Eculizumab in paraxysmal nocturnal haemogloburinia and atypical haemolytic syndrome 10-year pharmacovigilance analysis

Eculizumab is the first and only medication approved for paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS) treatment. However, eculizumab safety based on long‐term pharmacovigilance is unknown. This analysis summarises safety data collected from spontaneous and solicited sources from 16 March 2007 through 1 October 2016. Cumulative exposure to eculizumab was 28 518 patient‐years (PY) (PNH, 21 016 PY; aHUS, 7502 PY). Seventy‐six cases of meningococcal infection were reported (0·25/100 PY), including eight fatal PNH cases (0·03/100 PY). Susceptibility to meningococcal infections remained the key risk in patients receiving eculizumab. The meningococcal infection rate decreased over time; related mortality remained steady. The most commonly reported serious nonmeningococcal infections were pneumonia (11·8%); bacteraemia, sepsis and septic shock (11·1%); urinary tract infection (4·1%); staphylococcal infection (2·6%); and viral infection (2·5%). There were 434 reported cases of eculizumab exposure in pregnant women; of 260 cases with known outcomes, 70% resulted in live births. Reporting rates for solid tumours (≈0·6/100 PY) and haematological malignancies (≈0·74/100 PY) remained stable over time. No new safety signals affecting the eculizumab benefit‐risk profile were identified. Continued awareness and implementation of risk mitigation protocols are essential to minimise risk of meningococcal and other Neisseria infections in patients receiving eculizumab

A validation of Amazon Mechanical Turk for the collection of acceptability judgments in linguistic theory

Amazon’s Mechanical Turk (AMT) is a Web application that provides instant access to thousands of potential participants for survey-based psychology experiments, such as the acceptability judgment task used extensively in syntactic theory. Because AMT is a Web-based system, syntacticians may worry that the move out of the experimenter-controlled environment of the laboratory and onto the user-controlled environment of AMT could adversely affect the quality of the judgment data collected. This article reports a quantitative comparison of two identical acceptability judgment experiments, each with 176 participants (352 total): one conducted in the laboratory, and one conducted on AMT. Crucial indicators of data quality—such as participant rejection rates, statistical power, and the shape of the distributions of the judgments for each sentence type—are compared between the two samples. The results suggest that aside from slightly higher participant rejection rates, AMT data are almost indistinguishable from laboratory data

The forms of repetition in social and environmental reports: insights from Hume's notion of ?impressions?

This paper focuses on the use of repetition, both in narrative and visual forms, in social and environmental reports. It investigates the forms of repetition as a rhetorical device adopted by the preparer of a social and environmental report in helping the process of knowledge acquisition, as outlined by Hume (1739). Drawing from Hume?s (1739) philosophical idea of an ?impression?, and the work of Davison (2014a) we classify repetitions into ?identical?, ?similar? and ?accumulated? forms. It is argued that the rationale for distinguishing between the different forms of repetition can be linked to their different potential or intensity in acting on different stimuli with a view to enhance learning. The empirical element of this study is based on the stand-alone social and environmental reports of a sample of 86 cooperative banks in Northern Italy; the analysis of these reports indicates that repetition is widespread and that cooperative banks use all forms of repetition, albeit to a varying extent within the different reported themes. The paper contributes to the literature by offering an alternative interpretation of repetition using an interdisciplinary perspective and by providing new insights on social and environmental reporting practices in the cooperative banking sector

Minimalist C/case

This article discusses A-licensing and case from a minimalist perspective, pursuing the idea that argument NPs cyclically enter a number of A-relations, rather than just a single one, resulting in event-licensing, case-licensing and phi-licensing. While argument case commonly reflects Voice/v-relations, canonical A-movement is driven by higher elements, either in the C-T system or in a superordinate v-system (in ECM constructions). In addition, there is a distinction to be drawn between the triggering of A-movement, by for example C, and the licensing of the landing site, by for instance T, C-probing leading to tucking-in into Spec-T. Much of the evidence presented comes from quirky case constructions in Icelandic and from ECM and raising constructions in Icelandic and English. It is argued that T in ECM constructions inherits phi-licensing from the matrix v, regardless of the case properties of v

Impact of Diabetes on Postinfarction Heart Failure and Left Ventricular Remodeling

Diabetes mellitus, the metabolic syndrome, and the underlying insulin resistance are increasingly associated with diastolic dysfunction and reduced stress tolerance. The poor prognosis associated with heart failure in patients with diabetes after myocardial infarction is likely attributable to many factors, important among which is the metabolic impact from insulin resistance and hyperglycemia on the regulation of microvascular perfusion and energy generation in the cardiac myocyte. This review summarizes epidemiologic, pathophysiologic, diagnostic, and therapeutic data related to diabetes and heart failure in acute myocardial infarction and discusses novel perceptions and strategies that hold promise for the future and deserve further investigation