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Marieke Krol,1 Gert de Voer,2 Ulrike Osowski3 1QuintilesIMS, Capelle aan den Ijssel, the Netherlands; 2Merck B.V., Schiphol-Rijk, the Netherlands; 3Merck KGaA, Darmstadt, Germany Purpose: Long-term treatment adherence among patients with multiple sclerosis (MS) is a general concern, with an established correlation with clinical efficacy. Closely monitoring patients’ treatment behavior may have a beneficial effect on adherence. This study assessed adherence, in daily life, to subcutaneous (sc) IFN beta-1a, self-administered using the RebiSmart® electronic injection device (the IFN beta-Ia autoinjector device), in patients with MS. Patients and methods: This was a retrospective observational study analyzing treatment adherence based on injection data, eg, injection date and dose, extracted from the IFN beta-Ia autoinjector devices collected from patients in Germany and the Netherlands. Results: Data recorded in the period from 2007 to 2012 by the IFN beta-Ia autoinjector devices from 1,682 (79.7% from Germany, 20.3% from the Netherlands) patients were analyzed. A mean of 94.8% of the multi-dose cartridges (containing sc IFN beta-1a for three injections) were used completely, indicating a low incidence of application errors and drug wastage. The mean adherence rate was 90.7% and 82.9% over the entire observation period (mean treatment duration: 150.1 weeks). Median adherence rates were similar between German and Dutch patients (97.9% vs 99.0%). Conclusion: In daily clinical practice, patients using the IFN beta-Ia autoinjector device were highly adherent to sc IFN beta-1a. The injection data stored electronically in the device may help patients to adhere to treatment regimens and, if viewed by physicians, promote discussion of adherence issues with patients. Keywords: multiple sclerosis, injection device, IFN beta-1a, observational study

The present study evaluates the microstructural features, mechanical properties, and wear characteristics of the newly developed hybrid composite of A356/ZrO2/Al2O3/SiC produced by compo-casting at 605±5 °C, 600 rpm for 15 minutes with less than 30% solid fraction in which Bi and Sn were added separately to the matrix before introducing reinforcements. FESEM micrographs and corresponding EDS illustrated the successful incorporation of particles in the matrix. Fine particles of ZrO2 were observed close to the coarse Al2O3, and SiC particles, along with Bi and Sn elements, were detected at the eutectic evolution region. The A356+Bi/Al2O3+ZrO2+SiC hybrid composite exhibited the lowest specific wear rate (1.642 x10-7 cm³/Nm) and friction coefficient (0.31) under applied loads of 5, 10, and 20 N, in line with the highest hardness (73.4 HBN). Analysis of the worn surfaces revealed that the wear mechanism is mostly adhesive in all synthesized composites, which changed to the combination of adhesive and abrasive mode in the case containing Bi and SiC. Inserting Bi not only leads to the refinement of eutectic Si but also enhances the adhesion between the matrix/particles and improves lubricity. This, in turn, reduces the wear rate and coefficient of friction, ultimately improving the performance of the hybrid composite. [ABSTRACT FROM AUTHOR]

This study presents the results of a broad intercomparison of a total of 15 global aerosol models within the AeroCom project. Each model is compared to observations related to desert dust aerosols, their direct radiative effect, and their impact on the biogeochemical cycle, i.e., aerosol optical depth (AOD) and dust deposition. Additional com parisons to Angstrom exponent (AE), coarse mode AOD and dust surface concentrations are included to extend the assessment of model performance and to identify common biases present in models. These data comprise a benchmark dataset that is proposed for model inspection and future dust model development. There are large differences among the global models that simulate the dust cycle and its impact on climate. In general, models simulate the climatology of vertically integrated parameters (AOD and AE) within a factor of two whereas the total deposition and surface concentration are reproduced within a factor of 10. In addition, smaller mean normalized bias and root mean square errors are obtained for the climatology of AOD and AE than for total deposition and surface concentration. Characteristics of the datasets used and their uncertainties may influence these differences. Large uncertainties still exist with respect to the deposition fluxes in the southern oceans. Further measurements and model studies are necessary to assess the general model performance to reproduce dust deposition in ocean regions sensible to iron contributions. Models overestimate the wet deposition in regions dominated by dry deposition. They generally simulate more realistic surface concentration at stations downwind of the main sources than at remote ones. Most models simulate the gradient in AOD and AE between the different dusty regions. However the seasonality and magnitude of both variables is better simulated at African stations than Middle East ones. The models simulate the offshore transport of West Africa throughout the year but they overestimate the AOD and they transport too fine particles. The models also reproduce the dust transport across the Atlantic in the summer in terms of both AOD and AE but not so well in winter-spring nor the southward displacement of the dust cloud that is responsible of the dust transport into South America. Based on the dependency of AOD on aerosol burden and size distribution we use model bias with respect to AOD and AE to infer the bias of the dust emissions in Africa and the Middle East. According to this analysis we suggest that a range of possible emissions for North Africa is 400 to 2200 Tg yr(-1) and in the Middle East 26 to 526 Tg yr(-1)

