A Computational Investigation of Cardiac Caveolae as a Source of Persistent Sodium Current

Recent studies of cholesterol-rich membrane microdomains, called caveolae, reveal that caveolae are reservoirs of “recruitable” sodium ion channels. Caveolar channels constitute a substantial and previously unrecognized source of sodium current in cardiac cells. In this paper we model for the first time caveolar sodium currents and their contributions to cardiac action potential morphology. We show that the β-agonist-induced opening of caveolae may have substantial impacts on peak overshoot, maximum upstroke velocity, and ultimately conduction velocity. Additionally, we show that prolonged action potentials and the formation of potentially arrhythmogenic afterdepolarizations, can arise if caveolae open intermittently throughout the action potential. Our simulations suggest that caveolar sodium current may constitute a route, which is independent of channelopathies, to delayed repolarization and the arrhythmias associated with such delays

Use of policy, education, and enforcement to reduce binge drinking among university students: The NU Directions project

This paper describes a program, conducted over a 5-year period, that effectively reduced heavy drinking and alcohol-related harms among university students. The program was organized around strategies to change the environment in which binge drinking occurred and involved input and cooperation from officials and students of the university, representatives from the city and the neighborhood near the university, law enforcement, as well as public health and medical officials. In 1997, 62.5% of the university’s approximately 16,000 undergraduate student population reported binge drinking. This rate had dropped to 47% in 2003. Similar reductions were found in both self-reported primary and secondary harms related to alcohol consumption

Cluster analysis of the origins of the new influenza A(H1N1) virus

In March and April 2009, a new strain of influenza A(H1N1) virus has been isolated in Mexico and the United States. Since the initial reports more than 10,000 cases have been reported to the World Health Organization, all around the world. Several hundred isolates have already been sequenced and deposited in public databases. We have studied the genetics of the new strain and identified its closest relatives through a cluster analysis approach. We show that the new virus combines genetic information related to different swine influenza viruses. Segments PB2, PB1, PA, HA, NP and NS are related to swine H1N2 and H3N2 influenza viruses isolated in North America. Segments NA and M are related to swine influenza viruses isolated in Eurasia

Inverting the patient involvement paradigm: defining patient led research.

PLAIN ENGLISH SUMMARY: Patients usually understand their disease and lifestyle needs better than many medical professionals. They also have important ideas about what research would be most beneficial to their lives, especially on how to manage symptoms in a way that improves daily quality of life. In the UK, the National Institute for Health Research has recognised the value of patient insight, and now requires researchers with public funding to involve patients and the public throughout the research process. There are many opportunities for involvement, but these generally focus on improving study design to ensure the trial is acceptable to participants. Some programmes work towards setting research priorities as important to patients, public members, and medical experts, but due to the complexity and cost involved in running clinical trials, the majority of research originates with the pharmaceutical industry or academic institutions. There is a clear mismatch between research ideas that patients prioritise (quality of life), and those actually investigated (drug development).The Patient Led Research Hub (PLRH) is a new initiative hosted by the Cambridge Clinical Trials Unit. The PLRH supports research ideas as proposed by patient organisations, providing resources and expertise in research design and delivery. The PLRH aims to co-produce any technically feasible project, regardless of disease or symptom focus. The proposing patient group maintains ownership of the project with an active role in study management. This method of research has proven to produce credible research studies that are of direct relevance to patients. ABSTRACT: Patient and Public Involvement has become an indispensable and expected component of healthcare research in the United Kingdom, largely driven by the National Institute of Health Research and other research funders. Opportunities for patients to become involved in research abound, and many organisations now have dedicated 'public involvement' teams. However, its value is often questioned amidst criticism of tokenism and the recognition that a mismatch persists between patient priorities and funded research. Although patients are frequently consulted, evidence that their involvement influences the research agenda remains limited. We propose a novel model that allows patients and the public not only to propose research questions, but to design, initiate and deliver their own research with all the necessary support from research professionals. We demonstrate the feasibility and utility of this approach in reporting the establishment, experiences and progress of the Patient Led Research Hub. Using this resource, patient organisations are now able to initiate and conduct rigorous clinical research unfettered by the constraints of academic or economic agendas

Football Game Program 3 1965

Football Game Program 3 196

Verifying Temporal Regular Properties of Abstractions of Term Rewriting Systems

The tree automaton completion is an algorithm used for proving safety properties of systems that can be modeled by a term rewriting system. This representation and verification technique works well for proving properties of infinite systems like cryptographic protocols or more recently on Java Bytecode programs. This algorithm computes a tree automaton which represents a (regular) over approximation of the set of reachable terms by rewriting initial terms. This approach is limited by the lack of information about rewriting relation between terms. Actually, terms in relation by rewriting are in the same equivalence class: there are recognized by the same state in the tree automaton. Our objective is to produce an automaton embedding an abstraction of the rewriting relation sufficient to prove temporal properties of the term rewriting system. We propose to extend the algorithm to produce an automaton having more equivalence classes to distinguish a term or a subterm from its successors w.r.t. rewriting. While ground transitions are used to recognize equivalence classes of terms, epsilon-transitions represent the rewriting relation between terms. From the completed automaton, it is possible to automatically build a Kripke structure abstracting the rewriting sequence. States of the Kripke structure are states of the tree automaton and the transition relation is given by the set of epsilon-transitions. States of the Kripke structure are labelled by the set of terms recognized using ground transitions. On this Kripke structure, we define the Regular Linear Temporal Logic (R-LTL) for expressing properties. Such properties can then be checked using standard model checking algorithms. The only difference between LTL and R-LTL is that predicates are replaced by regular sets of acceptable terms