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A variance-based measure of inter-rater agreement in medical databases.

The increasing use of encoded medical data requires flexible tools for data quality assessment. Existing methods are not always adequate, and this paper proposes a new metric for inter-rater agreement of aggregated diagnostic data. The metric, which is applicable in prospective as well as retrospective coding studies, quantifies the variability in the coding scheme, and the variation can be differentiated in categories and in coders. Five alternative definitions were compared in a set of simulated coding situations and in the context of mortality statistics. Two of them were more effective, and the choice between them must be made according to the situation. The metric is more powerful for larger numbers of coded cases, and Type I errors are frequent when coding situations include different numbers of cases. We also show that it is difficult to interpret the meaning of variation when the structures of the compared coding schemes differ.

Computer Simulation↗

Trends of infant mortality in Hong Kong (1956-90) and evaluation of preventable infant deaths.

OBJECTIVE: This study describes the time trends for infant mortality in Hong Kong and aims to develop statistical models that can be used to predict changes of infant mortality in places already having low levels of infant mortality. METHODOLOGY: Data on births and deaths of infants in Hong Kong during the years 1956-90 were analysed annually as well as by aggregating the data into seven consecutive quinquennia. To assess the contribution of preventable infant deaths, causes for infant deaths were classified into two broad categories: (i) congenital anomalies; and (ii) preventable diseases. A simple linear regression model was used to analyse the time trend of the mortality rate of the preventable diseases (PIMR) over the seven quinquennia. RESULTS: During the period 1956-90, the infant mortality rate fell from 60.9 in 1956-5.9 per 1000 in 1990 and the neonatal mortality rate fell from 24.2-3.8 per 1000. There was no clear time trend observed for infant mortality of congenital anomalies. However, the time trend for PIMR (log scale) was very close to a straight line and simple linear regression modelling showed a R2 of 0.9970. CONCLUSION: As the infant mortality rate (IMR) falls to below 30 per 1000, the further rate of decrease becomes less predictable from the regression model of the IMR. By removing the portion of deaths attributable to congenital anomalies, the further decrease in infant mortality became more predictable down to very low levels of IMR.

Cause of Death↗

Actin and tubulin arrays in cultured Xenopus melanophores responding to melatonin.

Melatonin induces pigment granule aggregation in amphibian melanophores. In the studies reported here, we have used fluorescence microscopic techniques to test the hypothesis that such melatonin-induced pigment movement is correlated with alterations in either the actin or tubulin cytoskeletal patterns of cultured Xenopus melanophores. In general, the cytoplasmic domains of the cultured melanophores were flat and thin except in the perinuclear region (especially when the pigment was aggregated). The microtubules and microfilaments were usually found in the same focal plane; however, on occasion, microfilaments were closer to the substratum. Microtubules were arranged in arrays radiating from what are presumed to be cytocenters. A small percentage of the melanophores were very large, had actin-rich circular perimeters and did not respond as rapidly to melatonin treatment as did the other melanophores. Melanophores with either aggregated or dispersed melanosomes had low intensity rhodamine-phalloidin staining of actin filaments compared to nonpigmented cells, whereas the FITC anti-tubulin intensities were comparable in magnitude to that seen in nonpigmented cells. When cells were fixed prior to complete melatonin-induced pigment granule aggregation there was no abrupt diminution in either the tubulin or actin staining at the boundary between pigment granule-rich and pigment granule-poor cytoplasmic domains. Nor could the actin and tubulin patterns in cells with partially aggregated melanosomes be reliably distinguished from those in melanophores in which the melanosomes were either completely dispersed or completely aggregated. These data argue against the hypothesis that melatonin causes consistent large-scale rearrangements of tubulin and actin polymers as it induces pigment aggregation in Xenopus melanophores.

Actin Cytoskeleton↗

Increased platelet aggregability associated with platelet GPIIIa PlA2 polymorphism: the Framingham Offspring Study.

