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Incomplete Knowledge (incomplete + knowledge)
Selected AbstractsElementary Propositions and Essentially Incomplete Knowledge: A Framework for the Interpretation of Quantum MechanicsNOUS, Issue 1 2004William Demopoulos A central problem in the interpretation of non-relativistic quantum mechanics is to relate the conceptual structure of the theory to the classical idea of the state of a physical system. This paper approaches the problem by presenting an analysis of the notion of an elementary physical proposition. The notion is shown to be realized in standard formulations of the theory and to illuminate the significance of proofs of the impossibility of hidden variable extensions. In the interpretation of quantum mechanics that emerges from this analysis, the philosophically distinctive features of the theory derive from the fact that it seeks to represent a reality of which complete knowledge is essentially unattainable. [source] Selection of Antiepileptic Drug Polytherapy Based on Mechanisms of Action: The Evidence ReviewedEPILEPSIA, Issue 11 2000Charles L. P. Deckers Summary: Purpose: When monotherapy with antiepileptic drugs (AEDs) fails, combination therapy is tried in an attempt to improve effectiveness by improving efficacy, tolerability, or both. We reviewed the available studies (both animal and human) on AED polytherapy to determine whether AEDs can be selected for combination therapy based on their mechanisms of action, and if so, which combinations are associated with increased effectiveness. Because various designs and methods of analysis were used in these studies, it was also necessary to evaluate the appropriateness of these approaches. Methods: Published papers reporting on AED polytherapy in animals or humans were identified by Medline search and by checking references cited in these papers. Results: Thirty-nine papers were identified reporting on two-drug AED combinations. Several combinations were reported to offer improved effectiveness, but no uniform approach was used in either animal or human studies for the evaluation of pharmacodynamic drug interactions; efficacy was often the only end point. Conclusions: There is evidence that AED polytherapy based on mechanisms of action may enhance effectiveness. In particular, combining a sodium channel blocker with a drug enhancing GABAergic inhibition appears to be advantageous. Combining two GABA mimetic drugs or combining an AMPA antagonist with an NMDA antagonist may enhance efficacy, but tolerability is sometimes reduced. Combining two sodium channel blockers seems less promising. However, given the incomplete knowledge of the pathophysiology of seizures and indeed of the exact mechanisms of action of AEDs, an empirical but rational approach for evaluating AED combinations is of fundamental importance. This would involve appropriate testing of all possible combinations in animal models and subsequent evaluation of advantageous combinations in clinical trials. Testing procedures in animals should include the isobologram method, and the concept of drug load should be the basis of studies in patients with epilepsy. [source] Mechanisms of nitrate tolerance: potential roles of folateEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2003F. Iachini Bellisarii Abstract More than 100 years since their introduction in cardiovascular therapy, nitrates continue to be widely used in ischaemic heart disease despite incomplete knowledge of their intimate mechanism of action. Particularly, the development of a progressive attenuation of their efficacy over prolonged use (tolerance) continues to be the subject of current investigation. Newer findings point to the role of increased intracellular oxidative stress as a mechanism for tolerance and to folic acid derivatives as pharmacologic means to attenuate its development. This paper reviews nitrate mechanism of action, the history of nitrate tolerance and newer findings related to the use of folate to prevent this phenomenon. [source] Quantifying the impact of groundwater discharge on the surface,subsurface exchangeHYDROLOGICAL PROCESSES, Issue 15 2009Fulvio Boano Abstract The exchange of oxygen and nutrients between the well-aerated stream water and the subsurface water is crucial for the biochemical conditions of the hyporheic zone. The metabolic activity of the hyporheic microorganisms controls the fate of nitrogen and phosphorus in the pore water, and influences the fate of these nutrients at the catchment scale. Unfortunately, the incomplete knowledge of the complex hydrodynamics of the coupled surface-subsurface flow field often hinders the understanding of the ecological relevance of the hyporheic processes. Here, we analyse the influence of groundwater discharge through the streambed on bedform-induced hyporheic exchange. A simple mathematical model of a coupled stream-aquifer system is developed in order to describe the essential feature of the surface-subsurface exchange. The most representative characteristics of the hyporheic exchange, e.g. the depth of the hyporheic zone - are parametrized in terms of a small number of easily measurable quantities. This information on the hyporheic flow field provides the fundamental basis for the study of the ecological function of the hyporheic zone. Copyright © 2009 John Wiley & Sons, Ltd. [source] Phylogenetic relationships within the tropical soft coral genera Sarcophyton and Lobophytum (Anthozoa, Octocorallia)INVERTEBRATE BIOLOGY, Issue 4 2006Catherine S. McFadden Abstract. The alcyonacean soft coral genera Sarcophyton and Lobophytum are conspicuous, ecologically important members of shallow reef communities throughout the Indo-West Pacific. Study of their ecology is, however, hindered by incomplete knowledge of their taxonomy: most species cannot be identified in the field and the two genera cannot always be distinguished reliably. We used a 735-bp fragment of the octocoral-specific mitochondrial protein-coding gene msh1 to construct a phylogeny for 92 