Protocol for Deferral of Consent in Acute Stroke Trials.

The challenges of conducting hyperacute stroke research and obtaining informed consent have been increasingly recognized within the stroke research community in recent years. Deferral of consent, in which a patient is enrolled in a trial and then provides consent at some point thereafter, is increasingly used to enroll patients into hyperacute stroke trials in Canada and Europe, although it is not permitted in the United States. Deferral of consent offers several potential advantages-quicker door-to-randomization, increased enrolment, decreased selection bias-but these must be balanced against the risk of enrolling patients against their wishes.

Pivotal roles for membrane phospholipids in axonal degeneration.

Membrane phospholipids are critical components of several signaling pathways. Maintained in a variety of asymmetric distributions, their trafficking across the membrane can be induced by intra-, extra-, and intercellular events. A familiar example is the externalization of phosphatidylserine from the inner leaflet to the outer leaflet in apoptosis, inducing phagocytosis of the soma.

Ethical Justification for Deferral of Consent in the AcT Trial for Acute Ischemic Stroke.

The AcT trial (Alteplase Compared to Tenecteplase) compares alteplase or tenecteplase for patients with acute ischemic stroke. All eligible patients are enrolled by deferral of consent. Although the use of deferral of consent in the AcT trial meets the requirements of Canadian policy, we sought to provide a more explicit and rigorous approach to the justification of deferral of consent organized around 3 questions.

Goods, causes and intentions: problems with applying the doctrine of double effect to palliative sedation.

Background: Palliative sedation and analgesia are employed in patients with refractory and intractable symptoms at the end of life to reduce their suffering by lowering their level of consciousness. The doctrine of double effect, a philosophical principle that justifies doing a "good action" with a potentially "bad effect," is frequently employed to provide an ethical justification for this practice.

Main Text: We argue that palliative sedation and analgesia do not fulfill the conditions required to apply the doctrine of double effect, and therefore its use in this domain is inappropriate.

Axonal degeneration induces distinct patterns of phosphatidylserine and phosphatidylethanolamine externalization.

Axonal degeneration is a common feature of multiple neurodegenerative diseases, yet the mechanisms underlying its various manifestations are incompletely understood. We previously demonstrated that axonal degeneration is associated with externalization of phosphatidylserine (PS), which precedes morphological evidence of degeneration, is redox-sensitive, and is delayed in Wallerian degeneration slow (Wld) mutant animals. Phosphatidylethanolamine (PE) is the other major membrane phospholipid in the inner leaflet of the cell membrane, and given that PS signals apoptosis, phagocytosis, and degeneration, we hypothesized that PS and PE membrane dynamics play distinct roles in axonal degeneration.