Switching to Biosimilars in Inflammatory Rheumatic Conditions: Current Knowledge

Biosimilars are more affordable versions of previously approved biopharmaceuticals that are designed to reduce healthcare expenditure and increase patient access to this therapeutic class. To achieve their economic potential, many European countries have started to switch patients from reference drugs to biosimilars. The purpose of this article is to provide a comprehensive perspective on the biosimilar switching controversy, to assess interchangeability regulation and switching policies, and to review current evidence on switching and immunogenicity in the context of inflammatory rheumatic conditions. Patients and physicians feel uncertain about switching highly complex and difficult-to-replicate biosimilars of monoclonal antibodies due to a theoretical risk of increased immunogenicity, especially in extrapolated indications and in a multiple switch scenario involving various biosimilars. However, past experience with smaller biosimilars (somatropin, filgrastim, epoetin), the high standards required for approval of biosimilars of monoclonal antibodies in the European market, and current evidence on switching to infliximab and etanercept biosimilars (especially CT-P13 and SB4) are reassuring. Furthermore, no increased immunogenicity has been reported after switching to biosimilars. Decisions on switching and interchangeability are not covered by the European Medical Agency (EMA) guidelines and are left to individual European states, as opposed to the U.S. Food and Drug Administration (FDA), which has set standards to assess interchangeability. In summary, current knowledge is in favour of switching to biosimilars but the authors consider that this should be a physician-led decision with the active contribution of patients and hospital pharmacists to the pharmacovigilance chain

Germination temperature sensitivity differs between co-occurring tree species and climate origins resulting in contrasting vulnerability to global warming

Climate change is shifting temperatures from historical patterns, globally impacting forest composition and resilience. Seed germination is temperature-sensitive, making the persistence of populations and colonization of available habitats vulnerable to warming. This study assessed germination response to temperature in foundation trees in south-western Australia's Mediterranean-type climate forests (Eucalyptus marginata (jarrah) and Corymbia calophylla (marri)) to estimate the thermal niche and vulnerability among populations. Seeds from the species' entire distribution were collected from 12 co-occurring populations. Germination thermal niche was investigated using a thermal gradient plate (5–40°C). Five constant temperatures between 9 and 33°C were used to test how the germination niche (1) differs between species, (2) varies among populations, and (3) relates to the climate of origin. Germination response differed among species; jarrah had a lower optimal temperature and thermal limit than marri (To 15.3°C, 21.2°C; ED50 23.4°C, 31°C, respectively). The thermal limit for germination differed among populations within both species, yet only marri showed evidence for adaptation to thermal origins. While marri has the capacity for germination at higher thermal temperatures, jarrah is more vulnerable to global warming exceeding safety margins. This discrepancy is predicted to alter species distributions and forest composition in the future

Stable oxygen isotope and flux partitioning demonstrates understory of an oak savanna contributes up to half of ecosystem carbon and water exchange

Semi-arid ecosystems contribute about 40% to global net primary production (GPP) even though water is a major factor limiting carbon uptake. Evapotranspiration (ET) accounts for up to 95% of the water loss and in addition, vegetation can also mitigate drought effects by altering soil water distribution. Hence, partitioning of carbon and water fluxes between the soil and vegetation components is crucial to gain mechanistic understanding of vegetation effects on carbon and water cycling. However, the possible impact of herbaceous vegetation in savanna type ecosystems is often overlooked. Therefore, we aimed at quantifying understory vegetation effects on the water balance and productivity of a Mediterranean oak savanna. ET and net ecosystem CO2 exchange (NEE) were partitioned based on flux and stable oxygen isotope measurements and also rain infiltration was estimated. The understory vegetation contributed importantly to total ecosystem ET and GPP with a maximum of 43 and 51%, respectively. It reached water-use efficiencies (WUE; ratio of carbon gain by water loss) similar to cork-oak trees. The understory vegetation inhibited soil evaporation (E) and, although E was large during wet periods, it did not diminish WUE during water-limited times. The understory strongly increased soil water infiltration, specifically following major rain events. At the same time, the understory itself was vulnerable to drought, which led to an earlier senescence of the understory growing under trees as compared to open areas, due to competition for water. Thus, beneficial understory effects are dominant and contribute to the resilience of this ecosystem. At the same time the vulnerability of the understory to drought suggests that future climate change scenarios for the Mediterranean basin threaten understory development. This in turn will very likely diminish beneficial understory effects like infiltration and ground water recharge and therefore ecosystem resilience to drought