The platelet glycoprotein IIb/IIIa (GP IIb/IIIa) plays a pivotal role in platelet aggregation. Recent data suggest that the PlA2 polymorphism of GPIIIa may be associated with an increased risk for cardiovascular disease. However, it is unknown if there is any association between this polymorphism and platelet reactivity. We determined GP IIIa genotype and platelet reactivity phenotype data in 1422 subjects from the Framingham Offspring Study. Genotyping was performed using PCR-based restriction fragment length polymorphism analysis. Platelet aggregability was evaluated by the Born method. The threshold concentrations of epinephrine and ADP were determined. Allele frequencies of PlA1 and PlA2 were 0.84 and 0.16, respectively. The presence of 1 or 2 PlA2 alleles was associated with increased platelet aggregability as indicated by incrementally lower threshold concentrations for epinephrine and ADP. For epinephrine, the mean concentrations were 0.9 micromol/L (0.9 to 1.0) for homozygous PlA1, 0.7 mmol/L (0.7 to 0.9) for the heterozygous PlA1/PlA2, and 0.6 micromol/L (0.4 to 1.0) for homozygous PlA2 individuals, P=0.009. The increase in aggregability induced by epinephrine remained highly significant (P=0.007) after adjustment for covariates. For ADP-induced aggregation, the respective mean concentrations were 3.1 micromol/L (3.0 to 3.2), 3.0 micromol/L (2.9 to 3.2), and 2.8 micromol/L (2.4 to 3.3); P=0.19 after adjustment for covariates. Our findings indicate that molecular variants of the gene encoding GP IIIa play a role in platelet reactivity in vitro. Our observations are compatible with and provide an explanation for the reported association of the PlA2 allotype with increased risk for cardiovascular disease.

Adenosine Diphosphate↗

Heavy Drinking and Suicide in Russia.

Russian levels of alcohol consumption and suicide are among the highest in the world. While observers have long suspected an association between the two, they were unable to investigate this hypothesis until recently due to past Soviet secrecy and thus a lack of data. This study took advantage of the newly available data during the post-Soviet era to examine the cross-sectional association between heavy drinking and suicide mortality in Russia. Aggregate mortality data for the Russian regions (n = 78) for the year 2000 were used to measure heavy drinking and suicide rates. Government data were used to control for the regional economic situation and strength of social institutions. Ordinary Least Squares regression was employed to estimate the effect of a proxy for heavy drinking on overall and sex-specific age-adjusted suicide rates. The results showed a positive and significant association between the two, and the association held for overall, male and female rates. These results not only confirmed an association between heavy drinking and suicide in Russia, but when compared to findings from previous studies of other countries they led to the hypothesis that a nation's beverage preference may be as important as its wet/dry drinking culture in its sensitivity of suicide rates to alcohol consumption.

Journal Article↗

Comparison of a quick drinking screen with the timeline followback for individuals with alcohol problems.

OBJECTIVE: Two major strategies have typically been used to assess recent drinking: (1) Daily Estimation (DE) measures such as the Timeline Followback (TLFB) and (2) Quantity-Frequency (QF) summary measures. Although QF measures provide a quick and easy measure of consumption, they have been criticized as not being able to capture sporadic and unpatterned drinking (e.g., days that reflect important social and/or health risks). The TLFB, a psychometrically sound drinking assessment method, is able to capture all drinking, including sporadic heavy days and unpatterned drinking. In some situations, however, recall of daily drinking may not be possible or practical (e.g., limited time; no resources). This article compares results obtained by using a QF measure and a DE measure to assess problem drinkers' pretreatment drinking. METHOD: The current study, part of a large community mail intervention with 825 alcohol abusers, compared results from two drinking measures covering the same time interval that were administered on two different occasions approximately 2.5 weeks apart. Both measures, the Quick Drinking Screen (QDS; a QF summary measure that collected data by telephone) and the TLFB (a self-administered daily estimation measure), collected drinking data for the year prior to the interview. RESULTS: Although the QDS and the TLFB are very different drinking measures, remarkably similar aggregate drinking data were obtained for five drinking variables. CONCLUSIONS: When it is not necessary or possible to gather detailed drinking data, the QDS produces reliable brief summary measures of drinking, at least for not severely alcohol dependent individuals. Also, respondents do not appear to use a repetitive response pattern when completing the TLFB.

Adult↗

In vivo and in vitro studies on the role of HMW-MAPs in taxol-induced microtubule bundling.

