Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Rationalization”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 667 records · Page 37Linked to original sources
PubMed1998

Atopic eczema between rationality and irrationality.

A topic eczema is one of the most common chronic inflammatory skin diseases. Its treatment is a matter of intensive controversy between rational academic medicine and irrational alternative complementary medicine more than any other skin disease. Rational therapy is based on a sound pathophysiological foundation. The complex pathophysiology of the disease includes interactions between genetic predisposition and exogenous provocation factors, and treatment necessitates an integrated holistic approach. Despite excellent therapeutic results with the methods of conventional medicine, which uses mostly drugs of natural origin such as glucocorticosteroids, patients with atopic eczema and their parents frequently seek complementary treatments that use unproven and unvalidated diagnostic and therapeutic procedures. Treatments based on simplistic theories and irrational ideologies cause unnecessary long-term suffering to patients and are harmful because they withhold effective treatment modalities.

Combined Modality Therapy↗
PubMed1985

Pediatric health rationing. Recent trends and lessons from history.

Recent health care rationing proposals are related to shifting economic and political priorities. Pediatric implications of these proposals include restrictive policies toward premature and congenitally malformed newborns. Historical experience of similar developments suggests that early warning signals of such measures should be heeded to avoid major public health consequences. In the best interests of society-at-large, health care rationing should be rejected.

Abnormalities, Multiple↗
PubMed1999

Rational decision-making in mental health: the role of systematic reviews.

BACKGROUND: "Systematic reviews" have come to be recognized as the most rigorous method of summarizing confusing and often contradictory primary research in a transparent and reproducible manner. Their greatest impact has been in the summarization of epidemiological literature - particularly that relating to clinical effectiveness. Systematic reviews also have a potential to inform rational decision-making in healthcare policy and to form a component of economic evaluation. AIMS OF THE STUDY: This article aims to introduce the rationale behind systematic reviews and, using examples from mental health, to introduce the strengths and limitations of systematic reviews, particularly in informing mental health policy and economic evaluation. METHODS: Examples are selected from recent controversies surrounding the introduction of new psychiatric drugs (anti-depressants and anti-schizophrenia drugs) and methods of delivering psychiatric care in the community (case management and assertive community treatment). The potential for systematic reviews to (i) produce best estimates of clinical efficacy and effectiveness, (ii) aid economic evaluation and policy decision-making and (iii) highlight gaps in the primary research knowledge base are discussed. Lastly examples are selected from outside mental health to show how systematic reviews have a potential to be explicitly used in economic and health policy evaluation. RESULTS: Systematic reviews produce the best estimates of clinical efficacy, which can form an important component of economic evaluation. Importantly, serious methodological flaws and areas of uncertainty in the primary research literature are identified within an explicit framework. Summary indices of clinical effectiveness can be produced, but it is difficult to produce such summary indices of cost effectiveness by pooling economic data from primary studies. Modelling is commonly used in economic and policy evaluation. Here, systematic reviews can provide the best estimates of effectiveness and, importantly, highlight areas of uncertainty that can be used in "sensitivity analysis". DISCUSSION: Systematic reviews are an important recent methodological advance, the potential for which has only begun to be realized in mental health. This use of systematic reviews is probably most advanced in producing critical summaries of clinical effectiveness data. Systematic reviews cannot produce valid and believable conclusions when the primary research literature is of poor quality. An important function of systematic reviews will be in highlighting this poor quality research which is of little use in mental health decision making. IMPLICATIONS FOR HEALTH PROVISION: Health care provision should be both clinically and cost effective. Systematic reviews are a key component in ensuring that this goal is achieved. IMPLICATIONS FOR HEALTH POLICIES: Systematic reviews have potential to inform health policy. Examples presented show that health policy is often made without due consideration of the research evidence. Systematic reviews can provide robust and believable answers, which can help inform rational decision-making. Importantly, systematic reviews can highlight the need for important primary research and can inform the design of this research such that it provides answers that will help in forming healthcare policy. IMPLICATIONS FOR FURTHER RESEARCH: Systematic reviews should precede costly (and often unnecessary) primary research. Many areas of health policy and practice have yet to be evaluated using systematic review methodology. Methods for the summarization of economic data are methodologically complex and deserve further research

Journal Article↗
PubMed2000

Rational basis for Trk inhibition therapy for prostate cancer.

