A series of α7 nicotinic acetylcholine receptor full agonists with a 1,3,4-oxadiazol-2-amine core has been discovered. Early lead 1 was found to have a limited therapeutic index with respect to its ...potential for cardiovascular side effects. Further optimisation of this series led to the identification of 22 a potent full agonist showing efficacy at a dose of 0.1mg/kg in the novel object recognition model of cognition enhancement. Comparison of 1 with 22 demonstrated the latter to have an improved oral pharmacokinetic profile and cardiovascular therapeutic index.
A series of α7 nicotinic acetylcholine receptor full-agonists with a 1,3,4-oxadiazol-2-amine core has been discovered. Systematic exploration of the structure–activity relationships for both α7 ...potency and selectivity with respect to interaction with the hERG channel are described. Further profiling led to the identification of compound 22, a potent full agonist showing efficacy in the novel object recognition model of cognition enhancement.
The Heart Truth® is a national education campaign sponsored by the National Heart, Lung, and Blood Institute of the National Institutes of Health, U.S. Department of Health and Human Services, to ...raise awareness among women that heart disease is their leading cause of death and to motivate them to take action for heart health. Launched in 2002 as a brand-driven social marketing effort, the campaign created the Red Dress as the national symbol for women and heart disease awareness. With the brand as a driving force, the campaign has made substantial progress toward its goal through a three-part implementation strategy: partnership development, media relations and use of social media, and education at the community level. This article reports on the development and results of the campaign's community programs that have delivered its messages and materials locally, especially to African-American and Hispanic women, two groups disproportionately affected by heart disease. Most of the local efforts were a mix of communitywide awareness building and more intensive small-group education. The article reports on lessons learned, including pros and cons of working through national organizations with local infrastructures, the advantage of using existing turnkey materials, and the implications of the choice to use scarce resources for educational programming rather than extensive formal evaluation.
Heat shock protein 70 (HSP70) has been implicated in infection-related processes and has been found in body fluids during infection. This study aimed to determine whether pleural mesothelial cells ...release HSP70 in response to bacterial infection in vitro and in mouse models of serosal infection. In addition, the in vitro cytokine effects of the HSP70 isoform, Hsp72, on mesothelial cells were examined. Further, Hsp72 was measured in human pleural effusions and levels compared between non-infectious and infectious patients to determine the diagnostic accuracy of pleural fluid Hsp72 compared to traditional pleural fluid parameters. We showed that mesothelial release of Hsp72 was significantly raised when cells were treated with live and heat-killed Streptococcus pneumoniae. In mice, intraperitoneal injection of S. pneumoniae stimulated a 2-fold increase in Hsp72 levels in peritoneal lavage (p<0.01). Extracellular Hsp72 did not induce or inhibit mediator release from cultured mesothelial cells. Hsp72 levels were significantly higher in effusions of infectious origin compared to non-infectious effusions (p<0.05). The data establish that pleural mesothelial cells can release Hsp72 in response to bacterial infection and levels are raised in infectious pleural effusions. The biological role of HSP70 in pleural infection warrants exploration.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Methylation analysis with probe PW71 (
D15S63) is an established procedure to test patients suspected of having Prader-Willi syndrome or Angelman syndrome. Using this test, we have identified a 28-kb ...deletion spanning
D15S63 in five independent families. Sequence analysis revealed identical breakpoints in all the families. The haplotype data are compatible with a common ancestral origin of the deletion in at least two families. The deletion was not found in 1,000 unrelated controls. Although the deletion maps within the imprinting-center region, neither maternal nor paternal inheritance of the deletion appears to affect imprinting in proximal 15q. We conclude that the deletion is a rare neutral variant that can lead to false-positive results in the PW71-methylation test.
"This handbook is geared towards the following aims: * Reviewing the state of research on disordered language perception and production in adults and children. * Describing and discussing present ...attempts at modelling human language processing by using linguistic disorders and pathologies as a data base. * Presenting diagnostic and therapeutic concepts. * Pointing out gaps and inconcistencies in current knowledge and theories. In bringing together knowlegde of different sources and disciplines under a common roof, the editors have achieved a comprehensive overview of the state of the art in the field of language pathology. Because of the diversity of the disciplines contributing to this scientific field, the chapters differ clearly in theories and methodologies. Yet this handbook represents a clear and common interdisciplinary contribution to linguistic disorders and pathologies and, furthermore, demonstrates the amount of interdisciplinary interaction still required. We chose this title in order to encompass as broadly as possible abnormalities and alterations of language perception, comprehension and production in adults and children, including nonpathological disorders. This handbook will be of interest to anybody involved with disordered language and/or language and speech disturbances, such as linguists and psychologists working in related research areas or teaching related subjects, scientists analyzing and modelling linguistic and cognitive processes (e.g. in Cognitive Psychology, Psycholinguistics, Neurolinguistics, Neuropsychology, Behavioural Neurology, Artificial Intelligence Research, and Cognitive Science), clinicians dealing with aquired or developmental language disorders, and speech pathologists and therapists. Besides presenting the state of the art, the handbook provides rich bibliographical information for research workers, clinicians, and advanced students."
Mar 1, 2002 EDITOR-Freeman and Sweeney's paper on why general practitioners do not implement evidence highlights the importance of good knowledge management for primary care and the weakness of ...relying solely on the dissemination of evidence based medicine. 1 Evidence based medicine is an explicit and highly formalised form of knowledge made available though journals, websites, and lectures. What seems to be lacking is a language for valuing and externalising the tacit knowledge possessed by primary care professionals. 3 The paper lends support to the argument that primary care organisations need to have knowledge management strategies that aren't simply about delivering explicit formalised knowledge.
fraud flourishes in bad times Temple-Cole, John; Burnham, Sally
Charter,
02/2009, Letnik:
80, Številka:
1
Trade Publication Article
The current brush with recession means that we may see a raft of financial statement fraud cases brought about by the need for self-preservation. Companies and their boards are likely to face some ...hard choices when deciding whether to commit those resources to the investigation of internal financial statement fraud cases. There has been something of a ground swell in recent months over the extent to which investors and others can rely on the accuracy of financial statements, which will no doubt heighten the call for reviews or amendments to accounting practices or standards. if organisations do not effectively close down the opportunity by ensuring internal controls are rigorous, then the prevalence of this kind of fraud is likely to increase. Those charged with the governance of an organisation face a difficult dilemma. On the one hand, expenditure on fraud investigation may be seen by some as non-essential when faced with the current restrictions on cash flow. However, failure to uncover and stem the occurrence of fraud may very well contribute to making permanent an organisation's precarious financial state.
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