFN beta treatment in clinical practice; (2) compare the immunogenicity of the three commercial IFN beta preparations available; (3) assess the proportion of patients fulfilling the current guidelines of the Association of British Neurologists for stopping IFN beta therapy. Results: During a median treatment period of 26 months (range 2–85), the relapse rate decreased by 41%. Although the reduction in the relapse rate was similar for all three commercial products, none of the Avonex treated patients were relapse free, compared with 19% of the Betaferon treated and 27% of the Rebif treated patients (p=0.02). Neutralising antibodies were not detected in Avonex treated patients (0 of 18), compared with 12 of 32 (38%) Betaferon treated and 10 of 23 (44%) Rebif treated patients (p=0.02). Forty of 101 (40%) patients satisfied the current (2001) Association of British Neurologists criteria for stopping IFN beta treatment at some stage during their treatment. Conclusion: IFN beta is effective in reducing the relapse rate in patients with relapsing-remitting MS in routine clinical practice. However, after a median treatment duration of 26 months, 40% of initially relapsing-remitting MS patients seem to have ongoing disease activity, presenting as disabling relapses or insidious progression

A longitudinal study of abnormalities on MRI and disability from multiple sclerosis

Background: In patients with isolated syndromes that are clinically suggestive of multiple sclerosis, such as optic neuritis or brain-stem or spinal cord syndromes, the presence of lesions as determined by T2-weighted magnetic resonance imaging (MRI) of the brain increases the likelihood that multiple sclerosis will develop. We sought to determine the relation between early lesion volume, changes in volume, and long-term disability. Methods: Seventy-one patients in a serial MRI study of patients with isolated syndromes were reassessed after a mean of 14.1 years. Disability was measured with the use of Kurtzke's Expanded Disability Status Scale (EDSS; possible range, 0 to 10, with a higher score indicating a greater degree of disability). Results: Clinically definite multiple sclerosis developed in 44 of the 50 patients (88 percent) with abnormal results on MRI at presentation and in 4 of 21 patients (19 percent) with normal results on MRI. The median EDSS score at follow-up for those with multiple sclerosis was 3.25 (range, 0 to 10); 31 percent had an EDSS score of 6 or more (including three patients whose deaths were due to multiple sclerosis). The EDSS score at 14 years correlated moderately with lesion volume on MRI at 5 years (r=0.60) and with the increase in lesion volume over the first 5 years (r=0.61). Conclusions: In patients who first present with isolated syndromes suggestive of multiple sclerosis, the increases in the volume of the lesions seen on magnetic resonance imaging of the brain in the first five years correlate with the degree of long-term disability from multiple sclerosis. This relation is only moderate, so the volume of the lesions alone may not be an adequate basis for decisions about the use of disease-modifying treatment

Quantum Scattering from Classical Field Theory

We show that scattering amplitudes between initial wave packet states and certain coherent final states can be computed in a systematic weak coupling expansion about classical solutions satisfying initial value conditions. The initial value conditions are such as to make the solution of the classical field equations amenable to numerical methods. We propose a practical procedure for computing classical solutions which contribute to high energy two particle scattering amplitudes. We consider in this regard the implications of a recent numerical simulation in classical SU(2) Yang-Mills theory for multiparticle scattering in quantum gauge theories and speculate on its generalization to electroweak theory. The generalization of our results to complex trajectories allows its application to it any wave packet to coherent state transition. Finally, we discuss the relevance of these results to the issues of baryon number violation and multiparticle scattering at high energies.Comment: 20 pages, JHU-TIPAC-940003, HUTP-A0/007, Latex, uses prepictex.tex, pictex.tex, and postpictex.tex (available by ftp from [email protected]) to produce figure

Effect of gluon-exchange pair-currents on the ratio G(E(P))/G(M(P))

The effect of one-gluon-exchange (OGE) pair-currents on the ratio $\mu_p G_E^p/G_M^p$ for the proton is investigated within a nonrelativistic constituent quark model (CQM) starting from $SU(6) \times O(3)$ nucleon wave functions, but with relativistic corrections. We found that the OGE pair-currents are important to reproduce well the ratio $\mu_p G_E^p/G_M^p$. With the assumption that the OGE pair-currents are the driving mechanism for the violation of the scaling law we give a prediction for the ratio $\mu_n G_E^n/G_M^n$ of the neutron.Comment: 5 pages, 4 figure

The effect of interferon beta-1b treatment on MRI measures of cerebral atrophy in secondary progressive multiple sclerosis.

