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Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating form of stroke frequently affecting young to middle-aged adults, with an unmet need to improve outcome. This special report focusses on the development of intrathecal haptoglobin supplementation as a treatment by reviewing current knowledge and progress, arriving at a Delphi-based global consensus regarding the pathophysiological role of extracellular hemoglobin and research priorities for clinical translation of hemoglobin-scavenging therapeutics. After aneurysmal subarachnoid hemorrhage, erythrocyte lysis generates cell-free hemoglobin in the cerebrospinal fluid, which is a strong determinant of secondary brain injury and long-term clinical outcome. Haptoglobin is the body’s first-line defense against cell-free hemoglobin by binding it irreversibly, preventing translocation of hemoglobin into the brain parenchyma and nitric oxide-sensitive functional compartments of cerebral arteries. In mouse and sheep models, intraventricular administration of haptoglobin reversed hemoglobin-induced clinical, histological, and biochemical features of human aneurysmal subarachnoid hemorrhage. Clinical translation of this strategy imposes unique challenges set by the novel mode of action and the anticipated need for intrathecal drug administration, necessitating early input from stakeholders. Practising clinicians (n=72) and scientific experts (n=28) from 5 continents participated in the Delphi study. Inflammation, microvascular spasm, initial intracranial pressure increase, and disruption of nitric oxide signaling were deemed the most important pathophysiological pathways determining outcome. Cell-free hemoglobin was thought to play an important role mostly in pathways related to iron toxicity, oxidative stress, nitric oxide, and inflammation. While useful, there was consensus that further preclinical work was not a priority, with most believing the field was ready for an early phase trial. The highest research priorities were related to confirming haptoglobin’s anticipated safety, individualized versus standard dosing, timing of treatment, pharmacokinetics, pharmacodynamics, and outcome measure selection. These results highlight the need for early phase trials of intracranial haptoglobin for aneurysmal subarachnoid hemorrhage, and the value of early input from clinical disciplines on a global scale during the early stages of clinical translation.

In most Latin American nations there is a semblance of a free press. But here one simply wouldn't think of making the rounds of offices and contacts hoping for tips, background and exclusives. At the time of the French Revolution Haiti also blew up, first in slave insurrection and later in civil war. Withal, it is a land of mountainous beauty arid of a warm, handsome, exceptionally artistic people, a great number of them descendants of the Ibo slaves from West Africa. Haiti is the poorest of Latin American nations and, in the conduct of those who govern, possibly the most violent. Death for interfering with the government is a common and casual reward. Death from misery is as Haitian as voodoo.

The binding of insulin to its receptor in rat adipocyte and isolated plasma membranes has been measured. The adipocyte insulin receptor has been reconstituted in lecithin liposomes and the binding of insulin investigated. A method of interpreting binding data presented as binding vs. the logarithm of free insulin concentration (binding isotherms) in terms of the binding potential concept of Wyman (1965) is described, and the results are compared with the commonly used Scatchard analysis of binding. The binding potential approach enables binding constants and Gibbs energies of formation of the insulin-receptor complex to be determined as a function of insulin bound. The limiting Gibbs energies of binding at 15°C to intact cells, membranes and liposomes were found to be -55, -52 and -49 kJ mol-1 respectively. The affinity of the receptor for insulin decreases smoothly with increase in binding in all three systems. For intact adipocytes the number of insulin receptors per cell is found to be approximately 43,000.

The article discusses the disparaging comments about the leadership of the Australian Computer Society (ACS). ACS has made substantial progress in policy development, industry liaison and government lobbying, all of which have enhanced ability to positively influence decisions affecting industry and profession. Corporations in Australia are spending small fortunes each year in an attempt to firewall their systems against attack, not only from outsiders but from malicious and naive sources within. Australia Computer Online probably got more exposure than it bargained for when its artwork from July 2001 was inadvertently published in APC.

Submissions by football, basketball, volleyball, baseball, soccer, and softball officials describing their best call or decision on the field are presented.

Several letters to the editor are presented in response to articles in previous issues, including one on why rugby sevens is refused entry into the Olympics by the International Olympic Committee and another on the need for a semi-professional rugby team in the Welsh Premiership to develop young rugby players.