Clinical Trials

The clinical practice of resuscitation science is dependent on discoveries generated in the basic science and animal laboratory and then translated into clinical trials for application in humans. The successful implementation of prospective, randomized, controlled, clinical trials in the field of cardiac arrest remains challenging and continues to evolve. Funding for clinical trials of cardiac arrest is limited, and there are significant obstacles to performing such studies because of the inability to obtain informed consent under these emergency circumstances. The absence of reliable national statistics on cardiac arrest, evaluation of neurological outcome, and potential confounders such as post-resuscitation hospital-based care and quality of cardiopulmonary resuscitation (CPR) continue to challenge cardiac arrest clinical trials. Nonetheless, the immense public health burden of cardiac arrest is being recognized, appropriate public health initiatives to address the problem are being implemented, and the resuscitation research community is meeting this challenge

Mixing-induced anisotropic correlations in molecular crystalline systems

We investigate the structure of mixed thin films composed of pentacene (PEN) and diindenoperylene (DIP) using X-ray reflectivity and grazing incidence X-ray diffraction. For equimolar mixtures we observe vanishing in-plane order coexisting with an excellent out-of-plane order, a yet unreported disordering behavior in binary mixtures of organic semiconductors, which are crystalline in their pure form. One approach to rationalize our findings is to introduce an anisotropic interaction parameter in the framework of a mean field model. By comparing the structural properties with those of other mixed systems, we discuss the effects of sterical compatibility and chemical composition on the mixing behavior, which adds to the general understanding of interactions in molecular mixtures.Comment: 5 pages, 5 figures, accepted by Phys. Rev. Let

Electron capture on iron group nuclei

We present Gamow-Teller strength distributions from shell model Monte Carlo studies of fp-shell nuclei that may play an important role in the pre-collapse evolution of supernovae. We then use these strength distributions to calculate the electron-capture cross sections and rates in the zero-momentum transfer limit. We also discuss the thermal behavior of the cross sections. We find large differences in these cross sections and rates when compared to the naive single-particle estimates. These differences need to be taken into account for improved modeling of the early stages of type II supernova evolution

Localization of tenascin in human skin wounds

A total of 56 surgically treated human skin wounds with a wound age between 8h and 7 months were investigated. Tenascin was visualized by immunohistochemistry and appeared first in the wound area pericellularly around fibroblastic cells approximately 2 days after wounding. A network-like interstitial positive staining pattern was first detectable in 3-day-old skin wounds. In all wounds with an age of 5 days or more, intensive reactivity for tenascin could be observed in the lesional area (dermal-epidermal junction, wound edge, areas of bleeding). In wounds with an age of more than approximately 1.5 months no positive staining occurred in the scar tissue. In conclusion, for forensic purposes, positive staining for tenascin restricted to the pericellular area of fibroblastic cells indicates a wound age of at least 2 days. Network-like structures appear after approximately 3 days or more. Since tenascin seems to be regularly detectable in skin wounds older than 5 days, the lack of a positive reaction in a sufficient number of specimens indicates a wound age of less than 5 days. The lack of a positive reaction in the granulation tissue of wounds with advanced wound age indicates a survival time of more than about 1.5 months, but a positive staining in older wounds cannot be excluded

Gamow-Teller strength distributions in fp-shell nuclei

We use the shell model Monte Carlo method to calculate complete 0f1p-shell response functions for Gamow-Teller (GT) operators and obtain the corresponding strength distributions using a Maximum Entropy technique. The approach is validated against direct diagonalization for 48Ti. Calculated GT strength distributions agree well with data from (n,p) and (p,n) reactions for nuclei with A=48-64. We also calculate the temperature evolution of the GT+ distributions for representative nuclei and find that the GT+ distributions broaden and the centroids shift to lower energies with increasing temperature

Half-lives and pre-supernova weak interaction rates for nuclei away from the stability line

A detailed model for the calculation of beta decay rates of the $fp$ shell nuclei for situations prevailing in pre-supernova and collapse phases of evolution of the core of massive stars leading to supernova explosion has been extended for electron-capture rates. It can also be used to determine the half-lives of neutron-rich nuclei in the $fp/fpg$ shell. The model uses an averaged Gamow-Teller (GT) strength function. But it can also use the experimental log ft values and GT strength function from $(n,p)$ reaction studies wherever available. The calculated rate includes contributions from each of the low-lying excited states of the mother including some specific resonant states ("back resonance") having large GT matrix elements.Comment: 11 pages; Latex; no figs; version to appear in J. Phys.