BACKGROUND: Prostatic cancer cells are lethal because they acquire the ability to activate survival pathways that do not require androgenic stimulation. As a rational approach to developing effective therapy for these devastating cells, specific signal transduction pathways uniquely required for the survival of these nonandrogen-dependent prostate cancer cells must be identified. Previous studies suggested that the neurotrophin/trk signal transduction axis may regulate such unique survival pathways. In the present study, the changes in expression of the neurotrophins (NGF, BDNF, and NT-3) and their cognate receptors (i.e., trk and p75NTR) during the progression of normal prostatic epithelial cells to malignancy were documented. Additionally, the consequences of inhibiting these trk signaling pathways on the in vitro survival of prostate cancer cells was tested. METHODS: Immmunocytochemistry, RT-PCR, and ELISA assays were used to characterize the changes in the neurotrophin ligands (i.e., NGF, BDNF, and NT-3) and their cognate high-affinity (i.e., trk A, B, and C) and low-affinity neurotrophin (i.e., p75 NTR) receptors in normal vs. malignant human prostatic tissues. CEP-751 is an indolocarbazole compound specifically designed to inhibit the initiation of these neurotrophin/trk signal transductions. The consequence of CEP-751 inhibition of trk signaling for in vitro clonogenic survival of a series of human prostatic cancer lines was also tested. RESULTS: These studies demonstrated that normal prostatic tissue from patients without prostate cancer contains substantial levels of nerve growth factor (NGF), which is produced in a paracrine manner by stromal cells. These stromal cells lack both trk and p75NTR receptors. In contrast, normal prostatic epithelial cells from patients without prostate cancer do not secrete detectable levels of neurotrophins, but do express trk A and p75 NTR. While the NGF/trkA/p75 NTR axis is present in the normal prostate, normal prostatic epithelial cells do not depend on this axis for their survival. In contrast, malignant prostate epithelial cells directly secrete a series of neurotrophins (i.e., NGF, BDNF, and/or NT-3) and express at least one if not more of the trk receptor proteins (i.e., trk A, B, and/or C), while no longer expressing the p75NTR receptors. In addition, inhibition of autocrine trk signaling via CEP-751 treatment induces the apoptotic death of these malignant cells. CONCLUSIONS: Prostate carcinogenesis involves molecular changes leading to the paracrine and/or autocrine production of a series of neurotrophins. This is coupled to the ectopic expression of trk B and trk C, as well as to the continued expression of trk A, and the loss of expression of p75NTR receptors. These changes result in the acquisition by malignant prostate cells of a unique requirement for trk signaling pathways for survival. Based on these findings, trk inhibition is a novel, rational approach for prostate cancer therapy.

Animals↗
PubMed2000

Interpreting the rational addiction model.

The rational addiction (RA) model of Becker and Murphy (Becker GS, Murphy KM. A theory of rational addiction. J Pol Econ 1988; 96(4): 675-700) has rapidly become one of the standard models in the literature on addictive behaviour. This paper reviews some theoretical issues surrounding its use, and indicates areas in which caution should be used in applying this model.

Behavior, Addictive↗
PubMed2002

Inorganic semiconductor nanowires: rational growth, assembly, and novel properties.

Rationally controlled growth of inorganic semiconductor nanowires is important for their applications in nanoscale electronics and photonics. In this article, we discuss the rational growth, physical properties, and integration of nanowires based on the results from the authors' laboratory. The composition, diameter, growth position, and orientation of the nanowires are controlled based on the vapor-solid-liquid (VLS) crystal growth mechanism. The thermal stability and optical properties of these semiconductor nanowires are investigated. Particularly, ZnO nanowires with well-defined end surfaces can function as room-temperature ultraviolet nanolasers. In addition, a novel microfluidic-assisted nanowire integration (MANI) process was developed for the hierarchical assembly of nanowire building blocks into functional devices and systems.

