Effectiveness of adalimumab for rheumatoid arthritis in patients with a history of TNF-antagonist therapy in clinical practice

Objective. To evaluate the effectiveness and safety of adalimumab in patients with rheumatoid arthritis (RA) who previously discontinued tumour necrosis factor (TNF) antagonists for any reason in clinical practice. Methods. ReAct (Research in Active Rheumatoid Arthritis) was a large, open-label trial that enrolled adults with active RA who had previously been treated with traditional disease-modifying anti-rheumatic drugs or biological response modifiers. Patients selfadministered adalimumab 40 mg subcutaneously every other week for 12 weeks and were allowed to enter an optional long-term extension phase. Measures of adalimumab effectiveness included American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) response criteria, Disease Activity Score 28 (DAS28) and the Health Assessment Questionnaire Disability Index (HAQ DI). Results. Of 6610 patients, 899 had a history of etanercept and/or infliximab therapy; these patients experienced substantial clinical benefit from adalimumab treatment. At week 12, 60% of patients had an ACR20 and 33% had an ACR50 response; 76% had a moderate and 23% had a good EULAR response. In addition, 12% achieved a DAS28 < 2.6, indicating clinical remission, and 13% achieved a HAQ DI score < 0.5. The allergic adverse event rate, regardless of relationship to adalimumab, was 6.5/100-patient-years (PYs) in previously TNF antagonist-exposed patients and 4.3/100-PYs in TNF antagonist naive patients. A multiple regression analysis indicated no statistically significantly increased risk of serious infections in patients who received prior TNF antagonists compared with TNF antagonist naive patients. Conclusion. In typical clinical practice, adalimumab was effective and well-tolerated in patients with RA previously treated with etanercept and/or infliximab

Contemplative Science: An Insider's Prospectus

This chapter describes the potential far‐reaching consequences of contemplative higher education for the fields of science and medicine

Measuring errors and violations on the road: A bifactor modeling approach to the Driver Behavior Questionnaire

The Driver Behavior Questionnaire (DBQ) is a self-report measure of driving behavior that has been widely used over more than 20 years. Despite this wealth of evidence a number of questions remain, including understanding the correlation between its violations and errors sub-components, identifying how these components are related to crash involvement, and testing whether a DBQ based on a reduced number of items can be effective. We address these issues using a bifactor modeling approach to data drawn from the UK Cohort II longitudinal study of novice drivers. This dataset provides observations on 12,012 drivers with DBQ data collected at .5, 1, 2 and 3 years after passing their test. A bifactor model, including a general factor onto which all items loaded, and specific factors for ordinary violations, aggressive violations, slips and errors fitted the data better than correlated factors and second-order factor structures. A model based on only 12 items replicated this structure and produced factor scores that were highly correlated with the full model. The ordinary violations and general factor were significant independent predictors of crash involvement at 6 months after starting independent driving. The discussion considers the role of the general and specific factors in crash involvemen

Spatially resolved spectroscopy of planetary nebulae and their halos I. Five galactic disk objects

Strong mass loss off stars at the tip of the asymptotic giant branch (AGB) profoundly affects properties of these stars and their surroundings, including the subsequent planetary nebula (PN) stage. With this study we wanted to determine physical properties of mass loss by studying weakly emitting halos, focusing on objects in the galactic disk. Halos surround the, up to several thousand times, brighter central regions of PNe. Young halos, specifically, still contain information of the preceeding final mass loss stage on the AGB. In the observations we used the method of integral field spectroscopy with the PMAS instrument. This is the first committed study of halos of PNe that uses this technique. We improved our data analysis by a number of steps. In a study of the influence of scattered light we found that a moderate fraction of intensities in the inner halo originate in adjacent regions. As we combine line intensities of distant wavelengths, and because radial intensity gradients are steep, we corrected for effects of differential atmospheric refraction. In order to increase the signal-to-noise of weak emission lines we introduced a dedicated method to bin spectra of individual spatial elements. We also developed a general technique to subtract telluric lines - without using separate sky exposures. By these steps we avoided introducing errors of several thousand Kelvin to our temperature measurements in the halo. For IC3568 we detected a halo. For M2-2 we found a halo radius that is 2.5 times larger... (abridged)Comment: 27 pages, 29 figures, A&A (in press), Abridged abstract, Corrected and clarified various minor issues; the section on scattered light is significantly clarifie

Novice drivers’ individual trajectories of driver behavior over the first three years of driving