The involvement of high molecular weight microtubule-associated proteins (HMW-MAPs) in the process of taxol-induced microtubule bundling has been studied using immunofluorescence and electron microscopy. Immunofluorescence microscopy shows that HMW-MAPs are released from microtubules in granulosa cells which have been extracted in a Triton X-100 microtubule-stabilizing buffer (T-MTSB), unless the cells are pretreated with taxol. 1.0 microM taxol treatment for 48 h results in microtubule bundle formation and the retention of HMW-MAPs in these cells upon extraction with T-MTSB. Electron microscopy demonstrates that microtubules in control cytoskeletons are devoid of surface structures whereas the microtubules in taxol-treated cytoskeletons are decorated by globular particles of a mean diameter of 19.5 nm. The assembly of 3 X cycled whole microtubule protein (tubulin plus associated proteins) in vitro in the presence of 1.0 microM taxol, results in the formation of closely packed microtubules decorated with irregularly spaced globular particles, similar in size to those observed in cytoskeletons of taxol-treated granulosa cells. Microtubules assembled in vitro in the absence of taxol display prominent filamentous extensions from the microtubule surface and center-to-center spacings greater than that observed for microtubules assembled in the presence of taxol. Brain microtubule protein was purified into 6 s and HMW-MAP-enriched fractions, and the effects of taxol on the assembly and morphology of these fractions, separately or in combination, were examined. Microtubules assembled from 6 s tubulin alone or 6 s tubulin plus taxol (without HMW-MAPs) were short, free structures whereas those formed in the presence of taxol from 6 s tubulin and a HMW-MAP-enriched fraction were extensively crosslinked into aggregates. These data suggest that taxol induces microtubule bundling by stabilizing the association of HMW-MAPs with the microtubule surface which promotes lateral aggregation.

Alkaloids↗

Fusion in medical imaging: theory, interests and industrial applications.

The accumulation of several data coming from medical images and signals, expert knowledge and databases is becoming very common for the study of a given pathology. The aggregation of all this information is mentally performed by a clinician, and generally allows for a better medical decision in clinical studies. We propose in this article a fusion method that models this aggregation process. This method is a three step scheme, that first transforms all the available information in a common theoretical frame, then aggregates these data using their redundancy and their conflicts, and finally computes a new information synthesizing all the initial knowledge. We first introduce in this article the fusion scheme and its theoretical aspects, and we particularly focus on the three steps of the process. We then detail the software implementation of this concept, achieved in collaboration with SEGAMI Corporation Inc. We finally apply this concept to a real clinical problem, the study of Alzheimer's disease using MR and SPECT images, and we show very encouraging preliminary results.

Aged↗

Limitations of Health Insurance Commission (HIC) data for deriving prescribing indicators.

OBJECTIVES: To derive indicators of quality prescribing by Australian general practitioners based on Health Insurance Commission (HIC) data and assess the influence of incomplete capture of data on under-copayment drugs on the validity of these indicators. DESIGN: Two expert groups proposed prescribing indicators that can be derived from aggregate prescribing data, and which reflect important clinical or cost-effectiveness issues. Indicators were examined using HIC data and compared with national prescribing trends over time using Australian Statistics on Medicines. The effect of incomplete data capture on indicator interpretation was examined by stratifying GPs into five strata based on the proportion of concession card holders in their practice. PARTICIPANTS: Approximately 14,000 Australian GPs providing > or = 1500 Medicare services per year. MAIN OUTCOME MEASURES: Measures of prescribing for individual GPs (based on HIC data 1993-1997). RESULTS: Forty-three potentially useful indicators were identified. These covered a fairly narrow range of prescribing activities and many required additional clinical information for interpretation. Indicators based on prescribing rates gave a misleading picture of prescribing trends where the extent of HIC data capture changed over time. Indicators expressed as ratios that reflected choice of agent within a drug class were less affected by incomplete data capture. CONCLUSIONS: Indicators of quality prescribing can be derived from HIC data. However, indicators for under-copayment drugs that represent prescribing rates may unfairly classify doctors practising in areas of socioeconomic disadvantage or high morbidity as "high prescribers". Ratio indicators are more robust, and may be more valid prescribing measures. If HIC data are to be used to monitor the quality of prescribing, data on all prescriptions dispensed will be needed.

Australia↗

Quality of the family physician component of AMA Masterfile.