Journal Article↗
PubMed2002

Towards rational syntheses of the elusive metallocarbohedrenes: density functional prescriptions for electronic and geometric structures.

The metallocarbohedrenes are binary molecular clusters containing metal atoms linked by acetylenediide C(2) groups. Hundreds of these molecules have been generated, detected and reacted in the gas phase since the prototype, [Ti(8)(C(2))(6)], was reported in 1992, but none has yet been synthesised pure in bulk: the time gap between detection and preparation increasingly exceeds that of the fullerenes. We report here the results of density functional calculations of geometrical and electronic structure of more than 150 postulated metallocarbohedrenes, stabilised by terminal ligation, in order to recognise the more electronically favourable and less reactive targets. At least 38 metallocarbohedrenes have been identified as having a spin singlet ground state, with a relatively large (> 0.5 eV) energy gap between HOMO and LUMO, and an appropriate HOMO energy. In addition, a considerable number of electronically stable metallocarbohedrenes are predicted to have highly paramagnetic ground states, potentially useful in molecular magnetism. The geometrical principles for enclosing but unstrained coordination of metal sites by terminal ligands are outlined. Mechanisms for rational syntheses are considered in the context of reaction type and precursor selection, including issues of oxidation and reduction, and kinetic versus thermodynamic control. This leads to many diverse reactions suggested for the rational syntheses of metallocarbohedrenes. Some preliminary experimental results are presented.

Journal Article↗
PubMed2002

Rationally designed fluorescently labeled sulfate-binding protein mutants: evaluation in the development of a sensing system for sulfate.

Periplasmic binding proteins from E. coli undergo large conformational changes upon binding their respective ligands. By attaching a fluorescent probe at rationally selected unique sites on the protein, these conformational changes in the protein can be monitored by measuring the changes in fluorescence intensity of the probe which allow the development of reagentless sensing systems for their corresponding ligands. In this work, we evaluated several sites on bacterial periplasmic sulfate-binding protein (SBP) for attachment of a fluorescent probe and rationally designed a reagentless sensing system for sulfate. Eight different mutants of SBP were prepared by employing the polymerase chain reaction (PCR) to introduce a unique cysteine residue at a specific location on the protein. The sites Gly55, Ser90, Ser129, Ala140, Leu145, Ser171, Val181, and Gly186 were chosen for mutagenesis by studying the three-dimensional X-ray crystal structure of SBP. An environment-sensitive fluorescent probe (MDCC) was then attached site-specifically to the protein through the sulfhydryl group of the unique cysteine residue introduced. Each fluorescent probe-conjugated SBP mutant was characterized in terms of its fluorescence properties and Ser171 was determined to be the best site for the attachment of the fluorescent probe that would allow for the development of a reagentless sensing system for sulfate. Three different environment-sensitive fluorescent probes (1,5-IAEDANS, MDCC, and acylodan) were studied with the SBP171 mutant protein. A calibration curve for sulfate was constructed using the labeled protein and relating the change in the fluorescence intensity with the amount of sulfate present in the sample. The detection limit for sulfate was found to be in the submicromolar range using this system. The selectivity of the sensing system was demonstrated by evaluating its response to other anions. A fast and selective sensing system with detection limits for sulfate in the submicromolar range was developed.

Bacterial Proteins↗
PubMed2003

Competency to stand trial: rationalism, "contextualism" and other modest theories.

Determinations of competency to stand trial in criminal cases are complicated and rendered unpredictable by two sub-surface issues that are rarely articulated: (i) the place of the defendant's rationality in the substantive standard(s) for competency and (ii) the level or degree of incompetency required to stop the criminal process. The rare references to these issues, mostly indirect, that are made in the cases, commentary, and competency testing instruments devised (including those civil as well as criminal) are examined. The conclusion that emerges is that the level of capacity and rationality required of the defendant depends much on context-the type of case, its relative complexity, and the values and stakes implicated in the outcome.

Crime↗
PubMed2003

Rational chemical strategies for carbon nanotube functionalization.

