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Profiles of respite use.

Profiles of long-term respite use are reported for a diverse sample of 4,369 families from seven states who participated in the Alzheimer's Disease Demonstration Grant to States program. Data from service records spanning a period of seven years were analyzed using hierarchical linear modeling techniques. Respite use was examined in both day care and in-home settings using three different measures of use. Client characteristics related to use include the caregiver's gender and relationship to the elder, and the ethnicity, income, functional level, and problem behaviors of the elder. Provider characteristics linked with different patterns of use include level of service, fee structure, and level of capitation. Implications for service delivery are discussed.

Aged↗

Optimal statistical design of radioimmunoassays and competitive protein-binding assays.

The statistical analysis of radioimmunoassay and competitive protein binding assay data is complex. Because the response variable (percent counts) is not lineraly related to log dose, a logit transformation of the response variable usually is performed to permit linear regression analysis. This transformation induces marked heterogeneity of variance, so that iterative weighted regression programs have been used to achieve the best standard curve and the most precise dose estimates of unknowns. In this study several parameters of assay design are investigated in order to establish those designs yielding antigen concentration estimates of highest precision as well as estimates of comparable precision by either simple linear regression analysis or by the more complex weighted regression technique. Unknown estimates of highest precision are obtained when 1) the present counts of the standard doses covers a range of approximately 80 percent to 20 percent, 2) the number of standard dose levels is eight or more, 3) the number of replicates at each dose level is two or more, and 4) the percent counts of the unknowns also are within the range 80 percent ot 20 percent. Under these conditions, also, simple linear regression yields unknown estimates of comparable precision to weighted regression and therefore may be safely used.

Antigens↗

Standard computer programs in statistical analysis of survival in childhood lymphoblastic leukemia.

A material comprising all children in Sweden with acute lymphoblastic leukemia diagnosed in the years 1973-80 was analysed statistically. The total number of children was 505. Studies were made of 38 different variables, using frequency tables, cross tables, life table studies (1) and linear regression analysis according to Cox's method (2,4). Chi-square tests and log rank tests were included in the methods. The combination of life-table studies and linear regression analysis proved to be of value in assessing the significance of different parameters and treatment programs with regard to prognosis. The aim of this paper is to present a method for analysis of a patient material with use of standard computer programs. The results of the total analysis will be published elsewhere (3).

Child↗

Automation of a procedure to find the polynomial which best fits (kappa, c1, c2, T) data of electrolyte solutions by non-linear regression analysis using MATHEMATICA software.

A MATHEMATICA package, 'CONDU.M', has been developed to find the polynomial in concentration and temperature which best fits conductimetric data of the type (kappa, c, T) or (kappa, c1, c2, T) of electrolyte solutions (kappa: specific conductivity; ci: concentration of component i; T: temperature). In addition, an interface, 'TKONDU', has been written in the TCL/Tk language to facilitate the use of CONDU.M by an operator not familiarised with MATHEMATICA. All this software is available on line (UPV/EHU, 2001). 'CONDU.M' has been programmed to: (i) select the optimum grade in c1 and/or c2; (ii) compare models with linear or quadratic terms in temperature; (iii) calculate the set of adjustable parameters which best fits data; (iv) simplify the model by elimination of 'a priori' included adjustable parameters which after the regression analysis result in low statistical significance; (v) facilitate the location of outlier data by graphical analysis of the residuals; and (vi) provide quantitative statistical information on the quality of the fit, allowing a critical comparison among different models. Due to the multiple options offered the software allows testing different conductivity models in a short time, even if a large set of conductivity data is being considered simultaneously. Then, the user can choose the best model making use of the graphical and statistical information provided in the output file. Although the program has been initially designed to treat conductimetric data, it can be also applied for processing data with similar structure, e.g. (P, c, T) or (P, c1, c2, T), being P any appropriate transport, physical or thermodynamic property.

Journal Article↗

Comparative study of the linearity and sensitivity of electron capture and flame photometric detectors using a pesticide standard.

A study was undertaken to compare and evaluate the different types of 63Ni and 3H electron capture (ECD) and flame photometric detectors (FPD) as part of the Canadian Check Sample Program on Pesticide Residue Analysis. Twenty-seven laboratories were supplied with chlorpyrifos standard solutions for the determination of linear range and minimum detectable amounts (MDA). Each laboratory selected its own operating conditions except for the FPD study. Results for the FPD were compared with standardized flame conditions designed to optimize the exponential factor i, the S-mode. The MDA of the ECDs (pulsed and direct-current) ranged from 0.09 to 0.17 pg/sec for 63Ni and 3H sources respectively. The corresponding MDA for the linearized ECDs (pulse modulated or constant current) was 0.04 pg/sec and a linear range of 10(4) or greater with nitrogen as the carried gas. Use of argon/methane and a pulse width of 0.1 usec extended this range to 10(5) but the sensitivity was not as great as with nitrogen carrier gas. The practical limit of detector sensitivity was found to be instrument dependent depending primarily on the noise level. In the FPD study, operating in the P-mode gave an average MDA of 5.97 pg/sec and a linear range of 2 x 10(3). Similarly, the S-mode parameters were 81.1 pg/sec and 8 x 10(2) respectively with an average exponential factor of n 1.8. Attempts to apply optimized detector gas-flow conditions improved sensitivity and linearity in the S-mode only.