BACKGROUND: This investigation was undertaken to gain insight into the validity of the American Medical Association (AMA) Masterfile data. METHODS: Allopathic family physicians were chosen as the study population Omissions were picked up from by comparing the AMA list with the 1990 Ohio Academy of Family Physicians Foundation-Ohio Department of Health (OAFPF-ODH) census. Verification of the 1990 specialty and geographic location of allopathic family physicians not common to both files was achieved by sequentially (1) reviewing the AMA names against 1990 deletions from the 1985 OAFPF-ODH census, (2) contacting physicians directly by telephone, (3) verifying 1990 physician status with county medical personnel, and (4) mailing a brief questionnaire to each physician whose 1990 status remained unverified. RESULTS: The status of specialty and geographic location in 1990 was verified in 91 percent of names not common to both lists. Incorrect omissions (undercounts) and incorrect inclusions (overcounts) offset each other for both lists. Two groups of family physicians contribute to counting biases: family physicians who fulfill short-term goals by part-time practice in several locations, and family physicians who restrict their practice to a limited medical content area. CONCLUSIONS: Because of nearly equal offsetting of overcounting (incorrect inclusions) and under counting (incorrect omissions), the 1990 Ohio family physician AMA Masterfile data is adequate for work-force projections and policy studies when the county data are aggregated at the state level. The overcounting and undercounting for smaller areas or categories must still be studied, however. Application of the AMA Masterfile data of other geographic areas requires a knowledge of the components of undercounts and overcounts of the population being studied.

American Medical Association↗

Platelet-activating factor and macrophages. I. Evidence for the release from rat and mouse peritoneal macrophages and not from mastocytes.

Platelet-activating factor (PAF) is a phospholipid mediator of anaphylaxis, released from basophils of several mammalian species, that aggregates platelets and releases their vasoactive amines. The ionophore A23 187 induced the release of PAF from rat and mouse peritoneal cells, a mixed cell population that was fractionated using 5--15% Ficoll gradients and adherence to plastic petri dishes. PAF was associated with large, acid phosphatase-containing, adherent mononuclear cells. Mastocytes did not release PAF but released histamine by the action of ionophore or 48/80; they could not be held responsible for inactivation of PAF or inhibition of the PAF-induced platelet aggregation. These data indicate that, besides blood basophils, peritoneal macrophages are a likely source for PAF, a result that adds a new important function to the macrophage:aggregation of platelets and liberation of their inflammatory and vasoactive substances.

Animals↗

Compressive stress-relaxation behavior of bovine growth plate may be described by the nonlinear biphasic theory.

The compressive behavior of the bovine distal femoral growth plate was studied in vitro. Strain-rate controlled, compression stress-relaxation experiments were performed on cylindrical bone-growth plate-bone specimens from the interior and periphery of the growth plate. The questions addressed in this study were (a) Can the nonlinear biphasic theory, one with strain-dependent permeability, be used to represent the compressive stress-relaxation behavior of bovine growth plate? (b) How do different assumptions concerning the permeabilities of the chondro-osseous interfaces influence the inferred material properties of the growth plate? and (c) Are there any differences in these properties between the periphery and the interior of the growth plate? Intrinsic biphasic material properties--aggregate modulus (HA), Poisson's ratio (v), and nonlinear strain-dependent permeability coefficients (ko and M)--were calculated from the compression stress-relaxation data with use of a finite element model and a least squares curve-fitting procedure. To verify this constitutive model for the growth plate, an independent set of finite element analyses was performed with use of the determined intrinsic biphasic properties, and comparisons were made between these finite element predictions and two additional sets of experimental data subsequently obtained for the same specimens with use of two slower rates of compression. Excellent agreement was achieved between these finite element predictions and the latter two sets of data. The aggregate modulus was found to be insensitive to the permeability of the chondro-osseous interface. The permeability coefficients were very sensitive to, and the Poisson's ratio was only slightly sensitive to the interface permeability condition. Therefore, the periphery of the growth plate is more compliant and permeable than the interior.

Animals↗

Pharmacotherapy for allergic rhinitis: a critical review of leukotriene receptor antagonists compared with other treatments.

