Macrocycles are Great Cycles. This was the title of a review we wrote in 2011 to reflect the increasing attention being then given by medicinal chemists toward this unique compound class. Six years later, the interest has only grown, which strongly indicates that the macrocycle field is not just another trend that becomes hot, generates frenetic activity, then rapidly vanishes or dissipates into irrelevance—quite the contrary. Macrocycles of very diverse chemical classes continue to generate a high level of interest from the drug discovery community, with an impressive number already in or entering the clinic. When we started working over 15 years ago at one of the pioneering companies in this area, NéoKimia (later Tranzyme Pharma), formed to realize the vision of Prof. Pierre Deslongchamps regarding libraries of conformationally defined and chemically diverse macrocyclic molecules, there was only one other company (Polyphor)primarily focused on using macrocycles for drug discovery purposes, and few academics had research focused on these structures. At the time, we met with considerable skepticism that such molecules could ever be effective synthetic drugs. Now, that situation has changed dramatically, with over 30 companies involved in pursuing macrocycles as a key aspect of their R&D, while the number of scientific papers on the topic has exploded .As a result, we felt it would be very timely to assemble a reference book on the medicinal chemistry of macrocycles. From the onset, we wanted this to be a practical guide targeting both experts and their teams, as well asneophytes.

Transfusion‐associated septic events have been reduced by the introduction of improved donor screening and skin disinfection methods, as well as implementation of first aliquot diversion and bacterial testing. Recent reports of septic reactions indicate that bacterial contamination of blood components continues to be the predominant transfusion‐associated infectious risk in Europe and North America . From 2011 to 2015, the US Food and Drug Administration (FDA) reported 14 fatalities caused by blood components contaminated with bacteria . In Canada, the Transfusion Transmitted Injuries Surveillance System Programme Report for 2006–12 described 33 transfusion reactions involving bacterially contaminated blood components . Only one probable transfusion reaction involving a platelet unit contaminated with Staphylococcus aureus has been reported in the UK since universal screening of platelet concentrates using an automated culture method was implemented in 2011. However, in this period there have been three near misses where bacterial contamination with S. aureus was detected. Transfusion of those units was prevented because the presence of aggregates was noted during visual inspection of the platelet concentrates . Results of platelet screening with automated culture methods have been summarised in a recent review by Benjamin and McDonald and an ISBT Forum on bacterial contamination in platelets . The data were collected from 16 published reports and 18 contributions (from 16 countries), respectively. These studies revealed an incidence of confirmed positive cultures ranging from 0.01% to 0.1%. Septic reactions representing false‐negative culture results were reported at rates of approximately 0.007%.