We present an estimate of net CO2 exchange between the terrestrial biosphere and the atmosphere across North America for every week in the period 2000 through 2005. This estimate is derived from a set of 28,000 CO2 mole fraction observations in the global atmosphere that are fed into a state-of-the-art data assimilation system for CO2 called CarbonTracker. By design, the surface fluxes produced in CarbonTracker are consistent with the recent history of CO2 in the atmosphere and provide constraints on the net carbon flux independent from national inventories derived from accounting efforts. We find the North American terrestrial biosphere to have absorbed −0.65 PgC/yr (1 petagram = 1015 g; negative signs are used for carbon sinks) averaged over the period studied, partly offsetting the estimated 1.85 PgC/yr release by fossil fuel burning and cement manufacturing. Uncertainty on this estimate is derived from a set of sensitivity experiments and places the sink within a range of −0.4 to −1.0 PgC/yr. The estimated sink is located mainly in the deciduous forests along the East Coast (32%) and the boreal coniferous forests (22%). Terrestrial uptake fell to −0.32 PgC/yr during the large-scale drought of 2002, suggesting sensitivity of the contemporary carbon sinks to climate extremes. CarbonTracker results are in excellent agreement with a wide collection of carbon inventories that form the basis of the first North American State of the Carbon Cycle Report (SOCCR), to be released in 2007.

We analyze present-day and future carbon monoxide (CO) simulations in 26 state-of-the-art atmospheric chemistry models run to study future air quality and climate change. In comparison with near-global satellite observations from the MOPITT instrument and local surface measurements, the models show large underestimates of Northern Hemisphere (NH) extratropical CO, while typically performing reasonably well elsewhere. The results suggest that year-round emissions, probably from fossil fuel burning in east Asia and seasonal biomass burning emissions in south-central Africa, are greatly underestimated in current inventories such as IIASA and EDGAR3.2. Variability among models is large, likely resulting primarily from intermodel differences in representations and emissions of nonmethane volatile organic compounds (NMVOCs) and in hydrologic cycles, which affect OH and soluble hydrocarbon intermediates. Global mean projections of the 2030 CO response to emissions changes are quite robust. Global mean midtropospheric (500 hPa) CO increases by 12.6 ± 3.5 ppbv (16%) for the high-emissions (A2) scenario, by 1.7 ± 1.8 ppbv (2%) for the midrange (CLE) scenario, and decreases by 8.1 ± 2.3 ppbv (11%) for the low-emissions (MFR) scenario. Projected 2030 climate changes decrease global 500 hPa CO by 1.4 ± 1.4 ppbv. Local changes can be much larger. In response to climate change, substantial effects are seen in the tropics, but intermodel variability is quite large. The regional CO responses to emissions changes are robust across models, however. These range from decreases of 10–20 ppbv over much of the industrialized NH for the CLE scenario to CO increases worldwide and year-round under A2, with the largest changes over central Africa (20–30 ppbv), southern Brazil (20–35 ppbv) and south and east Asia (30–70 ppbv). The trajectory of future emissions thus has the potential to profoundly affect air quality over most of the world's populated areas.

