Collaborative research between clinicians and researchers: a multiple case study of implementation

<p>Abstract</p> <p>Background</p> <p>Bottom-up, clinician-conceived and directed clinical intervention research, coupled with collaboration from researcher experts, is conceptually endorsed by the participatory research movement. This report presents the findings of an evaluation of a program in the Veterans Health Administration meant to encourage clinician-driven research by providing resources believed to be critical. The evaluation focused on the extent to which funded projects: maintained integrity to their original proposals; were methodologically rigorous; were characterized by collaboration between partners; and resulted in sustained clinical impact.</p> <p>Methods</p> <p>Researchers used quantitative (survey and archival) and qualitative (focus group) data to evaluate the implementation, evaluation, and sustainability of four clinical demonstration projects at four sites. Fourteen research center mentors and seventeen clinician researchers evaluated the level of collaboration using a six-dimensional model of participatory research.</p> <p>Results</p> <p>Results yielded mixed findings. Qualitative and quantitative data suggested that although the process was collaborative, clinicians' prior research experience was critical to the quality of the projects. Several challenges were common across sites, including subject recruitment, administrative support and logistics, and subsequent dissemination. Only one intervention achieved lasting clinical effect beyond the active project period. Qualitative analyses identified barriers and facilitators and suggested areas to improve sustainability.</p> <p>Conclusions</p> <p>Evaluation results suggest that this participatory research venture was successful in achieving clinician-directed collaboration, but did not produce sustainable interventions due to such implementation problems as lack of resources and administrative support.</p

Reengineering the clinical research enterprise to involve more community clinicians

<p>Abstract</p> <p>Background</p> <p>The National Institutes of Health has called for expansion of practice-based research to improve the clinical research enterprise.</p> <p>Methods</p> <p>This paper presents a model for the reorganization of clinical research to foster long-term participation by community clinicians.</p> <p>Based on the literature and interviews with clinicians and other stakeholders, we posited a model, conducted further interviews to test the viability of the model, and further adapted it.</p> <p>Results</p> <p>We propose a three-dimensional system of checks and balances to support community clinicians using research support organizations, community outreach, a web-based registry of clinicians and studies, web-based training services, quality audits, and a feedback mechanism for clinicians engaged in research.</p> <p>Conclusions</p> <p>The proposed model is designed to offer a systemic mechanism to address current barriers that prevent clinicians from participation in research. Transparent mechanisms to guarantee the safety of patients and the integrity of the research enterprise paired with efficiencies and economies of scale are maintained by centralizing some of the functions. Assigning other responsibilities to more local levels assures flexibility with respect to the size of the clinician networks and the changing needs of researchers.</p

Cnidocyte discharge is regulated by light and opsin-mediated phototransduction

Cnidocyte discharge is regulated by light and opsin-mediated phototransduction Plachetzki et al. Plachetzki et al. BMC Biology 2012, 10:1

A community based participatory approach to improving health in a Hispanic population

ABSTRACT: BACKGROUND: The Charlotte-Mecklenburg region has one of the fastest growing Hispanic communities in the country. This population has experienced disparities in health outcomes and diminished ability to access healthcare services. This city is home to an established practice-based research network (PBRN) that includes community representatives, health services researchers, and primary care providers. The aims of this project are: to use key principles of community-based participatory research (CBPR) within a practice-based research network (PBRN) to identify a single disease or condition that negatively affects the Charlotte Hispanic community; to develop a community-based intervention that positively impacts the chosen condition and improves overall community health; and to disseminate findings to all stakeholders. METHODS/DESIGN: This project is designed as CBPR. The CBPR process creates new social networks and connections between participants that can potentially alter patterns of healthcare utilization and other health-related behaviors. The first step is the development of equitable partnerships between community representatives, providers, and researchers. This process is central to the CBPR process and will occur at three levels -- community members trained as researchers and outreach workers, a community advisory board (CAB), and a community forum. Qualitative data on health issues facing the community -- and possible solutions -- will be collected at all three levels through focus groups, key informant interviews and surveys. The CAB will meet monthly to guide the project and oversee data collection, data analysis, participant recruitment, implementation of the community forum, and intervention deployment. The selection of the health condition and framework for the intervention will occur at the level of a community-wide forum. Outcomes of the study will be measured using indicators developed by the participants as well as geospatial modeling.On completion, this study will: determine the feasibility of the CBPR process to design interventions; demonstrate the feasibility of geographic models to monitor CBPR-derived interventions; and further establish mechanisms for implementation of the CBPR framework within a PBRN