Signatures of natural selection in a foundation tree along Mediterranean climatic gradients

Temperature and precipitation regimes are rapidly changing, resulting in forest dieback and extinction events, particularly in Mediterranean-type climates (MTC). Forest management that enhance forests’ resilience is urgently required, however adaptation to climates in heterogeneous landscapes with multiple selection pressures is complex. For widespread trees in MTC we hypothesized that: patterns of local adaptation are associated with climate; precipitation is a stronger factor of adaptation than temperature; functionally related genes show similar signatures of adaptation; and adaptive variants are independently sorting across the landscape. We sampled 28 populations across the geographic distribution of Eucalyptus marginata (jarrah), in South-west Western Australia, and obtained 13,534 independent single nucleotide polymorphic (SNP) markers across the genome. Three genotype-association analyses that employ different ways of correcting population structure were used to identify putatively adapted SNPs associated with independent climate variables. While overall levels of population differentiation were low (FST = 0.04), environmental association analyses found a total of 2336 unique SNPs associated with temperature and precipitation variables, with 1440 SNPs annotated to genic regions. Considerable allelic turnover was identified for SNPs associated with temperature seasonality and mean precipitation of the warmest quarter, suggesting that both temperature and precipitation are important factors in adaptation. SNPs with similar gene functions had analogous allelic turnover along climate gradients, while SNPs among temperature and precipitation variables had uncorrelated patterns of adaptation. These contrasting patterns provide evidence that there may be standing genomic variation adapted to current climate gradients, providing the basis for adaptive management strategies to bolster forest resilience in the future

Electro-Hydraulic Transient Regimes in Isolated Pumps Working as Turbines with Self-Excited Induction Generators