Whereas the chemistry of fullerenes is well-established, the chemistry of single-walled carbon nanotubes (SWNTs) is a relatively unexplored field of research. Investigations into the bonding of moieties onto SWNTs are important because they provide fundamental structural insight into how nanoscale interactions occur. Hence, understanding SWNT chemistry becomes critical to rational, predictive manipulation of their properties. Among the strategies discussed include molecular metal complexation with SWNTs to control site-selective chemistry in these systems. In particular, work has been performed with Vaska's and Wilkinson's complexes to create functionalized adducts. Functionalization should offer a relatively simple means of tube solubilization and bundle exfoliation, and also allows for tubes to be utilized as recoverable catalyst supports. Solubilization of oxidized SWNTs has also been achieved through derivatization by using a functionalized organic crown ether. The resultant adduct yielded concentrations of dissolved nanotubes on the order of 1 g L(-1) in water and at elevated concentrations in a range of organic solvents, traditionally poor for SWNT manipulation. To further demonstrate chemical processability of SWNTs, we have subjected them to ozonolysis, followed by treatment with various independent reagents, to rationally generate a higher proportion of oxygenated functional groups on the nanotube surface. This protocol has been found to purify nanotubes. More importantly, the reaction sequence has been found to ozonize the sidewalls of these nanotubes. Finally, SWNTs have also been chemically modified with quantum dots and oxide nanocrystals. A composite heterostructure consisting of nanotubes joined to nanocrystals offers a unique opportunity to obtain desired physical, electronic, and chemical properties by adjusting synthetic conditions to tailor the size and structure of the individual sub-components, with implications for self-assembly.

Journal Article↗
PubMed1990

[The effect of energy-rich and energy-reduced rations with n-alkane yeast portions on the fatty acid composition of selected organ lipids in swine].

In 3 test groups (11 pigs in each group) rations with identical fatty acid patterns (except C 17 acids) at high, medium and low-energy levels of the rations were fed. The fatty acid composition of the lipids of liver, heart and brain was analyzed at the end of the experiments. A correlation was found to exist between energy and fatty acid intake and the fatty acid spectrum of the organ lipids. With identical intake of odd-numbered fatty acids, an energy-rich diet leads to a reduction of odd-numbered fatty acids in the heart and liver lipids. A reduced energy concentration causes an increase of odd-numbered fatty acids in liver and heart. Under energy-rich and energy-reduced feeding, C 15 and C 19 acids can be traced in the hepatic lipids. In liver, heart and brain, an energy-rich diet results in increased contents of eicosapentaene and eicosahexaene acid. Under low-energy diet, a reduction of these fatty acids can be found in the brain.

Animal Feed↗
PubMed2006

Rational alcohol addiction: evidence from the Russian longitudinal monitoring survey.

Alcohol consumption in Russia is legendary and has been reported to be the third leading cause of death in the former Soviet Union after heart disease and cancer. Are Russian alcohol consumers rational addicts? This paper uses eight rounds of a nationally representative Russian survey spanning the period 1994-2003 to estimate a rational addiction (RA) model for alcohol consumption. This is done in a panel data setting as well as on a wave-by-wave basis. The profile of the Russian drinker finds a huge difference between males and females and the model is estimated by gender. We do not find support for the RA model in Russia for women. For men, although we find that some implications of the RA model are satisfied, we fail to endorse the model empirically on grounds of implausible negative estimates of the discount rate.

Adolescent↗
PubMed2002

Rational addiction to alcohol: panel data analysis of liquor consumption.

Utilizing a panel data set of 42 states over the period 1959-1994, this paper estimates a rational addiction model for liquor consumption for the US. The empirical evidence is consistent with the rational addiction hypothesis proposed by Becker and Murphy. However, the results are sensitive to the assumption of homogeneity across states or over time.

Adult↗
PubMed2006

Rational use of drugs: prescribing and dispensing practices at public health facilities in Lao PDR.

