Improving survival in out of hospital cardiac arrest a prospective synthesis of best practice

Cardiac arrest is the leading cause of death in the United States. By reviewing and analyzing the successes and failures of resuscitation efforts, it has been possible to identify critical components which have come to be known as the “Chain of Survival:” Early Recognition, Early CPR, Early Defibrillation, Early ALS, and Early Post Resuscitative Care. A failure in any one of the five links will result in a failed resuscitation. Early Recognition is the beginning of the resuscitation effort and includes a number of related components. Witnessed cardiac arrests, those that are seen or heard to occur, have a significantly higher chance of survival than those which are unwitnessed. Properly identifying agonal gasps: irregular, forceful, reflexive breaths which can occur during cardiac arrest, is key to recognition of arrest and activation of the emergency response system. Emergency dispatchers trained to recognize cardiac arrest, as well as to initiate Early CPR via telephonic instruction, have been identified as key personnel in the resuscitation effort. Once professional rescuers have been dispatched, response delays due to distance and traffic can be costly. The use of new technologies like GPS and traffic signal preemption (as well as the use of Police, Fire and EMS in conjunction) has been shown to make it possible to get qualified persons to the scene of a cardiac arrest more safely and more quickly. Once on scene, early, high quality CPR has been shown to dramatically improve survival. After just 8 minutes without assistance, a victim of cardiac arrest has a near zero percent chance of survival. CPR of high quality has been shown to help maintain survivability until more definitive care can be obtained. Early Defibrillation is another key component to survival in many cardiac arrests. While CPR can sustain organ function briefly, cardiac arrest is rarely reversed without defibrillation. Increasingly widespread prevalence of public automated external defibrillators (AEDs) has made Early Defibrillation easier. Furthermore, increased use of AEDs by lay and professional rescuers has called into question the value of more traditional, higher risk interventions like intubation and medication administration. Early ALS interventions have been a staple of resuscitation for decades, but there is little data to support the use of these interventions during cardiac arrest. Early Post-Resuscitative Care, however, has been shown to be an area where invasive ALS interventions can and do make a difference in improved survival. By looking at the body of research for links in the Chain of Survival, opportunities for improvement of resuscitation were identified. Persons who spend significant time around an individual at high risk for heart disease should be educated on possible precipitating symptoms of a myocardial infarct or other early signs of potential cardiac arrest. Persons likely to encounter a cardiac arrest should likewise be trained not only in how to recognize cardiac arrest (through the combination of unresponsiveness and abnormal breathing) but also to initiate basic care via compressions-only CPR. Emergency dispatchers should be increasingly trained to recognize cardiac arrest, as well how to effectively provide dispatcher assisted CPR. The focus of these efforts should be high quality CPR and the early deployment of defibrillation. The use of AEDs by bystanders should be encouraged whenever possible. The emphasis on CPR and use of an AED should be paramount, with invasive ALS interventions eschewed for the simpler and more effective therapies. Once ROSC has been obtained, the use of ALS interventions in unstable patients has been shown not only to prevent death due to transient hemodynamic instability, but also to improve the likelihood of survival with little to no neurological deficit. By embracing the chain of survival, and identifying the critical areas in need of research and improvement, it is possible to provide recommendations that may lead to improved survival from cardiac arrest

The Clinical Promise of Biomarkers of Synapse Damage or Loss in Alzheimer’s Disease

BACKGROUND: Synapse damage and loss are fundamental to the pathophysiology of Alzheimer's disease (AD) and lead to reduced cognitive function. The goal of this review is to address the challenges of forging new clinical development approaches for AD therapeutics that can demonstrate reduction of synapse damage or loss. The key points of this review include the following: Synapse loss is a downstream effect of amyloidosis, tauopathy, inflammation, and other mechanisms occurring in AD.Synapse loss correlates most strongly with cognitive decline in AD because synaptic function underlies cognitive performance.Compounds that halt or reduce synapse damage or loss have a strong rationale as treatments of AD.Biomarkers that measure synapse degeneration or loss in patients will facilitate clinical development of such drugs.The ability of methods to sensitively measure synapse density in the brain of a living patient through synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) imaging, concentrations of synaptic proteins (e.g., neurogranin or synaptotagmin) in the cerebrospinal fluid (CSF), or functional imaging techniques such as quantitative electroencephalography (qEEG) provides a compelling case to use these types of measurements as biomarkers that quantify synapse damage or loss in clinical trials in AD. CONCLUSION: A number of emerging biomarkers are able to measure synapse injury and loss in the brain and may correlate with cognitive function in AD. These biomarkers hold promise both for use in diagnostics and in the measurement of therapeutic successes

