The Evolution of Flow Chemistry: An Opinion on Factors Driving Innovation

This article seeks to provide an overview of the environmental factors within the pharmaceutical industry that have contributed to the emergence of flow chemistry over the past two decades. It highlights some of the challenges facing the industry and describes how they are being overcome by the exponential trajectory of scientific progress in the area. We identify current trends and offer a speculative glimpse into the future of drug development and manufacturing with some examples of progress being made at CARBOGEN AMCIS

Cellular actors, Toll-like receptors, and local cytokine profile in acute coronary syndromes

Aims Inflammation plays a key role in acute coronary syndromes (ACS). Toll-like receptors (TLR) on leucocytes mediate inflammation and immune responses. We characterized leucocytes and TLR expression within coronary thrombi and compared cytokine levels from the site of coronary occlusion with aortic blood (AB) in ACS patients. Methods and results In 18 ACS patients, thrombi were collected by aspiration during primary percutaneous coronary intervention. Thrombi and AB from these patients as well as AB from 10 age-matched controls without coronary artery disease were assessed by FACS analysis for cellular distribution and TLR expression. For further discrimination of ACS specificity, seven non-coronary intravascular thrombi and eight thrombi generated in vitro were analysed. In 17 additional patients, cytokine levels were determined in blood samples from the site of coronary occlusion under distal occlusion and compared with AB. In coronary thrombi from ACS, the percentage of monocytes related to the total leucocyte count was greater than in AB (47 vs. 20%, P = 0.0002). In thrombi, TLR-4 and TLR-2 were overexpressed on CD14-labelled monocytes, and TLR-2 was increased on CD66b-labelled granulocytes, in comparison with leucocytes in AB. In contrast, in vitro and non-coronary thrombi exhibited no overexpression of TLR-4. Local blood samples taken under distal occlusion revealed elevated concentrations of chemokines (IL-8, MCP-1, eotaxin, MIP-1α, and IP-10) and cytokines (IL-1ra, IL-6, IL-7, IL-12, IL-17, IFN-α, and granulocyte-macrophage colony-stimulating factor) regulating both innate and adaptive immunity (all P < 0.05). Conclusion In ACS patients, monocytes accumulate within thrombi and specifically overexpress TLR-4. Together with the local expression patterns of chemokines and cytokines, the increase of TLR-4 reflects a concerted activation of this inflammatory pathway at the site of coronary occlusion in AC

ESVM guidelines:the diagnosis and management of Raynaud's phenomenon

Regarding the clinical diagnosis of Raynaud's phenomenon and its associated conditions, investigations and treatment are substantial, and yet no international consensus has been published regarding the medical management of patients presenting with this condition. Most knowledge on this topic derives from epidemiological surveys and observational studies; few randomized studies are available, almost all relating to drug treatment, and thus these guidelines were developed as an expert consensus document to aid in the diagnosis and management of Raynaud's phenomenon. This consensus document starts with a clarification about the definition and terminology of Raynaud's phenomenon and covers the differential and aetiological diagnoses as well as the symptomatic treatment

ECLAIRE: Effects of Climate Change on Air Pollution Impacts and Response Strategies for European Ecosystems. Project final report

The central goal of ECLAIRE is to assess how climate change will alter the extent to which air pollutants threaten terrestrial ecosystems. Particular attention has been given to nitrogen compounds, especially nitrogen oxides (NOx) and ammonia (NH3), as well as Biogenic Volatile Organic Compounds (BVOCs) in relation to tropospheric ozone (O3) formation, including their interactions with aerosol components. ECLAIRE has combined a broad program of field and laboratory experimentation and modelling of pollution fluxes and ecosystem impacts, advancing both mechanistic understanding and providing support to European policy makers. The central finding of ECLAIRE is that future climate change is expected to worsen the threat of air pollutants on Europe’s ecosystems. Firstly, climate warming is expected to increase the emissions of many trace gases, such as agricultural NH3, the soil component of NOx emissions and key BVOCs. Experimental data and numerical models show how these effects will tend to increase atmospheric N deposition in future. By contrast, the net effect on tropospheric O3 is less clear. This is because parallel increases in atmospheric CO2 concentrations will offset the temperature-driven increase for some BVOCs, such as isoprene. By contrast, there is currently insufficient evidence to be confident that CO2 will offset anticipated climate increases in monoterpene emissions. Secondly, climate warming is found to be likely to increase the vulnerability of ecosystems towards air pollutant exposure or atmospheric deposition. Such effects may occur as a consequence of combined perturbation, as well as through specific interactions, such as between drought, O3, N and aerosol exposure. These combined effects of climate change are expected to offset part of the benefit of current emissions control policies. Unless decisive mitigation actions are taken, it is anticipated that ongoing climate warming will increase agricultural and other biogenic emissions, posing a challenge for national emissions ceilings and air quality objectives related to nitrogen and ozone pollution. The O3 effects will be further worsened if progress is not made to curb increases in methane (CH4) emissions in the northern hemisphere. Other key findings of ECLAIRE are that: 1) N deposition and O3 have adverse synergistic effects. Exposure to ambient O3 concentrations was shown to reduce the Nitrogen Use Efficiency of plants, both decreasing agricultural production and posing an increased risk of other forms of nitrogen pollution, such as nitrate leaching (NO3-) and the greenhouse gas nitrous oxide (N2O); 2) within-canopy dynamics for volatile aerosol can increase dry deposition and shorten atmospheric lifetimes; 3) ambient aerosol levels reduce the ability of plants to conserve water under drought conditions; 4) low-resolution mapping studies tend to underestimate the extent of local critical loads exceedance; 5) new dose-response functions can be used to improve the assessment of costs, including estimation of the value of damage due to air pollution effects on ecosystems, 6) scenarios can be constructed that combine technical mitigation measures with dietary change options (reducing livestock products in food down to recommended levels for health criteria), with the balance between the two strategies being a matter for future societal discussion. ECLAIRE has supported the revision process for the National Emissions Ceilings Directive and will continue to deliver scientific underpinning into the future for the UNECE Convention on Long-range Transboundary Air Pollution

ECLAIRE third periodic report

The ÉCLAIRE project (Effects of Climate Change on Air Pollution Impacts and Response Strategies for European Ecosystems) is a four year (2011-2015) project funded by the EU's Seventh Framework Programme for Research and Technological Development (FP7)