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Background-In the present study, we compared an automatic external defibrillator (AED) that delivers 150-J biphasic shocks with traditional high-energy (200-to 360-J) monophasic AEDs. Methods and Results-AEDs were prospectively randomized according to defibrillation waveform on a daily basis in 4 emergency medical services systems. Defibrillation efficacy, survival to hospital admission and discharge, return of spontaneous circulation, and neurological status at discharge (cerebral performance category) were compared. Of 338 patients with out-of-hospital cardiac arrest, 115 had a cardiac etiology, presented with ventricular fibrillation, and were shocked with an AED. The time from the emergency call to the first shock was 8.9Ϯ3.0 (meanϮSD) minutes. Conclusions-The 150-J biphasic waveform defibrillated at higher rates, resulting in more patients who achieved a return of spontaneous circulation. Although survival rates to hospital admission and discharge did not differ, discharged patients who had been resuscitated with biphasic shocks were more likely to have good cerebral performance.

Lewis diagrams and the octet rule [1] are central concepts in chemistry. Hypervalent molecules break the octet rule because they contain atoms with more than four electron pairs in their valence shell. [2] To describe them with the Lewis model requires hybridization schemes involving d orbitals (sp 3 d or sp 3 d 2 hybrids). [3, 4] The problem is that the formation of these hybrid orbitals requires large promotion energies. [5] Therefore, the significance of ionic resonance diagrams, which obviate the need for hypervalency, has long been discussed. [4] In this context, the electronic structure of SO 2 has been controversial. SO 2 can be described as a hypervalent molecule (Figure 1, left). Apart from d-orbital hybridization, multiple covalent bonding in SO 2 may be explained by three-center p pp p interactions of the sulfur 3p p orbital with non-bonding oxygen p p electrons (this interpretation goes back to Ref. [6]).However, other non-hypervalent ionic resonance structures can be formulated that preserve the octet rule ( Figure 1).The neutral Lewis structure is thought to be dominant, as the SÀO bond length in SO 2 is shorter than that in sulfur monoxide, SO (1.4299(3) in SO 2 from this study, compared to 1.481 for SO [7] ). The bond dissociation energy is also higher in SO 2 than in SO (547.3(8) kJ mol À1 vs. 517.1(8) kJ mol À1 [8] ). Furthermore, O 3 and O 2 , which are valence-isoelectronic with SO 2 and SO, have no available d orbitals, so they cannot be hypervalent, implying bond orders no higher than 1.5 and 2.0, respectively. This is consistent with the fact that the O À O distance in O 3 (1.2717(2) [9] ) is longer than in O 2 (1.15(8) , [10] 1.207 [7] ), in direct contrast with SO 2 relative to SO. This could support the notion that multiple covalent bonding is significant in SO 2 . Indeed, a large number of textbooks [11,12] adhere to this conclusion; for example, in ref. [12] it is stated that the S À O bond order is "at least 2".The simple empirical analysis above is in sharp contrast to the fact that computational studies have found significant ionic contributions to the SÀO bond, and very little sulfur dorbital participation. [13] Today, there is agreement among theoreticians that the role of d orbitals in the formation of bonds involving second and higher row elements is predominantly one of polarization functions, not of hybridization involving d orbitals. [5,14] In fact, the shorter and stronger bonds in SO 2 compared to SO (which is formally a double bond) support the conclusion that there are significant noncovalent contributions to the bonding. Indeed, calculations employing the electron localization function have shown that the polarity of a bond only depends on the electronegativity differences of the bonded atoms, so that molecules formerly classified as being hypervalent can be readily described with various ionic resonance structures. [15] So from a computational viewpoint, hypervalency is avoided by introducing ionic bonds.Experimentally, it has hitherto been difficult to obtain i...

We propose a structure-based protocol for the development of customized covalent inhibitors. Starting from a known inhibitor, in the first and second steps appropriate substituents of the warhead are selected on the basis of quantum mechanical (QM) computations and hybrid approaches combining QM with molecular mechanics (QM/MM). In the third step the recognition unit is optimized using docking approaches for the noncovalent complex. These predictions are finally verified by QM/MM or molecular dynamic simulations. The applicability of our approach is successfully demonstrated by the design of reversible covalent vinylsulfone-based inhibitors for rhodesain. The examples show that our approach is sufficiently accurate to identify compounds with the desired properties but also to exclude nonpromising ones.

Molecular imprinting in network polymers under high pressure was studied as a means of inducing selective binding sites for molecular recognition. Network polymers of methacrylic acid and ethylene glycol dimethacrylate were prepared in the presence of a template, atrazine or ametryn, by free radical polymerization at either 1 or 1000 bar in three different solvents. After washing, they were chromatographically evaluated for rebinding selectivity. In one case, a significantly stronger rebinding of the template to the polymer prepared at high pressure than to the polymer prepared at normal pressure was observed. On an ametryn-imprinted polymer prepared at 1 bar using 2-propanol as solvent, the capacity factor for ametryn was 2.3, whereas on a polymer prepared at 1000 bar the capacity factor was 3.2. The capacity factors of atrazine on these materials were 1.2 and 1.4, respectively. With atrazine as the template, no pressure effect was observed and the capacity factors were, within the experimental error, the same on the high-pressure and the normal-pressure materials. The polymers were characterized by porosimetry, swelling measurements, IR, and SEM. These data showed that the high-pressure polymers exhibited a more compact structure with lower pore volume, higher density, and higher swelling compared to the polymers prepared at normal pressure. The origin of the pressure effect on selectivity was discussed in terms of the monomer−template association tendency and in terms of polymer morphology.

This study was undertaken to evaluate the diagnostic accuracy and time required by first responders to assess the carotid pulse in potentially pulseless patients. We conducted a prospective, randomized study of first responders (n = 206; four different training levels) and were blinded as to the patients' conditions in the cardiac operating rooms of a university hospital. Sixteen patients underwent coronary artery bypass surgery on nonpulsatile cardiopulmonary bypasses. Carotid pulse check was performed either during pulsatile (spontaneous) or during nonpulsatile (extracorporeal) circulation. Patients' hemodynamic status at the time of assessment, diagnostic accuracy of the first responders, and the time required to diagnose carotid pulsatility or pulselessness were documented. Within 10 secs, only 16.5% of the participants (34 of 206) were able to reach any decision about their patients' pulse status. Assessments that were both rapid and correct (15%, i.e., 31 of 206) occurred almost exclusively in pulsatile patients. Advanced training level shortened the delay to decision and improved its accuracy. However, merely 2% of the participants (1 of 59) correctly recognized a truly pulseless patient within 10 secs. Recognition of pulselessness of the carotid artery by rescuers with basic cardiopulmonary resuscitation training is time-consuming and highly inaccurate. Although the carotid pulse check needs to be taught, its importance in the context of layperson basic life support should be de-emphasized.

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