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As antimicrobial susceptibility of common bacterial pathogens decreases, ensuring optimal dosing may preserve the use of older antibiotics in order to limit the spread of resistance to newer agents. Beta-lactams represent the most widely prescribed antibiotic class, yet most were licensed prior to legislation changes mandating their study in children. As a result, significant heterogeneity persists in the pediatric doses used globally, along with quality of evidence used to inform dosing. This review summarizes dosing recommendations from the major pediatric reference sources and tries to answer the questions: Does beta-lactam dose heterogeneity matter? Does it impact pharmacodynamic target attainment? For three important severe clinical infections—pneumonia, sepsis, and meningitis—pharmacokinetic models were identified for common for beta-lactam antibiotics. Real-world demographics were derived from three multicenter point prevalence surveys. Simulation results were compared with minimum inhibitory concentration distributions to inform appropriateness of recommended doses in targeted and empiric treatment. While cephalosporin dosing regimens are largely adequate for target attainment, they also pose the most risk of neurotoxicity. Our review highlights aminopenicillin, piperacillin, and meropenem doses as potentially requiring review/optimization in order to preserve the use of these agents in future.

The analysis of safety data from spontaneous reporting systems has a proven value for the detection and analysis of the risks of medicines following their placement on the market and use in medical practice. EudraVigilance is the pharmacovigilance database to manage the collection and analysis of suspected adverse reactions to medicines authorised in the European Economic Area. EudraVigilance first operated in December 2001, with access to the database being governed by the EudraVigilance access policy. We performed a literature search including data up to December 2016 to demonstrate how the data from EudraVigilance has been used in scientific publications. We describe the results, including by type of publication, research topics and drugs involved. In 50% of the publications, the data are used to describe safety issues, in 44% to analyse methodologies used in pharmacovigilance activities and in 6% to support clinical perspectives. We also outline a description of the use of the database by the European Union regulatory network. Driven by the full implementation of the 2010 pharmacovigilance legislation, EudraVigilance has undergone further enhancements together with a major revision of its access policy, taking into account the use of the new individual case safety report standard developed by the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use and the International Organization for Standardization. The aim of the broadened access is to facilitate more effective safety monitoring of authorised medicines, to make more data available for research and to provide better access to information on suspected adverse reactions for healthcare professionals and patients. In November 2017, the new full functionalities of EudraVigilance were launched, including the extensive web access to data on suspected adverse drug reactions and the possibilities for academic research institutions to request a more extensive dataset for the purposes of health research. The main objective of this article is to describe the new access to the database together with the opportunities that this new access can bring for research. It is intended to promote an appropriate use of the data to support the safe and effective use of medicines.

Clinical pharmacology is a medical specialty whose practitioners teach, undertake research, frame policy, give information and advice about the actions and proper uses of medicines in humans and implement that knowledge in clinical practice. It involves a combination of several activities: drug discovery and development, training safe prescribers, providing objective and evidence-based therapeutic information to ethics, regulatory and pricing bodies, supporting patient care in an increasingly subspecialized arena where co-morbidities, polypharmacy, altered pharmacokinetics and drug interactions are common and developing and contributing to medicines policies for Governments. Clinical pharmacologists must advocate drug quality and they must also advocate for sustainability of the Discipline. However for this they need appropriate clinical service and training support. This Commentary discusses strategies to ensure the Discipline is supported by teaching, training and policy organizations, to communicate the full benefits of clinical pharmacology services, put amonetary value on clinical pharmacology services and to grow the clinical pharmacology workforce to support a growing clinical, academic and regulatory need.

The authors of the above paper would like to make readers aware that two authors inadvertently failed to cite support from a key grant that supported a part of the research presented in this Review. Bruce Blumberg and Vesna Munic Kos would like to add the following funding source to their list of funders. The correct wording, as it should have appeared, is below: "This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement GOLIATH No. 825489." The authors apologise for this omission.