Identifying the changes in driving behavior that underlie the decrease in crash risk over the first few months of driving is key to efforts to reduce injury and fatality risk in novice drivers. This study represented a secondary data analysis of 1148 drivers who participated in the UK Cohort II study. The Driver Behavior Questionnaire was completed at 6 months and 1, 2 and 3 years after licensure. Linear latent growth models indicated significant increases across development in all four dimensions of aberrant driving behavior under scrutiny: aggressive violations, ordinary violations, errors and slips. Unconditional and conditional latent growth class analyses showed that the observed heterogeneity in individual trajectories was explained by the presence of multiple homogeneous groups of drivers, each exhibiting specific trajectories of aberrant driver behavior. Initial levels of aberrant driver behavior were important in identifying sub-groups of drivers. All classes showed positive slopes; there was no evidence of a group of drivers whose aberrant behavior decreased over time that might explain the decrease in crash involvement observed over this period. Male gender and younger age predicted membership of trajectories with higher levels of aberrant behavior. These findings highlight the importance of early intervention for improving road safety. We discuss the implications of our findings for understanding the behavioral underpinnings of the decrease in crash involvement observed in the early months of driving

The mimetic politics of lone-wolf terrorism

Written at a time of crisis in the project of social and political modernity, Fyodor Dostoevsky’s 1864 novel Notes from Underground offers an intriguing parallel for the twenty-first century lone-wolf; it portrays an abject, outcast, spiteful unnamed anti-hero boiling with rage, bitter with resentment and on the verge of radicalisation. A Girardian reading of the poetic truths contained in Dostoevsky’s work is able to provide important keys to explain the contemporary transformation from ‘fourth-wave’ religious terrorism to ‘fifth-wave’ lone-wolf terrorism. Such a reading argues that it is mimetic rivalry – rather than much-trumpeted forms of religious violence or cultural differences – that fuels the triangular relation between governments, terrorists and civilian victims at heart of terrorist acts. This approach is further able to blend social inquiry with an account of the individual, in fact anthropological, conditions of lone-wolf terrorism by tracing the globalisation of resentment and the individualisation of violence to the hyper-mimeticism characterising the globalisation of late modernity. Finally, a mimetic reading of ‘fifth-wave’ terrorism accounts for the turbulence of a global politics in which victimhood and scapegoating no longer have the ability to stabilise social order and warns against a future where violence proliferates and escalates unchecked

A Study of Time-Dependent CP-Violating Asymmetries and Flavor Oscillations in Neutral B Decays at the Upsilon(4S)

We present a measurement of time-dependent CP-violating asymmetries in neutral B meson decays collected with the BABAR detector at the PEP-II asymmetric-energy B Factory at the Stanford Linear Accelerator Center. The data sample consists of 29.7 ${\rm fb}^{-1}$ recorded at the $\Upsilon(4S)$ resonance and 3.9 ${\rm fb}^{-1}$ off-resonance. One of the neutral B mesons, which are produced in pairs at the $\Upsilon(4S)$, is fully reconstructed in the CP decay modes $J/\psi K^0_S$, $\psi(2S) K^0_S$, $\chi_{c1} K^0_S$, $J/\psi K^{*0}$ ($K^{*0}\to K^0_S\pi^0$) and $J/\psi K^0_L$, or in flavor-eigenstate modes involving $D^{(*)}\pi/\rho/a_1$ and $J/\psi K^{*0}$ ($K^{*0}\to K^+\pi^-$). The flavor of the other neutral B meson is tagged at the time of its decay, mainly with the charge of identified leptons and kaons. The proper time elapsed between the decays is determined by measuring the distance between the decay vertices. A maximum-likelihood fit to this flavor eigenstate sample finds $\Delta m_d = 0.516\pm 0.016 {\rm (stat)} \pm 0.010 {\rm (syst)} {\rm ps}^{-1}$. The value of the asymmetry amplitude $\sin2\beta$ is determined from a simultaneous maximum-likelihood fit to the time-difference distribution of the flavor-eigenstate sample and about 642 tagged $B^0$ decays in the CP-eigenstate modes. We find $\sin2\beta=0.59\pm 0.14 {\rm (stat)} \pm 0.05 {\rm (syst)}$, demonstrating that CP violation exists in the neutral B meson system. (abridged)Comment: 58 pages, 35 figures, submitted to Physical Review

Identifying beliefs underlying pre-drivers’ intentions to take risks: an application of the theory of planned behaviour

Novice motorists are at high crash risk during the first few months of driving. Risky behaviours such as speeding and driving while distracted are well-documented contributors to crash risk during this period. To reduce this public health burden, effective road safety interventions need to target the pre-driving period. We use the Theory of Planned Behaviour (TPB) to identify the pre-driver beliefs underlying intentions to drive over the speed limit (N = 77), and while over the legal alcohol limit (N = 72), talking on a hand-held mobile phone (N = 77) and feeling very tired (N = 68). The TPB explained between 41% and 69% of the variance in intentions to perform these behaviours. Attitudes were strong predictors of intentions for all behaviours. Subjective norms and perceived behavioural control were significant, though weaker, independent predictors of speeding and mobile phone use. Behavioural beliefs underlying these attitudes could be separated into those reflecting perceived disadvantages (e.g., speeding increases my risk of crash) and advantages (e.g., speeding gives me a thrill). Interventions that can make these beliefs safer in pre-drivers may reduce crash risk once independent driving has begun