[EN] The use of pumps working as turbines (PATs) is a sustainable technical measure that contributes to the improvement of energy efficiency in water systems. However, its performance analysis in off-grid recovery systems is a complex task that must consider both hydraulic (PAT) and electrical machines (typically a self-excited induction generator-SEIG). Aside from several kinds of research that analyze the PAT-SEIG behavior under steady-state constant hydraulic and electrical conditions, this research focuses on the analysis of PAT-SEIG transient regimes, by analyzing their variation when a sudden change occurs in the hydraulic or electrical components. Analytical models were developed to represent the operation of SEIG, PAT, and the PAT-SEIG coupled system. Hydraulic and electromechanical experimental tests validated these models. An excellent fit was obtained when analytical and experimental values were compared. With these models, the impact on the operation of the PAT-SEIG system was examined when sudden change occurred in the excitation capacitances, resistive loads, or recovered head. With a sudden increase of resistive load, the hydraulic power and SEIG stator current remain almost constant. However, there is an increase of SEIG reactive power, decreasing the PAT-SEIG efficiency. Also, with a sudden increase of SEIG capacitors or PAT hydraulic head, the SEIG stator current increases once and not again, while PAT-SEIG efficiency decreases, but the induction generator can be overloaded. The development of this research is key to the advancement of future models which can analyze the coupling of micro-hydropower solutions.This research received some support from the project REDAWN (Reducing Energy Dependency in Atlantic Area Water Networks) EAPA_198/2016 from INTERREG ATLANTIC AREA.Madeira, FC.; Fernandes, JFP.; Pérez-Sánchez, M.; López Jiménez, PA.; Ramos, HM.; Costa Branco, PJ. (2020). Electro-Hydraulic Transient Regimes in Isolated Pumps Working as Turbines with Self-Excited Induction Generators. Energies. 13(17):1-23. https://doi.org/10.3390/en13174521S1231317Postacchini, M., Darvini, G., Finizio, F., Pelagalli, L., Soldini, L., & Di Giuseppe, E. (2020). Hydropower Generation Through Pump as Turbine: Experimental Study and Potential Application to Small-Scale WDN. Water, 12(4), 958. doi:10.3390/w12040958Capelo, B., Pérez-Sánchez, M., Fernandes, J. F. P., Ramos, H. M., López-Jiménez, P. A., & Branco, P. J. C. (2017). Electrical behaviour of the pump working as turbine in off grid operation. Applied Energy, 208, 302-311. doi:10.1016/j.apenergy.2017.10.039Fecarotta, O., Aricò, C., Carravetta, A., Martino, R., & Ramos, H. M. (2014). Hydropower Potential in Water Distribution Networks: Pressure Control by PATs. Water Resources Management, 29(3), 699-714. doi:10.1007/s11269-014-0836-3Ramos, H., & Borga, A. (1999). Pumps as turbines: an unconventional solution to energy production. Urban Water, 1(3), 261-263. doi:10.1016/s1462-0758(00)00016-9Fernandes, J. F. P., Pérez-Sánchez, M., da Silva, F. F., López-Jiménez, P. A., Ramos, H. M., & Branco, P. J. C. (2019). Optimal energy efficiency of isolated PAT systems by SEIG excitation tuning. Energy Conversion and Management, 183, 391-405. doi:10.1016/j.enconman.2019.01.016Yi, Y., Zhang, Z., Chen, D., Zhou, R., Patelli, E., & Tolo, S. (2017). State feedback predictive control for nonlinear hydro-turbine governing system. Journal of Vibration and Control, 107754631774001. doi:10.1177/1077546317740013Khan, M. F., & Khan, M. R. (2016). Analysis of voltage build-up and speed disturbance ride through capability of a self-excited induction generator for renewable energy application. International Journal of Power and Energy Conversion, 7(2), 157. doi:10.1504/ijpec.2016.076521Han, Y., & Tan, L. (2020). Dynamic mode decomposition and reconstruction of tip leakage vortex in a mixed flow pump as turbine at pump mode. Renewable Energy, 155, 725-734. doi:10.1016/j.renene.2020.03.142Pérez-Sánchez, M., Sánchez-Romero, F. J., López-Jiménez, P. A., & Ramos, H. M. (2018). PATs selection towards sustainability in irrigation networks: Simulated annealing as a water management tool. Renewable Energy, 116, 234-249. doi:10.1016/j.renene.2017.09.060Pérez-Sánchez, M., López-Jiménez, P., & Ramos, H. (2018). PATs Operating in Water Networks under Unsteady Flow Conditions: Control Valve Manoeuvre and Overspeed Effect. Water, 10(4), 529. doi:10.3390/w1004052

Monolithic porous carbon materials prepared from polyurethane foam templates

Monolithic carbon foams with hierarchical porosity were prepared from polyurethane templates and resol precursors. Mesoporosity was achieved through the use of soft templating with surfactant Pluronic F127, and macroporosity from the polyurethane foams was retained. Conditions to obtain high porosity materials were optimized. The best materials have high specific surface areas (380 and 582 m(2) g(-1), respectively) and high electrical conductivity, which make them good candidates for supports in sensors. These materials showed an almost linear dependence between the potential and the pH of aqueous solutions

Loss of Population Levels of Immunity to Malaria as a Result of Exposure-Reducing Interventions: Consequences for Interpretation of Disease Trends