The recently completed European trial of interferon beta-1b (IFNβ-1b) in patients with secondary progressive multiple sclerosis (SP multiple sclerosis) has given an opportunity to assess the impact of treatment on cerebral atrophy using serial MRI. Unenhanced T1-weighted brain imaging was acquired in a subgroup of 95 patients from five of the European centres; imaging was performed at 6-month intervals from month 0 to month 36. A blinded observer measured cerebral volume on four contiguous 5 mm cerebral hemisphere slices at each time point, using an algorithm with a high level of reproducibility and automation. There was a significant and progressive reduction in cerebral volume in both placebo and treated groups, with a mean reduction of 3.9 and 2.9%, respectively, by month 36 (P = 0.34 between groups). Exploratory subgroup analyses indicated that patients without gadolinium (Gd) enhancement at the baseline had a greater reduction of cerebral volume in the placebo group (mean reduction at month 36: placebo 5.1%, IFNβ-1b 1.8%, P < 0.05) whereas those with Gd-enhancing lesions showed a trend to greater reduction of cerebral volume if the patient was on IFNβ-1b (placebo 2.6%, IFNβ-1b 3.7%; P > 0.05). These results are consistent with ongoing tissue loss in both arms of this study of secondary progressive multiple sclerosis. This finding is concordant with previous observations that disease progression, although delayed, is not halted by IFNβ. The different pattern seen in patients with and without baseline gadolinium enhancement suggests that part of the cerebral volume reduction observed in IFNβ-treated patients may be due to the anti-inflammatory/antioedematous effect of the drug. Longer periods of observation and larger groups of patients may be needed to detect the effects of treatment on cerebral atrophy in this population of patients with advanced diseas

A wider Europe? The view from Russia, Belarus and Ukraine

On the evidence of national surveys conducted between 2000 and 2006, there is a declining sense of European self-identity in the three Slavic post-Soviet republics of Russia, Belarus and Ukraine. Attitudes towards the European Union and the possibility of membership are broadly supportive, but with a substantial proportion who find it difficult to express a view, and substantial proportions are poorly informed in comparison with the general public in EU member or prospective member countries. Those who are better informed are more likely to favour EU membership and vice versa. Generally, socioeconomic characteristics (except for age and region) are relatively poor predictors of support for EU membership as compared with attitudinal variables. But ‘Europeanness’ should not be seen as a given, and much will depend on whether EU member countries emphasize what is common to east and west or establish ‘new dividing lines’ in place of those of the cold war

Microscopic theories of neutrino-^{12}C reactions

In view of the recent experiments on neutrino oscillations performed by the LSND and KARMEN collaborations as well as of future experiments, we present new theoretical results of the flux averaged $^{12}C(\nu_e,e^-)^{12}N$ and $^{12}C(\nu_{\mu},{\mu}^-)^{12}N$ cross sections. The approaches used are charge-exchange RPA, charge-exchange RPA among quasi-particles (QRPA) and the Shell Model. With a large-scale shell model calculation the exclusive cross sections are in nice agreement with the experimental values for both reactions. The inclusive cross section for $\nu_{\mu}$ coming from the decay-in-flight of $\pi^+$ is $15.2 \times 10^{-40} cm^2$ to be compared to the experimental value of $12.4 \pm 0.3 \pm 1.8 \times 10^{-40} cm^2$, while the one due to $\nu_{e}$ coming from the decay-at-rest of $\mu^+$ is $16.4 \times 10^{-42} cm^2$ which agrees within experimental error bars with the measured values. The shell model prediction for the decay-in-flight neutrino cross section is reduced compared to the RPA one. This is mainly due to the different kind of correlations taken into account in the calculation of the spin modes and partially due to the shell-model configuration basis which is not large enough, as we show using arguments based on sum-rules.Comment: 17 pages, latex, 5 figure

Melting transition of an Ising glass driven by magnetic field

The quantum critical behavior of the Ising glass in a magnetic field is investigated. We focus on the spin glass to paramagnet transition of the transverse degrees of freedom in the presence of finite longitudinal field. We use two complementary techniques, the Landau theory close to the T=0 transition and the exact diagonalization method for finite systems. This allows us to estimate the size of the critical region and characterize various crossover regimes. An unexpectedly small energy scale on the disordered side of the critical line is found, and its possible relevance to experiments on metallic glasses is briefly discussed.Comment: 4 pages, 3 figure

Assessment of the cortisol awakening response: expert consensus guidelines

The cortisol awakening response (CAR), the marked increase in cortisol secretion over the first 30–45 min after morning awakening, has been related to a wide range of psychosocial, physical and mental health parameters, making it a key variable for psychoneuroendocrinological research. The CAR is typically assessed from self-collection of saliva samples within the domestic setting. While this confers ecological validity, it lacks direct researcher oversight which can be problematic as the validity of CAR measurement critically relies on participants closely following a timed sampling schedule, beginning with the moment of awakening. Researchers assessing the CAR thus need to take important steps to maximize and monitor saliva sampling accuracy as well as consider a range of other relevant methodological factors. To promote best practice of future research in this field, the International Society of Psychoneuroendocrinology initiated an expert panel charged with (i) summarizing relevant evidence and collective experience on methodological factors affecting CAR assessment and (ii) formulating clear consensus guidelines for future research. The present report summarizes the results of this undertaking. Consensus guidelines are presented on central aspects of CAR assessment, including objective control of sampling accuracy/adherence, participant instructions, covariate accounting, sampling protocols, quantification strategies as well as reporting and interpreting of CAR data. Meeting these methodological standards in future research will create more powerful research designs, thus yielding more reliable and reproducible results and helping to further advance understanding in this evolving field of research