OBJECTIVE: To review the mechanisms and clinical efficacy of leukotriene receptor antagonists, which are investigational therapies for allergic rhinitis, compared with intranasal corticosteroids and nonsedating antihistamines, which are the most commonly prescribed pharmacotherapies for allergic rhinitis. DATA SOURCES: Computer-assisted MEDLINE searches for articles and manual searches of conference proceedings on intranasal corticosteroid, antihistamine, leukotriene receptor antagonist, leukotriene modifier, zafirlukast, montelukast, allergic rhinitis, rhinitis, and asthma. SELECTION: Published articles and pertinent abstracts on the topics identified above were selected. Head-to-head comparator trials as well as data from placebo-controlled trials were selected. RESULTS AND CONCLUSIONS: The studies published to date demonstrate that leukotriene receptor antagonists are sometimes more effective than placebo, are no more effective than nonsedating antihistamines, and are less effective than intranasal corticosteroids in the treatment of allergic rhinitis. The combination of a leukotriene receptor antagonist and an antihistamine has not been proven to be more effective than either agent alone. This review reveals several inconsistencies that require resolution. First, whereas leukotriene receptor antagonists are predicted on the basis of their mechanism of action to improve nasal congestion significantly, clinical studies reveal leukotriene receptor antagonists to be no better than antihistamines at improving congestion. Second, leukotriene receptor antagonists would not be expected on the basis of their putative mechanism of action or nasal challenge data to improve significantly sneezing, nasal itching, or drainage. However, some studies show improvement in these symptoms during treatment with leukotriene receptor antagonists. Considered in aggregate, the data available to date do not clearly support a unique role of leukotriene receptor antagonists in the treatment of allergic rhinitis whether or not it is accompanied by asthma.

Adrenal Cortex Hormones↗

Using Medicaid claims to construct dental service market areas.

OBJECTIVE: To use Medicaid claims data to construct patient origin-based market areas for dental services and compare constructed market areas with those based on the practice county. DATA SOURCES: North Carolina Medicaid claims, eligibility, and provider files, the Cooperative Health Information Systems' dentist licensure files, and the Log Into North Carolina data. STUDY DESIGN: A visit-level file was created from the Medicaid claims data and aggregated by provider practice county and patient county of residence. Using the aggregated file and an algorithm based on the Elzinga-Hogarty approach, patient travel patterns were used to construct mutually exclusive patient origin market areas. DATA ANALYSIS: Market area characteristics were compared across definitions using Pearson correlation coefficients. In addition, estimations of provider participation were performed using market area characteristics as control variables. The beta coefficients associated with market area characteristics were compared across market area definitions. PRINCIPAL FINDINGS: Medicaid claims data, when combined with provider licensure files, can be used to construct market areas based on patient origin data. However, measures of market area characteristics are correlated highly between the two types of market areas studied. Furthermore, beta coefficients on market area variables in models of provider participation are similar in sign, significance, and magnitude across market definitions. CONCLUSIONS: Compared with market areas constructed using patient origin data, county-based market areas adequately proxy for dental markets. Using the county as the market area also avoids the time and computational costs associated with using a patient origin-based approach and facilitates the use of widely available data.

Catchment Area, Health↗

Community Hospital-based Stroke Programs: North Carolina, Oregon, and New York. I: Goals, objectives, and data collection procedures.

In order to assess the impact of variations in stroke care on outcomes, and to make geographic comparisons, the three Community Hospital-Based Stroke Programs in North Carolina, Oregon, and New York, aggregated their data on 4,132 hospitalized stroke patients. Complete demographic data or "Major Profile" were obtained on 2,390 (57.8%) of the 4,132 stroke patients. This includes those patients on whom informed patient and physician consents were obtained during the hospitalization. Of the major profile patients, 1,490 (62.3%) were followed for periods up to one year, 502 (21.0%) were lost to followup and 398 (16.6%) died within the one year followup period. Incomplete demographic data or "Minor Profile" were observed on 1,742 (42.1%) of the 4,132 patients. Minor profile includes those who died before comprehensive interviews were completed or those for whom informed consent for an interview could not be obtained. Of the minor profile group, 813 (46.7%) died in hospital, and 929 (53.3%) were alive when discharged from the hospital. This paper, which describes the programs, data collection procedures, and study cases, also highlights specific issues on stroke diagnosis, risk factors associated with stroke, and the influence of interventions on stroke outcomes. We conclude that: 1) the merging of data on hospitalized stroke cases from rural and urban hospitals in geographically distinct regions can be used in the study of stroke diagnosis, the use of diagnostic tests, and the effect of interventions on stroke outcomes; and 2) these data are consistent with the hypothesis that part of the national decline in mortality from stroke is due to a decline in stroke severity.

