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Introduction The open-label Rapid Onset and Sustained Efficacy (ROSE) study was designed to compare a once-yearly intravenous (iv) dose of zoledronic acid with a once-weekly oral dose of alendronate with respect to markers of bone turnover in approximately 600 postmenopausal women in Germany. Methods Levels of N-telopeptide of collagen type I (NTx) and procollagen 1 C terminal extension peptide (P1NP) were assessed during the study. The primary objective was to assess if zoledronic acid was superior to alendronate in reducing serum NTx levels after 12 months’ treatment. Results A significantly greater reduction in NTx levels from baseline to month 12 (as determined by the area under the curve) was observed in patients treated with zoledronic acid ( n  = 408) versus those receiving alendronate ( n  = 196; 0.282 ng/mL vs. 0.270 ng/mL; P  = 0.012). The reduction in levels of P1NP after 1 year was also significantly greater in patients treated with zoledronic acid compared with those receiving alendronate (28.21 vs. 25.53 ng/mL; P  = 0.0024). The overall incidence of adverse events was similar between groups; both treatments were generally well tolerated. Although post-dose symptoms, including the incidence of influenza-like symptoms, were higher with zoledronic acid than alendronate initially, the incidence was similar between groups from days 4–360. Gastrointestinal symptoms were more frequent with alendronate than zoledronic acid throughout the study. Conclusion In this study, once-yearly iv zoledronic acid provided a greater and faster reduction in the levels of NTx and P1NP versus once-weekly oral alendronate.

Summary The ROSE study compared annual infusion with zoledronic acid and weekly generic alendronate. No significant differences in quality of life or health status between treatment groups were observed. Adherence to alendronate during the study was high, with 80.9% of patients achieving adequate adherence. Introduction A secondary analysis to evaluate quality of life, health status, adherence to alendronate and therapy preference in postmenopausal women with low bone mass who received treatment with zoledronic acid or alendronate was conducted. Methods Postmenopausal women with low bone mass were randomised 2:1 to receive an annual infusion of zoledronic acid or weekly oral generic alendronate in this open-label, multicentre study. Changes in quality of life and health status were assessed using questionnaires at baseline and month 12. Adherence to alendronate was assessed by the investigator and/or study personnel, and subjective therapy preference was assessed using a questionnaire at month 12. Results Patients were randomised to zoledronic acid ( n  = 408) and alendronate ( n  = 191). Overall, there were no significant differences in quality of life between zoledronic acid and alendronate. However, improvements in quality of life with zoledronic acid versus alendronate could be detected by posthoc analysis in patients with previous fractures. There were no significant differences in health status between patients receiving zoledronic acid or alendronate. Adherence to alendronate during the study was high, with 80.9% of patients achieving adequate adherence. A total of 81% of patients who had received zoledronic acid indicated that they would prefer to continue with that treatment, and 43% of the patients who received oral alendronate would like to switch to zoledronic acid. Conclusions There were no significant differences in quality of life between patients receiving zoledronic acid or alendronate.

Background Current labeling requires rheumatoid arthritis (RA) patients receiving golimumab (GLM) to receive concomitant methotrexate (MTX), and most studies have investigated GLM on the background of MTX treatment. Limited information is available regarding GLM as add-on therapy to disease-modifying antirheumatic drugs (DMARD) such as leflunomide (LEF). Objectives To evaluate the effectiveness and safety of GLM as add-on therapy in biologic-naïve patients with RA receiving concomitant MTX or LEF in clinical settings. Methods GO-MORE was an open-label, multinational, prospective study in biologic-naïve patients with active RA (DAS28-ESR ≥3.2). Patients received 50-mg SC GLM once monthly for 6 months. The primary outcome was the percentage of patients with good or moderate EULAR DAS28-ESR response at 6 months. Remission (DAS28-ESR <2.6) and minimal or no functional impairment (Health Assessment Questionnaire-Disability Index [HAQ-DI] ≤0.5) were also assessed. Treatment effects were evaluated with chi-square tests. Post hoc analyses evaluated outcomes in patients who received concomitant MTX or concomitant LEF. Results Patients receiving GLM with concomitant MTX (alone or with other DMARDs) or GLM with concomitant LEF (with no other DMARDs) accounted for 81.2% (2663/3280) and 9.3% (303/3270) of the total study population, respectively. The concomitant MTX and LEF subgroups had comparable baseline disease characteristics, including mean DAS28-ESR (5.43 and 5.25, respectively), DAS28-CRP (5.99 and 5.79, respectively), and HAQ-DI (1.44 and 1.36, respectively). These values were similar to the baseline means of the overall population. At month 6, similarly high EULAR response rates were noted in the GLM with concomitant MTX (85%) and GLM with concomitant LEF (81%) subgroups (Table). Similar EULAR responses were also observed in patients receiving GLM+MTX without other DMARDs (83%) and GLM+MTX+LEF without other DMARDs (78%). Serious treatment-emergent adverse events (TEAEs) occurred in 5.1% (136/2656) of the concomitant MTX subgroup and 6.8% (21/309) of the LEF subgroup. There were 5 (0.19%) and 0 deaths in the concomitant MTX and LEF subgroups, respectively. Conclusions Overall, add-on SC GLM therapy was highly efficacious with concomitant MTX or LEF in patients with active RA despite DMARD therapy. Safety profiles were consistent with those of previous studies of GLM. Disclosure of Interest J. Wollenhaupt Consultant for: Abbott, Biotest, BMS, Chugai, MSD, Medac, Merck, MSD, Pfizer, Roche, and UCB., Speakers bureau: Abbott, Biotest, BMS, Chugai, MSD, Medac, Merck, MSD, Pfizer, Roche, and UCB., A. Alonso-Ruiz: None Declared, W. Spieler: None Declared, J. Beier: None Declared, J. Molina: None Declared, R. Yao Employee of: Merck, M. Govoni Employee of: Merck, N. Vastesaeger Employee of: Merck, H. Weng Employee of: Merck