We present a systematic comparison of tropospheric NO2 from 17 global atmospheric chemistry models with three state-of-the-art retrievals from the Global Ozone Monitoring Experiment (GOME) for the year 2000. The models used constant anthropogenic emissions from IIASA/EDGAR3.2 and monthly emissions from biomass burning based on the 1997–2002 average carbon emissions from the Global Fire Emissions Database (GFED). Model output is analyzed at 10:30 local time, close to the overpass time of the ERS-2 satellite, and collocated with the measurements to account for sampling biases due to incomplete spatiotemporal coverage of the instrument. We assessed the importance of different contributions to the sampling bias: correlations on seasonal time scale give rise to a positive bias of 30–50% in the retrieved annual means over regions dominated by emissions from biomass burning. Over the industrial regions of the eastern United States, Europe and eastern China the retrieved annual means have a negative bias with significant contributions (between –25% and +10% of the NO2 column) resulting from correlations on time scales from a day to a month. We present global maps of modeled and retrieved annual mean NO2 column densities, together with the corresponding ensemble means and standard deviations for models and retrievals. The spatial correlation between the individual models and retrievals are high, typically in the range 0.81–0.93 after smoothing the data to a common resolution. On average the models underestimate the retrievals in industrial regions, especially over eastern China and over the Highveld region of South Africa, and overestimate the retrievals in regions dominated by biomass burning during the dry season. The discrepancy over South America south of the Amazon disappears when we use the GFED emissions specific to the year 2000. The seasonal cycle is analyzed in detail for eight different continental regions. Over regions dominated by biomass burning, the timing of the seasonal cycle is generally well reproduced by the models. However, over Central Africa south of the Equator the models peak one to two months earlier than the retrievals. We further evaluate a recent proposal to reduce the NOx emission factors for savanna fires by 40% and find that this leads to an improvement of the amplitude of the seasonal cycle over the biomass burning regions of Northern and Central Africa. In these regions the models tend to underestimate the retrievals during the wet season, suggesting that the soil emissions are higher than assumed in the models. In general, the discrepancies between models and retrievals cannot be explained by a priori profile assumptions made in the retrievals, neither by diurnal variations in anthropogenic emissions, which lead to a marginal reduction of the NO2 abundance at 10:30 local time (by 2.5–4.1% over Europe). Overall, there are significant differences among the various models and, in particular, among the three retrievals. The discrepancies among the retrievals (10–50% in the annual mean over polluted regions) indicate that the previously estimated retrieval uncertainties have a large systematic component. Our findings imply that top-down estimations of NOx emissions from satellite retrievals of tropospheric NO2 are strongly dependent on the choice of model and retrieval.

Department of Cancer Biology, Institute of Biology, Warsaw University of Life Sciences, Warsaw, Poland Glioblastoma, the most common and aggressive type of brain tumor in adults, poses significant challenges in terms of treatment. Conventional approaches including surgery, chemotherapy, and radiotherapy have yielded limited success, with a median survival of approximately 15 months. However, extensive research into the biology of glioblastoma has identified molecular targets that can be exploited by newly developed drugs, leading to the emergence of precise personalized therapies. Several innovative treatment strategies are currently under development, aiming to enhance effectiveness while minimizing side effects. Clinical trials are underway to evaluate the efficacy of monoclonal antibodies that target glioblastoma cells, either by blocking specific receptors or by modifying molecular interactions that impede cell proliferation. Another promising avenue involves the use of oncolytic viruses designed to selectively infect glioblastoma cells. Additionally, the review explores the utilization of nanocarriers capable of surmounting the formidable obstacle of the blood-brain barrier, enabling efficient drug delivery. Cell therapies represent another promising approach, with dendritic cells, chimeric antigen receptor-T cells, and macrophages emerging as potential treatment modalities. By summarizing recent advances in targeted therapies against glioblastoma, this review aims to provide a comprehensive overview of ongoing efforts to discover effective and safe methods for treating glioblastoma patients. The ultimate goal is to improve patient outcomes and transform the landscape of glioblastoma treatment. [ABSTRACT FROM AUTHOR]

