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This report supports the European Commission’s revision of the EEAG and section 7 of the GBER. It consists of 3 study items that address distinct questions: Study Item 1: The measurement of cost-effectiveness (EUR per tonne of CO2 avoided) allows for the assessment of relative decarbonisation benefits of policies, but may not always capture their overall environmental impact. Wind, solar and energy efficiency have similar cost-effectiveness, while cogeneration of heat and power is less cost-effective. Fo cusing on decarbonisation objectives only, multi-technology auctions improve cost-effec tiveness by prioritising less costly technologies. If potential inframarginal rents and dy namic effects are also considered, then technology-specific auctions may exhibit lower carbon mitigation costs in some cases. Study Item 2: Research on operating and investment aid is reviewed, with the finding that for environmentally friendly energy aid, some distortions have arisen from the nature of aid, but that both investment and especially operating aid can yield positive outcomes. Analysis of four actual schemes with operating or investment aid suggests that precise scheme design matters for success and often evolves with time. Three aid schemes are examined for industrial decarbonisation. Aid levels of 40% for fixed aid intensity are deemed unlikely, if the maximum aid intensities remain unchanged, to provide sufficient support for several industrial decarbonisation routes. Study Item 3: Empirical studies support the relevance of electro-intensity and trade in tensity for eligibility of energy-intensive users for levy exemptions in the EEAG. The anal ysis of levies from 2011 to 2018 highlights their large heterogeneity across sectors, coun tries and over time. Scenarios harmonising levies to the highest levy and abolishing ex emptions lead to a substantial decrease in profits. A limited profit decrease is predicted when levies change by a percentage value, an absolute level or are partially harmonised to a threshold. ispartof: Catalogue number: KD-05-21-173-EN-N pages:1-308 nrpages: 308 status: published

peer-reviewed Introduction: Ireland currently has the highest reported rate in Europe of vancomycin-resistant Enterococcus (VRE) isolated from the bloodstream, but data regarding the prevalence of VRE endocarditis remain scarce. Treatment options for Enterococcus-mediated endocarditis are limited, and therefore daptomycin is commonly used off licence in this setting. Case presentation: A 60-year-old male with end-stage kidney disease (ESKD) presented with VRE bacteraemia secondary to a gangrenous right foot colonized with vancomycin-resistant Enterococcus faecium. Aortic valve endocarditis was confirmed using transoesophageal echocardiography. Treatment was commenced with linezolid and subsequently modified to combination therapy with daptomycin and rifampicin. High-dose daptomycin therapy was employed unsuccessfully and, after 20 days of therapy, daptomycin resistance emerged, which proved fatal. Conclusion: The case was ethically challenging and involved a refusal of amputation and, ultimately, any form of treatment by the patient. In summary, however, daptomycin-resistant VRE bacteraemia complicated by recalcitrant daptomycin-resistant VRE endocarditis proved fatal for this patient. Further evaluation of the efficacy and safety of high-dose daptomycin for the treatment of VRE infective endocarditis is needed.

peer-reviewed In the context of the excellent report of successful control of an outbreak of carbapenemase-producing Klebsiella pneumoniae in an Italian neonatal intensive care unit published in this journal (1), we wish to report the consequences of the first outbreak of KPC-producing Kliebsiella in Ireland and how, despite identification of operational factors associated with the incidence and best efforts towards rectifying those, our 410-bed hospital in the West of Ireland is failing to control endemic KPCs. Globally, there is recognition of the significant morbidity and mortality implications associated with emergence of carbapenemase-producing bacteria (2). The resulting vigilance has resulted in enhanced reporting of outbreaks, many being the first of their kind in specific countries (3), and descriptions of molecular studies to determine incidence and transfer of the carbapenemase-encoding blaKPC-harboring IncFIA plasmid between clonal variants (4). With indicative rates of carriage being circa 20%, infection control specialists are reacting with novel techniques for microbiological detection, strategies for prevention of nosocomial transmission, and clinical microbiologists are facing therapeutic challenges related to limited, relatively unproven antimicrobial treatment options. ACCEPTED peer-reviewed

The purpose of this study was to examine a technique of Pre- Testing Advertisements for Effectiveness, and to seek to provide a Psychological basis for such Pre-Testing. The results of this study suggest a possible system for Pre-Testing the effectiveness of advertisements. The approach taken in this study was to test the effectiveness of communication of advertisements. Three advertisements were tested on a sample of a target audience, that Bample consisting of 78 people taken from three market segments; census classifications A, B, and Cl, whose ages ranged from 25 to 60. Respondents were given three tests : 1) Catalogue selection; 2) Focus of attention using an eye movement recorder test and; 3) completion of a questionnaire. Results showed significant differences between the effectiveness of the three experimental advertisements. Advertisements 1 and 2 failed to communicate the intended messages and were thus classified as ineffective. The 3rd advertisement was communicated effectively.Hence the system used, was shown to distinguish between advertisements. It is the aim of this study to establish whether the consumer decoded advertising communication in the manner intended by the sender, and to provide a scientifically based advertising/communication Pre-Test system which could prove useful for Advertising, Research, and for Psychology.

Astrocytes and microglia are emerging key regulators of activity-dependent synapse remodeling that engulf and remove synapses in response to changes in neural activity. Yet, the degree to which these cells communicate to coordinate this process remains an open question. Here, we use whisker removal in postnatal mice to induce activity-dependent synapse removal in the barrel cortex. We show that astrocytes do not engulf synapses in this paradigm. Instead, astrocytes reduce their contact with synapses prior to microglia-mediated synapse engulfment. We further show that reduced astrocyte-contact with synapses is dependent on microglial CX3CL1-CX3CR1 signaling and release of Wnts from microglia following whisker removal. These results demonstrate an activity-dependent mechanism by which microglia instruct astrocyte-synapse interactions, which then provides a permissive environment for microglia to remove synapses. We further show that this mechanism is critical to remodel synapses in a changing sensory environment and this signaling is upregulated in several disease contexts., Competing Interests: Declaration of interests Authors declare no competing interests.

Cre/LoxP technology has revolutionized genetic studies and allowed for spatial and temporal control of gene expression in specific cell types. The field of microglial biology has particularly benefited from this technology as microglia have historically been difficult to transduce with virus or electroporation methods for gene delivery. Here, we interrogate four of the most widely available microglial inducible Cre lines. We demonstrate varying degrees of recombination efficiency and spontaneous recombination, depending on the Cre line and loxP distance. We also establish best practice guidelines and protocols to measure recombination efficiency in microglia, which could be extended to other cell types. There is increasing evidence that microglia are key regulators of neural circuit structure and function. Microglia are also major drivers of a broad range of neurological diseases. Thus, reliable manipulation of their function in vivo is of utmost importance. Identifying caveats and benefits of all tools and implementing the most rigorous protocols are crucial to the growth of the field of microglial biology and the development of microglia-based therapeutics.