Excited Delirium Syndrome (ExDS): defining based on a review of the literature.

BACKGROUND: Patients present to police, Emergency Medical Services, and the emergency department with aggressive behavior, altered sensorium, and a host of other signs that may include hyperthermia, "superhuman" strength, diaphoresis, and lack of willingness to yield to overwhelming force. A certain percentage of these individuals will go on to expire from a sudden cardiac arrest and death, despite optimal therapy. Traditionally, the forensic community would often classify these as "Excited Delirium" deaths. OBJECTIVES: This article will review selected examples of the literature on this topic to determine if it is definable as a discrete medical entity, has a recognizable history, epidemiology, clinical presentation, pathophysiology, and treatment recommendations. DISCUSSION: Excited delirium syndrome is characterized by delirium, agitation, acidosis, and hyperadrenergic autonomic dysfunction, typically in the setting of acute-on-chronic drug abuse or serious mental illness or a combination of both. CONCLUSIONS: Based upon available evidence, it is the consensus of an American College of Emergency Physicians Task Force that Excited Delirium Syndrome is a real syndrome with uncertain, likely multiple, etiologies.

Feedback control system simulator for the control of biological cells in microfluidic cross slots and integrated microfluidic systems.

Control systems for lab on chip devices require careful characterisation and design for optimal performance. Traditionally, this involves either extremely computationally expensive simulations or lengthy iteration of laboratory experiments, prototype design, and manufacture. In this paper, an efficient control simulation technique, valid for typical microchannels, Computed Interpolated Flow Hydrodynamics (CIFH), is described that is over 500 times faster than conventional time integration techniques. CIFH is a hybrid approach, utilising a combination of pre-computed flows and hydrodynamic equations and allows the efficient simulation of dynamic control systems for the transport of cells through micro-fluidic devices. The speed-ups achieved by using pre-computed CFD solutions mapped to an n-dimensional control parameter space, significantly accelerate the evaluation and improvement of control strategies and chip design. Here, control strategies for a naturally unstable device geometry, the microfluidic cross-slot, have been simulated and optimal parameters have been found for proposed devices capable of trapping and sorting cells.

Facile scalable reduction of N-acylated dihydropyrazoles.

The reduction of a variety of highly functionalized N-acylated dihydropyrazoles (1) with BH3 x pyridine is described. The process through which this unexpectedly difficult reduction was discovered and developed is reported. A facile atom-efficient route to the N-acylated dihydropyrazole reduction precursors (1) is also illustrated. The resulting acylpyrazolidine products (2) that arise upon reduction were isolated in good to high yields following exposure to reaction conditions which have been shown to tolerate a variety of different functional groups. Finally, this route has been demonstrated on a kilogram scale and provides direct access to potential proline surrogates for peptidomimetic applications.

Asymmetric carbon-carbon bond formations in conjugate additions of lithiated N-Boc allylic and benzylic amines to nitroalkenes: enantioselective synthesis of substituted piperidines, pyrrolidines, and pyrimidinones.

(-)-Sparteine mediated lithiations of N-Boc-allylic and benzylic amines provide configurationally stable intermediates which on conjugate additions to nitroalkenes provide highly enantioenriched enecarbamate products in good yields, and with high diastereoselectivities. Straightforward transformations of these adducts offer general routes to substituted 3,4-substituted piperidines, 3,4-substituted pyrrolidines, and 4,5-substituted pyrimidinones. Diastereoselective substitutions of intermediate lactams followed by reduction provide 3,4,5-substituted piperidines and 3,4-trisubstituted pyrrolidines. Lithiation adjacent to nitrogen of 3,4-substituted piperidines and pyrrolidines followed by diastereoselective substitution opens a route to 2,4,5- and 2,4,5,6-substituted piperidines as well as 2,3,4- and 2,3,4,5-substituted pyrrolidines. The enantiomers of the enecarbamate and 3,4-substituted piperidine products may be accessed by stannylation/transmetalation sequences as well as by further manipulation of 4-substituted piperidones. The methodology is used to synthesize both enantiomers of an aspartic peptidase inhibitor intermediate, 3-hydroxy-4-phenylpiperidine, as well as the antidepressant (+)-femoxetine.

Asymmetric carbon-carbon bond formations by conjugate additions of lithiated N-boc allylic amines to nitroalkenes: enantioselective synthesis of functionalized cyclopentanoids.

[reaction: see text] Allylic organolithiums generated by enantioselective deprotonation of N-Boc-N-(p-methoxyphenyl) allylic amines undergo conjugate additions with nitroalkenes to provide enecarbamates containing two contiguous stereogenic centers in good yields with high diastereoselectivities and enantioselectivities. Further elaboration of these adducts to enantioenriched substituted cyclopentanones and aminocyclopentanes is reported.