BACKGROUND: The persistence of malaria as an endemic infection and one of the major causes of childhood death in most parts of Africa has lead to a radical new call for a global effort towards eradication. With the deployment of a highly effective vaccine still some years away, there has been an increased focus on interventions which reduce exposure to infection in the individual and -by reducing onward transmission-at the population level. The development of appropriate monitoring of these interventions requires an understanding of the timescales of their effect. METHODS & FINDINGS: Using a mathematical model for malaria transmission which incorporates the acquisition and loss of both clinical and parasite immunity, we explore the impact of the trade-off between reduction in exposure and decreased development of immunity on the dynamics of disease following a transmission-reducing intervention such as insecticide-treated nets. Our model predicts that initially rapid reductions in clinical disease incidence will be observed as transmission is reduced in a highly immune population. However, these benefits in the first 5-10 years after the intervention may be offset by a greater burden of disease decades later as immunity at the population level is gradually lost. The negative impact of having fewer immune individuals in the population can be counterbalanced either by the implementation of highly-effective transmission-reducing interventions (such as the combined use of insecticide-treated nets and insecticide residual sprays) for an indefinite period or the concurrent use of a pre-erythrocytic stage vaccine or prophylactic therapy in children to protect those at risk from disease as immunity is lost in the population. CONCLUSIONS: Effective interventions will result in rapid decreases in clinical disease across all transmission settings while population-level immunity is maintained but may subsequently result in increases in clinical disease many years later as population-level immunity is lost. A dynamic, evolving intervention programme will therefore be necessary to secure substantial, stable reductions in malaria transmission

Object classification for robotic platforms

Computer vision has been revolutionised in recent years by increased research in convolutional neural networks (CNNs); however, many challenges remain to be addressed in order to ensure fast and accurate image processing when applying these techniques to robotics. These challenges consist of handling extreme changes in scale, illumination, noise, and viewing angles of a moving object. The project main contribution is to provide insight on how to properly train a convolutional neural network (CNN), a specific type of DNN, for object tracking in the context of industrial robotics. The proposed solution aims to use a combination of documented approaches to replicate a pick-and-place task with an industrial robot using computer vision feeding a YOLOv3 CNN. Experimental tests, designed to investigate the requirements of training the CNN in this context, were performed using a variety of objects that differed in shape and size in a controlled environment. The general focus was to detect the objects based on their shape; as a result, a suitable and secure grasp could be selected by the robot. The findings in this article reflect the challenges of training the CNN through brute force. It also highlights the different methods of annotating images and the ensuing results obtained after training the neural network

Porphyrin-Based Metal-Organic Frameworks as Heterogeneous Catalysts in Oxidation Reactions

Porphyrin-based Metal-Organic Frameworks (Por-MOFs) constitute a special branch of the wide MOF family that has proven its own value and high potential in different applications. In this mini-review the application of these materials as catalysts in oxidation reactions is highlighted

Timing of daily calorie loading affects appetite and hunger responses without changes in energy metabolism in healthy subjects with obesity

Acknowledgments The authors gratefully acknowledge Sylvia Stephen, Jean Bryce, Nina Lamza, Karen Taylor, Melanie Hudson, Kat Niblock, Ewa Wojtaczka, Aimee Sutherland, David Bremner, Claire Kidd, and Alicia Bryce at the Human Nutrition Unit of the Rowett Institute for their support in meal preparation and participant assessment. The authors acknowledge the contribution of NIHR Core Biochemistry Assay Laboratory, Cambridge Biomedical Research Centre (gut hormone analysis), and Loek Wouters at Maastricht University, Netherlands (DLW analysis). The authors also gratefully acknowledge Claus-Dieter Mayer for statistical analysis and modeling of the gastric emptying data. The authors gratefully acknowledge funding from the Medical Research Council (grant MR/P012205/1, The Big Breakfast study). A.M.J., P.J.M., G.W.H., and J.A.N.F. also acknowledge funding support from the Scottish Government, Rural and Environment Science and Analytical Services Division. Author contributions Conceptualization, design, and funding acquisition, A.M.J., P.J.M., and J.D.J.; investigation, L.C.R.-C. and C.L.F.; DLW analysis and modeling, K.R.W.; statistical analysis, G.W.H. and J.A.N.F.; writing – original draft, L.C.R.-C. and A.M.J.; writing – review & editing, all authors.Peer reviewedPublisher PD