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Current status of economic appraisal of health technology in the European Community: report of the network. The EC Network on the Methodology of Economic Appraisal of Health Technology.

The use of economic evaluation to assess the costs and consequences of health care technologies has steadily increased in recent years. However, little is known about the influence economic studies have on health care decision makers or policy at local and national level. This paper reports the results of a survey of economic evaluations in EC countries to identify the impact of the results on decision and policy making in health care. Health service researchers in 10 EC countries were identified and asked to participate in the survey. The researchers were asked to locate economic evaluations in their country and complete a standardised questionnaire for each study. The criteria for inclusion in the survey were first, the studies should have been started or reported since 1987, second, the evaluations should include a comparison of the cost and consequences of the technologies assessed and finally, the appraisals should include a comparison of alternative health care technologies or programmes. A total of 66 studies which met the survey criteria were reported. Of these, 27% were thought to have influenced health care decision makers or policy. The results suggested that method of dissemination, source of funding and purpose of the study may be important determinants of whether an economic evaluation will be used in health care policy or decision making. The results of the survey suggest that economic evaluation currently has a relatively low impact on health care policy or decision making.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-Benefit Analysis↗

Dynamics of autocatalytic reaction networks. IV: Inhomogeneous replicator networks.

The inhomogeneous replicator equation is derived as the continuous time model for parallel first and second order autocatalytic replication of macromolecules in a flow reactor based on mass action kinetics. It is shown that the total concentration of replicating material determines the relative importance of the first order and the second order mechanism. A complete description of the dynamics of the first order model and some special features of the inhomogeneous replicator equation are presented. A minimal prebiotic scenario with the potentiality to develop cooperation is derived from the inhomogeneous replicator equation. In this model cooperation can emerge when the total concentration of replication material exceeds a certain threshold. Below this value, a single species is selected; which one is determined by the rate constants of the first order reaction alone. Above this threshold the second order process becomes important and may lead to cooperative behavior such as hypercycles.

Biological Evolution↗

Synthesis and properties of amphiphilic networks. 1: the effect of hydration and polymer composition on the adhesion of immunoglobulin-G to poly(laurylmethacrylate-stat-glycerolmonomethacrylate-stat-ethylene-gly col-dimethacrylate) networks.

A series of hydrogels composed of varying fractions of dodecyl methacrylate (DM) and 2,3-dihydroxypropyl methacrylate (GM) were prepared using ethylene glycol dimethacrylate (EGDMA) as the cross-linking agent. The study found that for a series of gels with the same monomer ratio, bulk hydration could be controlled by adjusting the cross-link density. The ability to control cross-link density allowed the preparation of gels with the same bulk hydration but different ratios of the two monomers. The adsorption of IgG to the gels was investigated using ELISA. The aim of the project was to investigate the effect of the bulk hydration and polymer composition on IgG adsorption. The results show that for a series of gels with the same monomer ratio, there is a clear trend towards a reduction in protein adsorption as the bulk hydration and accompanying chain mobility of the gel increases. Studies on gels of the same bulk hydration but differing ratios of monomer show higher protein adsorption as the proportion of GM increases.

Adsorption↗

Social context in developmental psychopathology: recommendations for future research from the MacArthur Network on Psychopathology and Development. The MacArthur Foundation Research Network on Psychopathology and Development.

Accumulating evidence suggests that social contexts in early life have important and complex effects on childhood psychopathology. Spurred by the lack of an explicit operational definition that could guide the study of such effects, we define a social context operationally as "a set of interpersonal conditions, relevant to a particular behavior or disorder and external to, but shaped and interpreted by, the individual child." Building on this definition, we offer a series of recommendations for future research, based on five theoretically derived propositions: (a) Contexts are nested and multidimensional; (b) contexts broaden, differentiate, and deepen with age, becoming more specific in their effects; (c) contexts and children are mutually determining; (d) a context's meaning to the child determines its effects on the child and arises from the context's ability to provide for fundamental needs; and (e) contexts should be selected for assessment in light of specific questions or outcomes. As reflected in an increasingly rich legacy of literature on child development and psychopathology, social contexts appear to influence emerging mental disorders through dynamic, bidirectional interactions with individual children. Future research will benefit from examining not only statistical interactions between child- and context-specific factors, but also the actual transactions between children and contexts and the transduction of contextual influences into pathways of biological mediation. Because adverse contexts exert powerful effects on the mental health of children, it is important for the field to generate new, more theoretically grounded research addressing the contextual determinants of psychological well-being and disorder.

Child↗

A hybrid consisting of coordination polymer and noncovalent organic networks: a highly ordered 2-D phenol network assembled by edge-to-face pi-pi interactions.

A 2-D metal-organic open framework having 1-D channels, [Cu(C(10)H(26)N(6))](3)[C(6)H(3)(COO)(3)](2).18H(2)O (1), was constructed by the self-assembly of the Cu(II) complex of hexaazamacrocycle A (A = C(10)H(26)N(6)) with sodium 1,3,5-benzenetricarboxylate (BTC(3)(-)) in DMSO-H(2)O solution. 1 crystallizes in the trigonal space group P with a = b = 17.705(1) A, c = 6.940(1) A, alpha = beta = 90 degrees, gamma = 120 degrees, V = 1884.0(3) A(3), Z = 1, and rho(calcd) = 1.428 g cm(-3). The X-ray crystal structure of 1 indicates that each Cu(II) macrocyclic unit binds two BTC(3-) ions in a trans position and each BTC(3-) ion coordinates three Cu(II) macrocyclic complexes to form 2-D coordination polymer layers with honeycomb cavities (effective size 8.1 A), and the layers are packed to generate 1-D channels perpendicularly to the 2-D layers. Solid 1 binds guest molecules such as MeOH, EtOH, and PhOH with different binding constant and capacity. By the treatment of 1 with aqueous solution of phenol, a hybrid solid [Cu(C(10)H(26)N(6))](3)[C(6)H(3)(COO)(3)](2).9PhOH.6H(2)O (2) was assembled. 2 crystallizes in the trigonal R3 space group with a = b = 20.461(1) A, c = 24.159(1) A, alpha = beta = 90 degrees, gamma = 120 degrees, V = 8759.2(7) A(3), Z = 3, and rho(calcd) = 1.280 g cm(-3). In 2, highly ordered 2-D noncovalent phenol layers are formed by the edge-to-face pi-pi interactions between the phenol molecules and are alternately packed with the coordination polymer layers in the crystal lattice.