specimens identified to 19 species of Lobophytum and 16 species of Sarcophyton. All phylogenetic methods used recovered a tree with three strongly supported clades. One clade included only morphologically typical Sarcophyton species with a stalk distinct from the polypary, poorly formed club-shaped sclerites in the colony surface, and large spindles in the interior of the stalk. A second clade included only morphologically typical Lobophytum colonies with lobes and ridges on the colony surface, poorly formed clubs in the colony surface, and interior sclerites consisting of oval forms with regular girdles of ornamental warts. The third distinct clade included a mix of Sarcophyton and Lobophytum nominal species with intermediate morphologies. Most of the species in this mixed clade had a polypary that was not distinct from the stalk, and the sclerites in the colony surface were clubs with well-defined heads. Within the Sarcophyton clade, specimens identified as Sarcophyton glaucum belonged to six very distinct genetic sub-clades, suggesting that this morphologically heterogeneous species is actually a cryptic species complex. Our results highlight the need for a complete taxonomic revision of these genera, using molecular data to help confirm species boundaries as well as to guide higher taxonomic decisions. [source] A health protection model for Hispanic adults with Type 2 diabetesJOURNAL OF CLINICAL NURSING, Issue 7b 2007Christine L Latham RN Aims., The Hispanic Health Protection Model (HHPM) was designed to assist practitioners' systematic assessment of Hispanic people to establish baselines and evaluate the success of early diabetes treatment. This article provides the research basis of the HHPM and related assessment tools. Background., The treatment of diabetes incorporates lifestyle change, and this adjustment is particularly important to follow with vulnerable groups. One such group is the Hispanic population, since the impact of diabetes is greatest on economically disadvantaged segments of this population, who suffer disproportionately higher Type 2 diabetes prevalence and higher levels of morbidity and mortality as compared with other populations. Traditional Hispanic health beliefs are often in conflict with Western medicine, so the adjustments to the lifestyle demands of this disease need to be evaluated. Methods., To understand this discrepancy fully in patient outcomes, a culturally sensitive assessment framework was developed based on health protection theories and research with Hispanic people with diabetes and, based on this framework, assessment tools were translated for use during interviews with low literacy, Spanish-speaking patients. Conclusions., The HHPM translated measures of premorbid lifestyle, health beliefs, support, self-efficacy, quality of life, knowledge of diabetes, and physiological parameters can be used during consecutive clinic visits during the first six months of therapy to map the success of patients' understanding of and psychological adjustment to diabetes. Relevance to clinical practice., The HHPM is a culturally-relevant, systematic, and holistic approach to assessing adjustment of Hispanic people to a new diagnosis of diabetes, including their psychological, cognitive, and physiological outcomes. Using this type of systematic approach will allow practitioners to target barriers to therapy, such as a lack of self-efficacy or incomplete knowledge of the disease and its treatment in a strategic manner to improve patient success in managing the complex lifestyle changes of diabetes mellitus. [source] In silico prediction and screening of ,-secretase inhibitors by molecular descriptors and machine learning methodsJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 6 2010Xue-Gang Yang Abstract ,-Secretase inhibitors have been explored for the prevention and treatment of Alzheimer's disease (AD). Methods for prediction and screening of ,-secretase inhibitors are highly desired for facilitating the design of novel therapeutic agents against AD, especially when incomplete knowledge about the mechanism and three-dimensional structure of ,-secretase. We explored two machine learning methods, support vector machine (SVM) and random forest (RF), to develop models for predicting ,-secretase inhibitors of diverse structures. Quantitative analysis of the receiver operating characteristic (ROC) curve was performed to further examine and optimize the models. Especially, the Youden index (YI) was initially introduced into the ROC curve of RF so as to obtain an optimal threshold of probability for prediction. The developed models were validated by an external testing set with the prediction accuracies of SVM and RF 96.48 and 98.83% for ,-secretase inhibitors and 98.18 and 99.27% for noninhibitors, respectively. The different feature selection methods were used to extract the physicochemical features most relevant to ,-secretase inhibition. To the best of our knowledge, the RF model developed in this work is the first model with a broad applicability domain, based on which the virtual screening of ,-secretase inhibitors against the ZINC database was performed, resulting in 368 potential hit candidates. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010 [source] Treatment of inflammatory dermatoses by tumour necrosis factor antagonistsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 10 2006A Jacobi Abstract Background, The treatment of inflammatory skin diseases is at present often empirical as causal therapeutic approaches, based on an incomplete knowledge of the immune pathogenesis, are mostly unavailable. The currently applied treatments can in fact lead to remission of the disease; however, under certain circumstances undesirable side-effects must be expected. On the basis of experience gained in cytokine modulation therapy of chronic inflammatory diseases such as rheumatoid arthritis and psoriasis, the application of TNF-, inhibitors represents a novel, more specific, and effective therapeutic option for distinct chronic inflammatory diseases. Patients and methods, The current status of the therapeutic effect of TNF-, blockers is discussed based on our own observations and a review of the current literature. Also discussed are potential undesirable side-effects and possible contraindications of this therapy. Results and conclusions, Based on recent findings, the use of TNF-, blockers seems to be promising in the treatment of therapy-resistant inflammatory dermatoses. At present, guidelines for indications and contraindications of anti-TNF-, treatment of inflammatory skin disorders are rare. Such guidelines are necessary to improve the efficacy of anticytokine treatment and the reduction of side-effects. [source] Proteomics application exercise of the Swiss Proteomics Society: Report of the SPS'02 sessionPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 8 2003Pierre-Alain Binz Abstract After the success of the mass spectrometry (MS) round table that was held at the first Swiss Proteomics Society congress (SPS'01) in Geneva, the SPS has organized a proteomics application exercise and allocated a full session at the SPS'02 congress. The main objective was to encourage the exchange of expertise in protein identification, with a focus on the use of mass spectrometry, and to create a bridge between the users' questions and the instrument providers' solutions. Two samples were sent to fifteen interested labs, including academic groups and MS hardware providers. Participants were asked to identify and partially characterize the samples. They consisted of a complex mixture of peptide/proteins (sample A) and an almost pure recombinant peptide carrying post-translational modifications (sample B). Sample A was an extract of snake venom from the species Bothrops jararaca. Sample B was a recombinant and modified peptide derived from the shrimp Penaeus vannamei penaeidin 3a. The eight labs that returned results reported the use of a wide range of MS instrumentation and techniques. They mentioned a variety of time and manpower allocations. The origin of sample A was generally identified together with a number of database protein entries. The difficulty of the sample identification lay in the incomplete knowledge of the Bothrops species genome sequence and is discussed. Sample B was generally and correctly identified as penaeidin. However, only one group reported the full primary structure. Interestingly, the approaches were again varied and are discussed in the text. [source] When consensus choice dominates individualism: Jensen's inequality and collective decisions under uncertaintyQUANTITATIVE ECONOMICS, Issue 1 2010Charles F. Manski D7; D81; H42 Research on collective provision of private goods has focused on distributional considerations. This paper studies a class of problems of decision under uncertainty in which an efficiency argument for collective choice emerges from the mathematics of aggregating individual payoffs. Consider decision making when each member of a population has the same objective function, which depends on an unknown state of nature. If agents knew the state of nature, they would make the same decision. However, they may have different beliefs or may use different decision criteria to cope with their incomplete knowledge. Hence, they may choose different actions even though they share the same objective. Let the set of feasible actions be convex and the objective function be concave in actions, for all states of nature. Then Jensen's inequality implies that consensus choice of the mean privately chosen action yields a larger mean payoff than does individualistic decision making, in all states of nature. If payoffs are transferable, the mean payoff from consensus choice may be allocated to Pareto dominate individualistic decision making. I develop these ideas. I also use Jensen's inequality to show that a planner with the power to assign actions to the members of the population should not diversify. Finally, I give a version of the collective-choice result that holds with consensus choice of the median rather than mean action. [source] Getting Real Performance Out of Pay-for-PerformanceTHE MILBANK QUARTERLY, Issue 3 2008SEAN NICHOLSON Context: Most private and public health insurers are implementing pay-for-performance (P4P) programs in an effort to improve the quality of medical care. This article offers a paradigm for evaluating how P4P programs should be structured and how effective they are likely to be. Methods: This article assesses the current comprehensiveness of evidence-based medicine by estimating the percentage of outpatient medical spending for eighteen medical processes recommended by the Institute of Medicine. Findings: Three conditions must be in place for outcomes-based P4P programs to improve the quality of care: (1) health insurers must not fully understand what medical processes improve health (i.e., the health production function); (2) providers must know more about the health production function than insurers do; and (3) health insurers must be able to measure a patient's risk-adjusted health. Only two of these conditions currently exist. Payers appear to have incomplete knowledge of the health production function, and providers appear to know more about the health production function than payers do, but accurate methods of adjusting the risk of a patient's health status are still being developed. Conclusions: This article concludes that in three general situations, P4P will have a different impact on quality and costs and so should be structured differently. When information about patients' health and the health production function is incomplete, as is currently the case, P4P payments should be kept small, should be based on outcomes rather than processes, and should target physicians' practices and health systems. As information improves, P4P incentive payments could be increased, and P4P may become more powerful. Ironically, once information becomes complete, P4P can be replaced entirely by "optimal fee-for-service." [source] | ||||||||||||||||