This randomized, placebo-controlled study assessed the safety, tolerability, and immunogenicity of live virus zoster vaccine (ZV) in individuals receiving chronic/maintenance systemic corticosteroid therapy (daily dose equivalent of 5–20mg prednisone) for ≥2 weeks prior to vaccination and ≥6 weeks postvaccination. Subjects were followed for adverse experiences (AEs), exposure to varicella or herpes zoster (HZ), or development of varicella/varicella-like or HZ/HZ-like rashes for 42 days postvaccination (primary safety follow-up period) and for serious AEs (SAEs) through Day 182 postvaccination (secondary follow-up period). Varicella-zoster virus (VZV) antibody titers by glycoprotein enzyme-linked immunosorbent assay (gpELISA) were measured at baseline and at Week 6 postvaccination. The proportions of subjects reporting systemic AEs and SAEs were similar in both groups. A higher percentage of subjects reported injection-site AEs in the ZV group (21.5%) than in the placebo group (12.1%). One SAE of ophthalmic HZ (onset Day 16 postvaccination) was reported in the ZV group and deemed vaccine-related by the study investigator; however, PCR testing confirmed the presence of wild-type (not vaccine strain) VZV. Geometric mean titer (GMT) at 6 weeks postvaccination was higher for ZV recipients than placebo recipients, with estimated geometric mean fold rises (GMFR) of 2.3 (CI: 2.0, 2.7) and 1.1 (CI: 1.0, 1.2) respectfully. In adults ≥60 years old on chronic/maintenance corticosteroids, ZV was generally well tolerated and immunogenic. The VZV-specific gpELISA antibody GMT at 6 weeks postvaccination and the GMFR from baseline to 6 weeks postvaccination were higher in the ZV group than in the placebo group.

THE use of opal glass in Photography is of quite recent date, and the quantity required for experimental purposes was so small that no care was taken in its manufacture to adapt it to this special purpose. Since the introduction of the photo miniature, however, the faults of the article as now made, have been seriously felt by all...

The South Pole Telescope (SPT) is a 10 m diameter, wide-field, offset Gregorian telescope with a 966 pixel, multicolor, millimeter-wave, bolometer camera. It is located at the Amundsen-Scott South Pole station in Antarctica. The design of the SPT emphasizes careful control of spillover and scattering, to minimize noise and false signals due to ground pickup. The key initial project is a large-area survey at wavelengths of 3, 2, and 1.3 mm, to detect clusters of galaxies via the Sunyaev-Zel’dovich effect and to measure the small-scale angular power spectrum of the cosmic microwave background (CMB). The data will be used to characterize the primordial matter power spectrum and to place constraints on the equation of state of dark energy. A second-generation camera will measure the polarization of the CMB, potentially leading to constraints on the neutrino mass and the energy scale of inflation.

Estimating the impact of different sources of uncertainty along the modelling chain is an important skill graduates are expected to have. Broadly speaking, educators can cover uncertainty in hydrological modelling by differentiating uncertainty in data, model parameters and model structure. This provides students with insights on the impact of uncertainties on modelling results and thus on the usability of the acquired model simulations for decision making. A survey among teachers in the Earth and environmental sciences showed that model structural uncertainty is the least represented uncertainty group in teaching. This paper introduces a computational exercise that introduces students to the basics of model structure uncertainty through two ready-to-use modelling experiments. These experiments require either Matlab or Octave, and use the open-source Modular Assessment of Rainfall-Runoff Models Toolbox (MARRMoT) and the open-source Catchment Attributes and Meteorology for Large-sample Studies (CAMELS) data set. The exercise is short and can easily be integrated into an existing hydrological curriculum, with only a limited time investment needed to introduce the topic of model structure uncertainty and run the exercise. Two trial applications at the Technische Universität Dresden (Germany) showed that the exercise can be completed in two afternoons or four 90 min sessions and that the provided setup effectively transfers the intended insights about model structure uncertainty.

The ability to accurately predict streamflow underpins decisions in water management, flood prevention, and sectoral planning. Traditional approaches for streamflow prediction often rely on a single model, thereby overlooking potential benefits from using multiple models. To address this limitation, this study explores alternative methods that select and combine multiple models to enhance streamflow simulations. Specifically, we assess the performance of multi-model mosaic methods that assign a single model to each catchment, and multi-model combination methods that merge multiple models using static or dynamic weighting schemes. The Framework for Understanding Structural Errors (FUSE) is used to create an ensemble of 78 hydrological models, which were applied to 544 catchments from the CAMELS dataset across the contiguous United States. Each of the 78 models is calibrated utilizing a composite objective function, calculated as the average of a high-flow and a low-flow performance metric, to cover a wide range of streamflow conditions. Based on our selection of lumped FUSE models, the results show that a carefully chosen single model from a larger ensemble can closely approach the performance of more complex multi-model strategies. Among the multi-model approaches, the combination and mosaic methods show broadly similar overall skill, although the combination approaches deliver slightly higher performance and lower sampling uncertainty. However, per-catchment differences persist, indicating that no single multi-model strategy dominates everywhere. This heterogeneity in performance makes it difficult to determine a priori which multi-model method will best represent streamflow in a given catchment.