PURPOSE: To evaluate the rational use of drug (RUD) patterns with a focus on prescribing and dispensing practices for providing information to the policy makers for further planning and identifying intervention strategies. METHOD: A cross-sectional study conducted by interviewing 370 presenting outpatients, checking records of 900 out- patients with any cases and 798 outpatients with tracer diseases such as simple diarrhea, pneumonia and non-pneumonia (Flu) within 30 public health facilities (HFs) of five geographical areas with different socio-economic statuses grouped into high, middle and low. The WHO Operational Package for Monitoring and Assessing Country Pharmaceutical Situations indicators were used for data collection. RESULTS: Among the 3 items of drugs prescribed per average encounter, 97% were dispensed from HFs, of which 67% were adequately labeled, 84% were on the national essential drug (ED) list, and 78% were prescribed by generic name. Seventy-four percent of patients knew how to take the drugs they received, 47% of them received antibiotics (ABs), and 18% received injections. Forty-seven percent of under-five children with simple diarrhea received ABs, 77% received Oral Rehydration Salts (ORS) and 5% received anti-diarrhea drugs, and 91% of such under-five children with mid/moderate pneumonia received one of first line ABs, 15% received more than one ABs, and 41% of non-pneumonia (flu) patients of any age received ABs. CONCLUSION: The use of drugs in Laos was not fully appropriate in terms of rationally prescribing and dispensing practices. Since prescriptions for AB, injections, non-ED, and non-generics are still high, information on drug use provided is insufficient. Therefore, continuous health education programs among both health staff and public are needed.

Cross-Sectional Studies↗
PubMed1995

Elucidating the folding problem of helical peptides using empirical parameters. II. Helix macrodipole effects and rational modification of the helical content of natural peptides.

Explaining the helical behaviour of amino acid sequences in solution could be one of the first steps in solving the protein folding problem in a rational way. The information about the conformational behaviour of helical peptides in solution, as well as the alpha-helix stability in proteins, has been utilised to derive a database with the energy contributions for various interaction taking place in an alpha-helix: intrinsic helical propensities, side-chain to side-chain interactions, main-chain to main-chain hydrogen bonds, and capping effects. This database was implemented in a algorithm based on the helix-coil transition theory (AGADIR). Here, the effects on helix stability due to interactions between charged groups and the helix macrodipole are described, quantified and implemented in AGADIR. The algorithm correctly calculates the average helical behaviour in solution of 423 peptides analysed by circular dichroism and it describes the helicity at a residue level, as found when comparing the prediction for each amino acid residue with the data derived from nuclear magnetic resonance studies. Using AGADIR we have done a rational modification of peptides corresponding to protein secondary structure elements in order to increase their helical content. The circular dichroism analysis of the mutant peptides showed a very good agreement between the experimental and calculated helical content. Moreover, in certain specific cases in which strong tertiary contacts in folded proteins do not exist, the algorithm successfully predicts the length of mutagenised alpha-helices. It is interesting to note that the final values of the parameters used do not significantly differ in absolute terms from those extracted from mutagenesis studies in proteins. This indicates that the same physico-chemical principles stand for both systems.

Algorithms↗
PubMed1996

Rational design of receptor partial agonists and possible mechanisms of receptor partial activation: a theory.

Partial activation of membrane receptors using specific partial agonists may be particularly beneficial to the treatment of some chronic diseases like congestive heart failure, because receptor partial activation usually avoids overstimulation and also minimizes desensitization. At present, partial agonists are obtained almost exclusively by screening numerous newly-synthesized compounds, and little is known about the rational design of partial agonists with desired potencies and maximum activities. It is proposed in this study that a proper covalent attachment of a receptor full agonist to an antagonist (competitive or non-competitive) of the same receptor type may form a hybrid compound with a reduced maximum activity. In theory, the potency (EC50 value) and the reduced maximum activity of such an agonist-antagonist hybrid are predictable, based on the receptor binding affinities of the incorporated agonist and antagonist. The agonist-noncompetitive antagonist hybrids produce bell-shaped concentration-response curves, whereas the agonist-competitive antagonist hybrids produce concentration-response curves with reduced but plateaued maximum responses. The agonist-competitive antagonist hybrids can be very useful for therapeutic purposes because they enable us to stably activate a specific type of receptor at desired submaximal set-points. In this study, it is postulated that some partial agonists may also contain both agonistic and antagonistic moieties, analogous to the proposed hybrid compounds. This hypothesis is supported by data from modeling studies showing that several unique pharmacological characteristics of known partial agonists exactly match the projected features of the agonist-antagonist hybrid compounds. Modeling studies based on the hybrid compound model also explain why the reduced maximum response elicited by some partial agonists can be increased or even fully restored in the presence of spare receptors. As indicated by modeling studies, a reduced maximum activation of receptors may, at least in some cases, not result from a partial activation of each individual receptor being occupied by the partial agonist, but rather may be due to a reduced maximal receptor occupancy by the agonistic moiety in the co-presence of an antagonistic moiety. The agonist-antagonist hybrid proposed in this study not only enhances our understanding of the possible structural requirements and rational design of receptor partial agonists, but it also enhances our understanding of the possible molecular basis of receptor partial activation. This new model also provides an alternative mathematical framework for modeling partial agonist data.