Structural basis for native agonist and synthetic inhibitor recognition by the Pseudomonas aeruginosa quorum sensing regulator PqsR (MvfR)

Bacterial populations co-ordinate gene expression collectively through quorum sensing (QS), a cell-to-cell communication mechanism employing diffusible signal molecules. The LysR-type transcriptional regulator (LTTR) protein PqsR (MvfR) is a key component of alkyl-quinolone (AQ)-dependent QS in Pseudomonas aeruginosa. PqsR is activated by 2-alkyl-4-quinolones including the Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4(1H)-quinolone), its precursor 2-heptyl-4- hydroxyquinoline (HHQ) and their C9 congeners, 2-nonyl-3-hydroxy-4(1H)-quinolone (C9-PQS) and 2-nonyl-4-hydroxyquinoline (NHQ). These drive the autoinduction of AQ biosynthesis and the up-regulation of key virulence determinants as a function of bacterial population density. Consequently, PqsR constitutes a potential target for novel antibacterial agents which attenuate infection through the blockade of virulence. Here we present the crystal structures of the PqsR co-inducer binding domain (CBD) and a complex with the native agonist NHQ. We show that the structure of the PqsR CBD has an unusually large ligand-binding pocket in which a native AQ agonist is stabilized entirely by hydrophobic interactions. Through a ligand-based design strategy we synthesized and evaluated a series of 50 AQ and novel quinazolinone (QZN) analogues and measured the impact on AQ biosynthesis, virulence gene expression and biofilm development. The simple exchange of two isosteres (OH for NH2) switches a QZN agonist to an antagonist with a concomitant impact on the induction of bacterial virulence factor production. We also determined the complex crystal structure of a QZN antagonist bound to PqsR revealing a similar orientation in the ligand binding pocket to the native agonist NHQ. This structure represents the first description of an LTTR-antagonist complex. Overall these studies present novel insights into LTTR ligand binding and ligand-based drug design and provide a chemical scaffold for further anti-P. aeruginosa virulence drug development by targeting the AQ receptor PqsR

P2 receptors are involved in the mediation of motivation-related behavior

The importance of purinergic signaling in the intact mesolimbic–mesocortical circuit of the brain of freely moving rats is reviewed. In the rat, an endogenous ADP/ATPergic tone reinforces the release of dopamine from the axon terminals in the nucleus accumbens as well as from the somatodendritic region of these neurons in the ventral tegmental area, as well as the release of glutamate, probably via P2Y1 receptor stimulation. Similar mechanisms may regulate the release of glutamate in both areas of the brain. Dopamine and glutamate determine in concert the activity of the accumbal GABAergic, medium-size spiny neurons thought to act as an interface between the limbic cortex and the extrapyramidal motor system. These neurons project to the pallidal and mesencephalic areas, thereby mediating the behavioral reaction of the animal in response to a motivation-related stimulus. There is evidence that extracellular ADP/ATP promotes goal-directed behavior, e.g., intention and feeding, via dopamine, probably via P2Y1 receptor stimulation. Accumbal P2 receptor-mediated glutamatergic mechanisms seem to counteract the dopaminergic effects on behavior. Furthermore, adaptive changes of motivation-related behavior, e.g., by chronic succession of starvation and feeding or by repeated amphetamine administration, are accompanied by changes in the expression of the P2Y1 receptor, thought to modulate the sensitivity of the animal to respond to certain stimuli