Background Clinical pharmacy practice in hospitals is a new role for pharmacists in Sudan. Pharmacists have to face the challenge of moving from their traditional roles within the pharmacy premises to new roles on the wards with direct contact with patients and other healthcare professionals. Objectives To explore the role and challenges facing the clinical pharmacists of Sudan. Settings Two of the main government hospitals in Sudan and an online survey. Method This study applied a two phase mixed method, a focus group discussion and a survey. A FGD was conducted with the clinical pharmacists in two of the main government hospitals in Sudan. This was followed by an on-line survey among the clinical pharmacists of Sudan. Main outcome measure The role of the clinical pharmacists of Sudan and the challenges facing clinical pharmacy practice. Results Four pharmacists participated in the focus group and 51 out of 140 pharmacists (34%) completed the on-line survey. The roles that were perceived by the majority of pharmacists as part of their duties in hospitals in Sudan were identifying drug-related problems (100%, n = 51), providing drug-related information to healthcare professionals by (96%, n = 47), and educating patients about their medicines (96%, n = 48). The pharmacists identified a number of obstacles that hindered their progress in practice. These obstacles were related to the pharmacists themselves, the lack of senior clinical pharmacists for leadership, the environment they were working in and the training they had received in clinical pharmacy. Conclusion The new clinical pharmacists in Sudan faced several challenges that need to be overcome in order to move forward in their clinical practice. To do so they will require support from pharmacy educational institutions, other healthcare professionals and the healthcare institutions they are working within.

Aquaglyceroporin-2 is a known determinant of melarsoprol-pentamidine cross-resistance in Trypanosoma brucei brucei laboratory strains. Recently, chimerization at the AQP2-AQP3 tandem locus was described from melarsoprol-pentamidine cross-resistant Trypanosoma brucei gambiense isolates from sleeping sickness patients in the Democratic Republic of the Congo. Here, we demonstrate that reintroduction of wild-type AQP2 into one of these isolates fully restores drug susceptibility while expression of the chimeric AQP2/3 gene in aqp2-aqp3 null T. b. brucei does not. This proves that AQP2-AQP3 chimerization is the cause of melarsoprol-pentamidine cross-resistance in the T. b. gambiense isolates.

Positive ignorance is the putting in to question of, and sometimes moving on from, the knowledge we think we have, and asking where it might be just or helpful to do so. Drawing primarily on the work of Barbara Johnson, this article shows how the notion of positive ignorance might be offered as a tool in the context of education and educational research. Partly a critical development of Richard Smith's argument in 'The Virtues of Unknowing', I attempt to understand 'unknowing' as an active rather than passive form of 'not knowing', in a manner that challenges some aspects of 'the virtues of unknowing' and its concomitant epistemological and ethical positions, not least those tied to Smith's advocacy for what he calls the 'well-stocked mind'. Unknowing, in my reading, is not a dispositional acceptance of the desirability of nonknowledge, instead, unknowing is a means of epistemological resistance, especially against that which, often with very real social and political consequences, is presented as self-evident.

I explore theoretical conceptions of the use and exchange values of mathematics education within cultural-historical activity theory perspectives. The case of education in England is compared with that of health care (due to Engestrom). Then I draw on Lave and McDermott's study of estranged learning from the early Marx, and from Marx's later analyses in Capital. They deduced the source of learners' alienation from learning in the enforced conditions of education, run by the educational establishment. However, I find their analogy limiting and hence erroneous. I turn to Capital to find the Marxian analysis of the peculiar commodity: Enhanced labor power. I conclude that the use-value of mathematics education derives from (a) learners' immediate consumption, and (b) their enhanced (mental) labor power. Although this explains the root, economic contradictions, cultural systems of exchange explain how these are symbolised in cultural forms of use and exchange value. Copyright © Regents of the University of California.

Four regioisomeric azulenes bearing pentafluorosulfanylphenyl substituents have been prepared and characterised by various spectroscopic techniques. The absorption spectra are qualitatively similar in the visible region for all isomers, but upon protonation exhibit pronounced variation dependent on the connectivity within each molecule. This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 665992

Two-photon fluorescence microscopy has become an indispensable technique for cellular imaging. Whereas most two-photon fluorescent probes rely on well-known fluorophores, here we report a new fluorophore for bioimaging, namely azulene. A chemodosimeter, comprising a boronate ester receptor motif conjugated to an appropriately substituted azulene, is shown to be an effective two-photon fluorescent probe for reactive oxygen species, showing good cell penetration, high selectivity for peroxynitrite, no cytotoxicity, and excellent photostability. This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 665992