The Role of Electron Captures in Chandrasekhar Mass Models for Type Ia Supernovae

The Chandrasekhar mass model for Type Ia Supernovae (SNe Ia) has received increasing support from recent comparisons of observations with light curve predictions and modeling of synthetic spectra. It explains SN Ia events via thermonuclear explosions of accreting white dwarfs in binary stellar systems, being caused by central carbon ignition when the white dwarf approaches the Chandrasekhar mass. As the electron gas in white dwarfs is degenerate, characterized by high Fermi energies for the high density regions in the center, electron capture on intermediate mass and Fe-group nuclei plays an important role in explosive burning. Electron capture affects the central electron fraction Y_e, which determines the composition of the ejecta from such explosions. Up to the present, astrophysical tabulations based on shell model matrix elements were only available for light nuclei in the sd-shell. Recently new Shell Model Monte Carlo (SMMC) and large-scale shell model diagonalization calculations have also been performed for pf-shell nuclei. These lead in general to a reduction of electron capture rates in comparison with previous, more phenomenological, approaches. Making use of these new shell model based rates, we present the first results for the composition of Fe-group nuclei produced in the central regions of SNe Ia and possible changes in the constraints on model parameters like ignition densities and burning front speeds.Comment: 26 pages, 8 figures, submitted to Ap

Emerging mechanistic insights into AAA complexes regulating proteasomal degradation.

The 26S proteasome is an integral element of the ubiquitin-proteasome system(UPS) and, as such, responsible for regulated degradation of proteins in eukaryotic cells.It consists of the core particle, which catalyzes the proteolysis of substrates into small peptides, and the regulatory particle, which ensures specificity for a broad range of substrates.The heart of the regulatory particle is an AAA-ATPase unfoldase, which is surrounded by non-ATPase subunits enabling substrate recognition and processing. Cryo-EM-based studies revealed the molecular architecture of the 26S proteasome and its conformational rearrangements, providing insights into substrate recognition, commitment, deubiquitylation and unfolding. The cytosol proteasomal degradation of polyubiquitylated substrates is tuned by various associating cofactors, including deubiquitylating enzymes, ubiquitin ligases,shuttling ubiquitin receptors and the AAA-ATPase Cdc48/p97. Cdc48/p97 and its cofactors function upstream of the 26S proteasome, and their modular organization exhibits some striking analogies to the regulatory particle. In archaea PAN, the closest regulatory particle homolog and Cdc48 even have overlapping functions, underscoring their intricate relationship.Here, we review recent insights into the structure and dynamics of the 26S proteasome and its associated machinery, as well as our current structural knowledge on the Cdc48/p97 and its cofactors that function in the ubiquitin-proteasome system (UPS)

Better Junction Control with Bus Priority

The problem was to design a traffic light controller for a set of neigh- bouring junctions, which gives priority to incoming buses while ensuring a degree of fairness to the general traffic. The team has developed three complementary approaches, that present different strengths and weaknesses and might be applicable in different junction configurations or traffic conditions: 1. A continuous-variable, discrete-time optimisation approach for de- termining the fraction of green time to give to each arm of a junc- tion during the next traffic light cycle, in order to minimise total weighted squared vehicle waiting times, with more weight on buses than on cars. 2. A piece-wise linear ordinary differential equation model of queue length dynamics on a junction arm, based on flux of vehicles into and out of that arm. 3. Adiscrete-variable,discrete-timeMarkovDecisionProcessapproach. The state of the system is comprised of vehicle queue lengths and the junction’s current stage. The action is to stay in the current stage or move to the next stage. An optimal policy minimises long run expected discounted weighted delay

Implementing the 2005 American Heart Association guidelines, including use of the impedance threshold device, improves hospital discharge rate after in-hospital cardiac arrest

OBJECTIVE: To determine the impact of the 2005 American Heart Association cardiopulmonary resuscitation (CPR) guidelines, including use of an impedance threshold device (ITD), on survival after in-hospital cardiac arrest. METHODS: Two community hospitals that tracked outcomes after in-hospital cardiac arrest pooled and compared their hospital discharge rate before and after implementing the 2005 American Heart Association CPR guidelines (including ITD) in standardized protocols. In CPR we used the proper ventilation rate, allowed full chest-wall recoil, conducted continuous CPR following intubation, and used an ITD. We compared historical control data from a 12-month period at St Cloud Hospital, St Cloud, Minnesota, to data from a subsequent 18-month intervention phase. We compared historical control data from a 12-month period at St Dominic Hospital, Jackson, Mississippi to a subsequent 12-month intervention phase. 507 patients received CPR during the study period. Patient age and sex were similar in the control and intervention groups. RESULTS: The combined hospital discharge rate for patients with an in-hospital cardiac arrest was 17.5% in the control group (n=246 patients), which is similar to the national average, versus 28% in the intervention group (n=261 patients) (P=.006, odds ratio 1.83, 95% CI 1.17-2.88). The greatest benefit of the intervention was in patients with an initial rhythm of pulseless electrical activity: 14.4% versus 29.7% (P=.014, odds ratio 2.50, 95% CI 1.15, 5.58). Neurological function (as measured with the Cerebral Performance Category scale) in survivors at hospital discharge was similar between the groups. CONCLUSIONS: Implementation of improved ways to increase circulation during CPR increased the in-hospital discharge rate by 60%, compared to historical controls in 2 community hospitals. These data demonstrate that immediate care with improved means to circulate blood during CPR significantly reduces hospital mortality from inhospital sudden cardiac arrest