Journal Article↗

Triethanolamine zinc phosphite, (C6H13NO3)Zn2(HPO3): a templated network or a network of clusters?

(C6H13NO3)Zn2(HPO3) (I) displays an extended hybrid organic/inorganic structure in which the triethanolamine organic species acts as an anionic tetradentate ligand, rather than a typical protonated cationic template. Crystal data for I: Mr = 357.89, monoclinic, P2(1)/c (no. 14), a = 8.4216(4) angstroms, b = 9.9262(5) angstroms, c = 12.8494(6) angstroms, beta = 91.824(1) degrees, V = 1073.6(1) angstroms3, Z = 4.

Journal Article↗

Multicentric evaluation of the MDR phenotype in leukemia. French Network of the Drug Resistance Intergroup, and Drug Resistance Network of Assistance Publique-Hôpitaux de Paris.

The wide discrepancies in the frequency of 'positive' samples for multidrug resistance (MDR) phenotype within the same type of tumor observed in the literature justified the need for the definition of consensus recommendations. To define standard techniques of MDR phenotype measurement, we ran a large multicentric evaluation of the different methods available. Thirty-six French centers participated in the study, and 742 samples of 2-10 x 10(6) viable cells were sent by overnight express mail between December 1993 and February 1996. The same batches of MRK16, 4E3 and UIC2 were used. Nineteen samples of leukemia (12 AML, 1 ALL, 6 lymphoproliferative syndromes) and six leukemic cell lines with different levels of MDR expression were tested. Five meetings reached agreement concerning the guidelines for each technique, except immunocytochemistry. The 19 fresh samples were tested by each center using one to four techniques among cytofluorometry, immunocytochemistry, functional tests and RT-PCR. Five samples were diagnosed as 'negative' according to local criteria, with few discordant results (0 to 16% of 'positive' results). For all the 14 remaining samples, large discrepancies were observed from center to center, and from one technique to another. No correlations could be found between techniques. Flow cytometric analysis of cells already exposed to MRK16 or control IgG2A, fixed in paraformaldehyde and sent to centers did not reduce the discrepancies between centers in two of the four samples with moderate expression, emphasizing the role of histogram interpretation. The use of alternative monoclonal antibodies (4E3 and UIC2) did not reduce the discrepancies observed. In a second step, the K562 parental cell line, a low resistant subline (K562/HHT100, x7 resistance index to DNR) and a high resistant subline (K562/HHT300, x125 resistance index to DNR) were sent blindly three times, with an increasing level of recommendations for flow cytometry. Dramatic improvements were observed in cytometric results when the result was expressed as the ratio of arithmetic mean of fluorescence of antibody (10 microg of MRK16)/arithmetic mean of fluorescence of control (10 microg IgG2A): the proportion of expected results increased from 61 to 100% for K562, and from 37 to 85% for K562/HHT100. For uptake and drug efflux measurements, the use of 1 h uptake of 0.1 microM of rhodamine, followed by 1 h efflux +/-10 microM of verapamil, permitted an increased reproducibility of the technique from 71 to 100% for K562 and K562/HHT100. Whatever the technique used, concordant results were obtained for K562/HHT300. The immunocytochemistry, using several antibodies (MRK16, JSB1 and C219) gave many non-interpretable results (44%), due to a frequent high background and discordant results between antibodies in the same centers, and discordant conclusions between centers. The group does not recommend this technique for circulating tumoral cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

French multicentric evaluation of mdr1 gene expression by RT-PCR in leukemia and solid tumours. Standardization of RT-PCR and preliminary comparisons between RT-PCR and immunohistochemistry in solid tumours. French Network of the Drug Resistance Intergroup, and Drug Resistance Network of Assistance Publique-Hôpitaux de Paris.

Since there is no consensus on the techniques for multidrug resistance (MDR) phenotype evaluation, many discrepancies concerning the importance and frequency of mdr1 gene expression in leukemias and solid tumors are observed in the literature. In order to establish an inter-laboratory consensus in France, a multicenter study was carried out to propose further guidelines for MDR phenotype evaluation. The techniques used by the 38 laboratories participating in the trial were: immunodetection (immunohisto and/or cytochemistry, flow cytometry), functional tests, reverse transcription-polymerase chain reaction (RT-PCR) or Northern blot. We present the results obtained by 19 laboratories concerning the measurement of mdr1 gene expression assessed by RT-PCR or Northern blot in: (1)19 samples of tumor cells obtained from leukemic patients; (2) six solid tumor samples obtained at surgery; (3) eight cell lines exhibiting variable levels of resistance, and; (4)10 preparations of RNA and of cDNA obtained from solid tumors. Standardization of the RT-PCR technique and preliminary results comparing RT-PCR with immunohistochemistry in solid tumors are also reported.

ATP Binding Cassette Transporter, Subfamily B, Mem↗