Adult↗

Studies on vitiligo. II. Familial aggregation and genetics.

Data on 298 pedigrees, each collected through an affected proband, have been analyzed to study familial aggregation and genetics of vitiligo. The extent of familial aggregation is statistically significant at the 5% level. The disease does not appear to be inherited in a simple dominant or recessive fashion. The heritability of liability to the disease is 46% +/- 4.82%. Neither common family environment nor a major locus with additional sources (environmental and/or polygenic) can be excluded as a cause of familial aggregation. Association of the disease with six polymorphic genetic marker loci have been studied. Significant associations with ACP1 and RH loci have been found. This and earlier studies indicate that the disease is associated with genetic loci on different chromosomes, which points to a polygenic nature of the disease.

Acid Phosphatase↗

Why are eligible patients not prescribed aspirin in primary care? A qualitative study indicating measures for improvement.

BACKGROUND: Despite evidence-based guidelines, aspirin prescribing for the secondary prevention of stroke is sub-optimal. Little is known about why general practitioners do not prescribe aspirin to indicated patients. We sought to identify and describe factors that lead general practitioners (GPs) not to prescribe aspirin to eligible stroke patients. This was the first stage of a study exploring the need for and means of improving levels of appropriate aspirin prescribing. METHOD: Qualitative interviews with 15 GPs in the West Midlands. RESULTS: Initially, many GPs did not regard their prescribing as difficult or sub-optimal. However on reflection, they gave several reasons that lead to them not prescribing aspirin for eligible patients or being uncertain. These include: difficulties in applying generic guidelines to individuals presenting in consultations, patient resistance to taking aspirin, the prioritisation of other issues in a time constrained consultation and problems in reviewing the medication of existing stroke patients. CONCLUSION: In order to improve levels of appropriate aspirin prescribing, the nature and presentation risk information available to GPs and patients must be improved. GPs need support in assessing the risks and benefits of prescribing for patients with combinations of complicating risk factors, while means of facilitating improved GP-patient dialogue are required to help address patient uncertainty. A decision analysis based support system is one option. Decision analysis could synthesise current evidence and identify risk data for a range of patient profiles commonly presenting in primary care. These data could then be incorporated into a user-friendly computerised decision support system to help facilitate improved GP-patient communication. Measures of optimum prescribing based upon aggregated prescribing data must be interpreted with caution. It is not possible to assess whether low levels of prescribing reflect appropriate or inappropriate use of aspirin in specific patients where concordance between the GP and the patient is practised.

Aspirin↗

A small hydrophobic domain that localizes human erythrocyte acetylcholinesterase in liposomal membranes is cleaved by papain digestion.

A small hydrophobic domain in isolated human erythrocyte acetylcholinesterase is responsible for the interaction of this enzyme with detergent micelles and the aggregation of the enzyme on removal of detergent. Papain has been shown to cleave this hydrophobic domain and to generate a fully active hydrophilic enzyme that shows no tendency to interact with detergents or to aggregate [Dutta-Choudhury, T.A., & Rosenberry, T.L. (1984) J. Biol. Chem. 259, 5653-5660]. We report here that the intact enzyme could be reconstituted into phospholipid liposomes while the papain-disaggregated enzyme showed no capacity for reconstitution. More than 80% of the enzyme reconstituted into small liposomes could be released by papain digestion as the hydrophilic form. Papain was less effective in releasing the enzyme from large liposomes that were probably multilamellar. In a novel application of affinity chromatography on acridinium resin, enzyme reconstituted into small liposomes in the presence of excess phospholipid was purified to a level of 1 enzyme molecule per 4000 phospholipid molecules, a ratio expected if each enzyme molecule was associated with a small, unilamellar liposome. Subunits in the hydrophilic enzyme form released from reconstituted liposomes by papain digestion showed a mass decrease of about 2 kilodaltons relative to the intact subunits according to acrylamide gel electrophoresis in sodium dodecyl sulfate, a difference similar to that observed previously following papain digestion of the soluble enzyme aggregates. The data were consistent with the hypothesis that the same hydrophobic domain in the enzyme is responsible for the interaction of the enzyme with detergent micelles, the aggregation of the enzyme in the absence of detergent, and the incorporation of the enzyme into reconstituted phospholipid membranes.

Acetylcholinesterase↗