Observations of methyl chloroform combined with an atmospheric transport model predict a Northern to Southern Hemisphere hydroxyl ratio of slightly less than 1, whereas commonly used atmospheric chemistry models predict ratios 15-45% higher. The north-south distribution of atmospheric OH The hydroxyl radical is an important atmospheric oxidant, but our knowledge of its global distribution remains imprecise, with estimates for the ratio of Northern Hemisphere to Southern Hemisphere hydroxyl radical concentration varying from 0.85 to 1.4. These authors use a three-dimensional chemistry-transport model that has been well validated for interhemispheric transport using sulphur hexafluoride measurements, to obtain an interhemispheric hydroxyl radical ratio of 0.97[plus or minus]0.12. This information can help improve our understanding of the fate of atmospheric pollutants and greenhouse gases. The hydroxyl radical (OH) is a key oxidant involved in the removal of air pollutants and greenhouse gases from the atmosphere.sup.1,2,3. The ratio of Northern Hemispheric to Southern Hemispheric (NH/SH) OH concentration is important for our understanding of emission estimates of atmospheric species such as nitrogen oxides and methane.sup.4,5,6. It remains poorly constrained, however, with a range of estimates from 0.85 to 1.4 (refs 4, 7,8,9,10). Here we determine the NH/SH ratio of OH with the help of methyl chloroform data (a proxy for OH concentrations) and an atmospheric transport model that accurately describes interhemispheric transport and modelled emissions. We find that for the years 2004-2011 the model predicts an annual mean NH-SH gradient of methyl chloroform that is a tight linear function of the modelled NH/SH ratio in annual mean OH. We estimate a NH/SH OH ratio of 0.97 [plus or minus] 0.12 during this time period by optimizing global total emissions and mean OH abundance to fit methyl chloroform data from two surface-measurement networks and aircraft campaigns.sup.11,12,13. Our findings suggest that top-down emission estimates of reactive species such as nitrogen oxides in key emitting countries in the NH that are based on a NH/SH OH ratio larger than 1 may be overestimated., Author(s): P. K. Patra [sup.1] [sup.2] , M. C. Krol [sup.3] , S. A. Montzka [sup.4] , T. Arnold [sup.5] , E. L. Atlas [sup.6] , B. R. Lintner [sup.7] [...]

Exploring the non-Hermitian properties of semiconductor materials for optical applications is at the forefront of photonic research. However, the selection of appropriate systems to implement such photonic devices remains a topic of debate. In this work, we demonstrate that a perovskite crystal, characterized by its easy and low-cost manufacturing, when placed between two distributed Bragg reflectors with an air gap, can form a natural double microcavity. This construction shows promising properties for the realisation of novel, tunable non-Hermitian photonic devices through strong light–matter coupling. We reveal that such a system exhibits double-coupled polariton modes with dispersion including multiple inflection points. Owing to its non-Hermiticity, our system exhibits nonreciprocal properties and allows for the observation of exceptional points. Our experimental studies are in agreement with the theoretical analysis based on coupled mode theory and calculations based on transfer matrix method.

The exponential stability of evolution differential equations obtained on the basis of heat conduction equations is studied. To determine the boundaries of stochastic stability of the solution of these equations, we use the method of construction of a Lyapunov functional., UDC 517.983.54 Introduction The work is devoted to the use of the Lyapunov method for the derivation of criteria of almost sure stability of Ito-type nonlinear equations generated by equations [...]

Optoelectronic and spinoptronic technologies benefit from flexible and tunable coherent light sources combining the best properties of nano- and material-engineering to achieve favorable properties such as chiral lasing and low threshold nonlinearities. In this work we demonstrate an electrically wavelength- and polarization-tunable room temperature polariton laser due to emerging photonic spin–orbit coupling. For this purpose, we design an optical cavity filled with both birefringent nematic liquid crystal and an inorganic perovskite. Our versatile growth method of single CsPbBr3 inorganic perovskite crystals in polymer templates allows us to reach strong light–matter coupling and pump-induced condensation of exciton–polaritons resulting in coherent emission of light. The sensitivity of the liquid crystal to external voltage permits electrical tuning of the condensate energy across 7 nm; its threshold power, allowing us to electrically switch it on and off; and its state of polarization sweeping from linear to locally tilted circularly polarized emission.