Magnetic coupling in a hybrid Mn(ii) acetylene dicarboxylate

The design of ligands that mediate through-bond long range super-exchange in metal–organic hybrid materials would expand chemical space beyond the commonly observed short range, low temperature magnetic ordering. Here we examine acetylene dicarboxylate as a potential ligand that could install long range magnetic ordering due to its spatially continuous frontier orbitals. Using a known Mn(II)-containing coordination polymer we compute and measure the electronic structure and magnetic ordering. In this case, the latter is weak owing to the sub-optimal ligand coordination geometry, with a critical temperature of 2.5 K

A rapidly-reversible absorptive and emissive vapochromic Pt(II) pincer based chemical sensor

Selective, robust and cost-effective chemical sensors for detecting small volatile-organic compounds (VOCs) have widespread applications in industry, healthcare and environmental monitoring. Here we design a Pt(II) pincer-type material with selective absorptive and emissive responses to methanol and water. The yellow anhydrous form converts reversibly on a subsecond timescale to a red hydrate in the presence of parts-per-thousand levels of atmospheric water vapour. Exposure to methanol induces a similarly-rapid and reversible colour change to a blue methanol solvate. Stable smart coatings on glass demonstrate robust switching over 104 cycles, and flexible microporous polymer membranes incorporating microcrystals of the complex show identical vapochromic behaviour. The rapid vapochromic response can be rationalized from the crystal structure, and in combination with quantum-chemical modelling we provide a complete microscopic picture of the switching mechanism. We discuss how this multiscale design approach can be used to obtain new compounds with tailored VOC selectivity and spectral responses

Prototyping a geospatial Atlas for wildfire planning and management

Includes bibliographical references (pages 14-17).Wildland fire managers are increasingly embracing risk management principles by being more anticipatory, proactive, and “engaging the fire before it starts”. This entails investing in pre-season, cross-boundary, strategic fire response planning with partners and stakeholders to build a shared understanding of wildfire risks and management opportunities. A key innovation in planning is the development of potential operational delineations (PODs), i.e., spatial management units whose boundaries are relevant to fire containment operations (e.g., roads, ridgetops, and fuel transitions), and within which potential fire consequences, suppression opportunities/challenges, and strategic response objectives can be analyzed to inform fire management decision making. As of the summer of 2020, PODs have been developed on more than forty landscapes encompassing National Forest System lands across the western USA, providing utility for planning, communication, mitigation prioritization, and incident response strategy development. Here, we review development of a decision support tool—a POD Atlas—intended to facilitate cross-boundary, collaborative strategic wildfire planning and management by providing high-resolution information on landscape conditions, values at risk, and fire management resource needs for individual PODs. With the atlas, users can rapidly access and assimilate multiple forms of pre-loaded data and analytics in a customizable manner. We prototyped and operationalized this tool in concert with, and for use by, fire managers on several National Forests in the Southern Rocky Mountains of the USA. We present examples, discuss real-world use cases, and highlight opportunities for continued decision support improvement

Estrogen receptor dependent inhibitors of NF-κB transcriptional activation-1 synthesis and biological evaluation of substituted 2-cyanopropanoic acid derivatives : pathway selective inhibitors of NF-κB, a potential treatment for rheumatoid arthritis

Pathway selective ligands of the estrogen receptor inhibit transcriptional activation of proinflammatory genes mediated by NF-kappaB. Substituted 2-cyanopropanoic acid derivatives were developed leading to the discovery of WAY-204688, an orally active, pathway selective, estrogen receptor dependent anti-inflammatory agent. This propanamide was shown to be orally active in preclinical models of inflammatory diseases, such as rheumatoid arthritis, without the proliferative effect associated with traditional estrogens