Statistical analysis plan for the randomized controlled trial Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)

Background: Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up lschaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings. Objective: To publish the detailed statistical analysis plan for TWIST prior to unblinding. Methods: The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CON-SORT) statement and provides clear and open reporting. Discussion: Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses.Peer reviewe

Statistical analysis plan for the randomized controlled trial Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)

Background: Patients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up lschaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings. Objective: To publish the detailed statistical analysis plan for TWIST prior to unblinding. Methods: The TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CON-SORT) statement and provides clear and open reporting. Discussion: Publication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses.Peer reviewe

The ME Bandwagon and other labels: Constructing the authentic case in talk about a controversial illness

This paper examines the discourse of morality surrounding ‘ME’ as a contested illness, looking at how GPs and ME group members differentiate between the category of ‘genuine ME sufferer’ and the ‘bandwagon’. ‘Jumping on the bandwagon’ is a metaphor commonly used to describe the activity of ‘following the crowd’ in order to gain an advantage. This discursive analysis shows how ‘bandwagon’ categories are constructed in contrast to the category of genuine sufferer. People who jump on the bandwagon are accused of matching their symptoms to media stereotypes, adopting trendy illnesses (‘fads’,) or using ‘tickets’ to avoid facing up to psychological illnesses. Both GPs and ME group members construct a differential moral ordering of physical and psychological illness categories, where the latter assumes a lesser status. The paper concludes that against a background of medical uncertainty and controversy, the ‘bandwagon’ and other derogatory labels function as contrast categories that work to establish the existence of ‘ME’ as a genuine illness

A new human challenge model for testing heat-stable toxin-based vaccine candidates for enterotoxigenic Escherichia coli diarrhea - dose optimization, clinical outcomes, and CD4+T cell responses

Enterotoxigenic Escherichia coli (ETEC) are a common cause of diarrheal illness in young children and travelers. There is yet no licensed broadly protective vaccine against ETEC. One promising vaccine development strategy is to target strains expressing the heat-stable toxin (ST), particularly the human ST (STh), since infections with these strains are among the leading causes of diarrhea in children in low-and-middle income countries. A human challenge model based on an STh-only ETEC strain will be useful to evaluate the protective efficacy of new ST-based vaccine candidates. To develop this model, we experimentally infected 21 healthy adult volunteers with the epidemiologically relevant STh-only ETEC strain TW10722, identified a suitable dose, assessed safety, and characterized clinical outcomes and immune responses caused by the infection. Doses of 1x10(10) colony-forming units (CFU) of TW10722 gave a suitable attack risk of 67% for moderate or severe diarrhea and an overall diarrhea attack risk of 78%. Non-diarrheal symptoms were mostly mild or moderate, and there were no serious adverse events. During the first month after ingesting the challenge strain, we measured significant increases in both activated CD4+ T cells and levels of serum IgG and IgA antibodies targeting coli surface antigen 5 (CS5) and 6 (CS6), as well as the E. coli mucinase YghJ. The CS5-specific CD4+ T cell and antibody responses were still significantly elevated one year after experimental infection. In conclusion, we have developed a safe STh-only ETEC-based human challenge model which can be efficiently used in Phase 2B trials to evaluate the protective efficacy of new ST-based vaccine candidates

“Es fundamental que la información que se transmita sea confiable”

El flamante Doctor Honoris Causa de la UNLP, Emilio Luque Fadón, de la Universidad Autónoma de Barcelona, fue uno de los conferencistas de CACIC 2017. Durante su estadía por la ciudad de La Plata, el español habló acerca de las nuevas tecnologías, su tolerancia a los fallos y el consumo energético.Facultad de Informátic

Abusing Foucault: Methodology, critique and subversion

This paper examines the uses to which Foucault's work has been put in a variety of areas in the social sciences. The argument is made that Foucault's work is often used to legitimate practices which bear little resemblence to the original and are frequently based on a misunderstanding of his method. Foucault's work should not be turned into a slogan and then inserted within an existing political project. Foucault's work invites scepticism rather than dogmatic belief. The argument is illustrated with examples

After Lashley: neuropsychology, metaphors, promissory notes.

The argument is that the rhetoric of psychology needs to be analysed in order to understand the processes of persuasion within the discipline. The work of the neurologist Karl Lashley is used to examine the ways in which a particular problem, the localization of memory, was characterized around 1950. An account is given of the holographic metaphor which was regarded as the solution to such a problem. It is suggested that such a metaphor could be regarded as a promissory note which was unfulfilled and rejected around 1980. A discussion is then given of the ways in which Lashley's work is currently being characterized. It is suggested that the assumption of modularity, or the `boxes in the brain' metaphor, could be regarded as another promissory note, and a number of the incentives offered for the acceptance of such a promise are reviewed