Binding, Competitive↗
PubMed1994

Juvenile hormone esterase purified by affinity chromatography with 8-mercapto-1,1,1-trifluoro-2-octanone as a rationally designed ligand.

Trifluoromethyl ketones are potent inhibitors of a variety of serine hydrolases. Based on this chemistry improved affinity chromatography procedures were developed for juvenile hormone esterase from insects. New affinity gels were prepared by binding rationally designed ligands to epoxy-activated Sepharose. One ligand is 8-mercapto-1,1,1-trifluoro-2-octanone which has a methylene group replacing a sulfide sulfur beta to the carbonyl of the trifluoromethyl ketone of the previously reported ligand, 3-(4-mercaptobutylthio)-1,1,1-trifluoro-2-propanone. With many loading levels and esterases, the original gel bound enzymes too tightly, resulting in elution difficulties. This replacement of the sulfur beta to the ketone thought to interact with the catalytic serine decreases the binding capacity of the gel at similar loading by approximately 56% compared to the affinity gel with the thioether. However, elution of the enzyme from the column can be accomplished with less potent inhibitors such as 3-n-butylthio- or 3-n-pentylthio-1,1,1-trifluoro-2-propanone, which can easily be removed from the enzyme by dialysis in the presence of the detergent n-octyl beta-D-glucopyranoside. An alternative approach allowing elution with less potent inhibitors involved varying concentrations of the previous high-affinity ligand to optimize the concentration of ligand on the column. Low concentrations of the high-affinity ligand also allowed the use of less potent eluting agents. These two improved affinity chromatography systems have been successfully used to purify juvenile hormone esterase of Heliothis virescens to near homogeneity with a 30-90% recovery of recombinant esterase secreted into the cell media in a baculovirus expression system. The purity of the esterase after affinity chromatography with newly prepared gel was comparable to that produced using the original affinity system based on analyses by SDS-PAGE and isoelectric focusing. A library of affinity gels with ligands of different affinities used at several loading levels and a library of eluting inhibitors of varying potency facilitate the rational selection of conditions for the affinity purification of esterases.

Animals↗
PubMed1987

Study of osteogenesis in adult sheep on a high and a low calcium ration by means of fluorescing bone markers.

The rate of osteogenesis was studied in 8 non-pregnant, non-lactating Friesian dairy sheep, 3-6 years old, by means of a treatment with 3 different bone seeking agents. Four sheep were fed a low calcium ration (LCa:1.8 g Ca/d) and four other sheep a high calcium ration (HCa:12.7 g Ca/d). The bone markers, oxytetracycline-HCl, alizarine-complexion and demeclocycline-HCl, were administered at intervals of 6 weeks, and the sheep were killed 1 week after administration of the last marker. In undecalcified cross sections from the middle of ribs 2, 10 and 12, and from the proximal and distal parts of rib 10, the numbers of labelled osteons and the number of osteons with 1, 2 or 3 markers were counted under fluorescent microscopy. In the ribs of sheep from the LCa group, the number of labelled osteons and the quantity of labels per osteon tended to be higher than those of sheep from the HCa group. When osteogenic activity was compared in the different sites of ribs analysed, lowest osteogenic activity was observed in the proximal part of the 10th rib. The use of fluorescing markers offers the possibility of studying osteogenic activity over a certain period of time in adult sheep.

Animals↗