The aim of this article is to examine how women with children define 'moral' behaviour in relation to the issue of divorce. The data consist of life stories written by married Finnish mothers who say that they have contemplated divorce or separation. The analytical focus is on how the decision process is narratively constructed. The theories around a feminist ethic of care provide the theoretical framework for the discussion, and I examine how concrete individuals in specific situations negotiate morality. The narrators present their decision to divorce or stay married as a moral dilemma and argue for their own solutions in moral terms. I also consider the consequences of using an ethic of care in the study of divorce. © 2005 Elsevier Ltd. All rights reserved.

The Soviet Union under Stalin is not often thought of as an environment conducive to inter-personal trust. The article builds on recent research which suggests that trust may exist in contexts marked by high levels of coercion, to look for signs of trust at the apex of the Stalinist political system. It identifies two sources of trust, one consisting of incipient institutions whose rules were only ambiguously defined, and the other of komprotnat whose practice in certain areas was sufficiently systematic to support trust on certain issues. The article concludes by arguing that although the practice of komprotnat persisted, the social values supporting it changed with Stalin's death.

We investigated whether imagining contact with an outgroup member would change intergroup behaviour. Participants who had imagined a positive interaction with an outgroup member or an unspecified stranger were told that they were about to take part in a discussion task with an outgroup member. They were taken to a room and asked to set out two chairs ready for the discussion while the experimenter left, ostensibly to find the other participant. The distance between the two chairs was then measured. Undergraduate students who imagined talking to an obese individual (Experiment 1) or a Muslim individual (Experiment 2) placed the chairs significantly closer than those in the control condition. They also reported more positive feelings and beliefs regarding Muslims. These findings highlight an important practical application of imagined contact: preparing people for successful face-to-face contact.

This article pursues the goal of going beyond Saidian notions of Orientalism and Said's assumption of the "complicity of knowledge with power" to reach back to Foucault's initial postulations on the role of institutions and the intellectual in the interplay of power/knowledge relations. The article concentrates on the role of Russian military Oriental studies institutions and Orientologists in the context of discourses (the promotion of Russkoe Delo, the juxtaposition of Russia with the West and the Orient, etc.) that existed in late Imperial Russia and influenced the accumulation and development of scholarly knowledge on the Orient. Therefore, the significant contribution of the military domain to Russian Oriental studies on both the institutional and individual levels are examined from the angle of intra-Russian discourses in the period from the establishment of the Asiatic Section of the General Staff in 1863 up to 1917. © 2013 The International Society for Iranian Studies.

In the present, we like to conceive of peace as the absence of its perceived opposite: we imagine it to be the normal, permanent state of society, which is only occasionally (and hopefully extremely rarely) interrupted by an abnormal, different state, that of war. Peace, in this context, we imagine as the near-complete absence of violent conflicts. War, on the other hand, we see as characterised by a significantly increased occurrence or even dominance of violent means of resolving conflicts. This conception, we also like to transfer onto the (close and more distant) past, in which we seem to mostly be interested in war (which sometimes is even referred to as the 'father of all things'). The reason for this, particularly in prehistory, seems to be that war seems to have left more archaeologically identifiable material traces than peace. Starting with weapons and other instruments of warfare via direct traces – whether anthropologically identifiable as trauma on skeletal remains, or archaeologically by stray finds of weapons on 'battlefields' – to defensive and offensive architecture; war seems to be relatively easily traceable by archaeological means. Peace, on the other hand, seems only identifiable negatively, through the absence of evidence for war. As understandable as this conception may be, so misleading it is: peace is not a natural state, occurring automatically if nobody goes to war. Rather, much like war, it requires social organisation and also enforcement, often with violent means. An executioner's sword is not a weapon of war, nor the head severed by it an injury of war, but rather a trace of the violent enforcement or re-establishment of peace. It is thus argued in this contribution that much of what we, as yet, have understood to be the 'archaeology of warfare' might as well be an 'archaeology of peace', since war and peace can hardly be distinguished from each other by archaeological means.