Chlorpyrifos↗

The short Sendai virus leader region controls induction of programmed cell death.

The replication of nonsegmented minus-strand RNA genomes, like that of Sendai paramyxovirus (SeV), are controlled by the short leader regions present at each end of the linear genomes and antigenomes; the left and right promoters (PL and PR), respectively. Wild-type SeV is highly cytopathic in cell culture, because it induces programmed cell death (PCD). We have found that a recombinant SeV (rSeVGP42), in which the first 42 nt of le+ sequences at PL were replaced with the equivalent sequences of PR, and which produces infectious virus in amounts comparable to wild type, does not kill cells. Further, the increasing replacement of the terminal le+ sequences at PL with le- sequences led to a decreasing fraction of infected cells being apoptotic. This property (PCD-), moreover, is dominant in cells co-infected with SeVwt and rSeVGP42, and the mutant virus therefore appears to have gained a function which prevents PCD induced by SeVwt. Even though this virus has not been selected for naturally, it excludes SeVwt during co-infections of cultured cells or embryonated chicken eggs. The noncytopathic nature of cells infected or co-infected with rSeVGP42 leads automatically to stable, persistent infections. The mutation in rSeVGP42 is not in the protein coding regions of the viral genome, but in the 55-nt-long leader region which controls antigenome synthesis from genome templates. The SeV leader regions, which are expressed as short RNAs, thus appear to control the induction of PCD.

Animals↗

Analysis of linear trade models and relation to scale economies.

We discuss linear Ricardo models with a range of parameters. We show that the exact boundary of the region of equilibria of these models is obtained by solving a simple integer programming problem. We show that there is also an exact correspondence between many of the equilibria resulting from families of linear models and the multiple equilibria of economies of scale models.

Journal Article↗

[Evaluation method of CT number linearity].

OBJECTIVE: To explore the method for computed tomography (CT) number linearity evaluation. METHODS: The model CTP401 of Catphan500 phantom was adopted to test 43 sets of CT scanners under the same scanning conditions. 1- and 2-order curve fitting of the testing results of each scanner were performed, with the bending of the 2-order fitted curve defined as the degree of CT number non-linearity and the slope of the linear fitting as contrast scale. The 2-norms of the fitting coefficients were calculated for the purpose of fitting quality evaluation. MATLAB 6.1 was employed for programming. RESULTS: The 2-norm of the fitting coefficients of the 2-order fitting curve was approximately 1/10 of that of corresponding linear fitting, indicating that 2-order fitting accorded better to the parent population distribution pattern. The degree of the non-linearity was manifested by the bending of the 2-order fitting curve that increased monotonously with the 2-norm of the corresponding linear fitting. CONCLUSION: It is statistically valid to define CT number non-linearity and contrast scale on the basis of 1 and 2-order fittings of the testing results, which well serves the purpose of quantitative analysis.

Algorithms↗

Setting up waiting-time targets to satisfy patients: an application of mathematical programming.

An out-patient-waiting-time standard has been set up by the government in the Patient's Charter and the standard is supposed to be effective nationwide indiscriminately. This standard is static and does not take into account local variations in patient expectations, patient unpunctualities in keeping their appointments, changing demand, and resource (or budget) constraints. Therefore, it is not surprising that many acute hospitals or Trusts (including the best-known teaching hospitals) have failed to achieve a satisfactory performance against this standard. In this paper, we argue that, while regarding this standard as the government's expectation, local out-patient-waiting-time targets could be set up more comprehensively each year on the basis of prevailing patient expectations, so that the most cost-effective (or optimal) quality is achieved instead of the ideal (or best) quality. We have also developed a mathematical-programming model which can be used to help determine the out-patient waiting-time targets in a systematic way, once the expected degrees of patient satisfaction are specified. A numerical example is provided to illustrate how the model works.

Ambulatory Care↗

Evaluation of a group-based substance abuse treatment program for adolescents.

The effectiveness of adolescent substance abuse treatment has been repeatedly demonstrated, but specific treatment approaches have rarely been sufficiently documented to permit replication. This study evaluated the effectiveness of a manual-guided, outpatient, group-based treatment program for adolescents (N = 194) who were mild-to-moderate substance abusers. In addition to evaluating the group-based treatment model, the study was designed to compare the effectiveness of two approaches to preparing youth to engage in treatment, whereby adolescents received one of two types of treatment induction, either motivational interviewing or counseling overview. Self-reported pretreatment substance use and criminal behaviors were compared with these behaviors 6 and 12 months following treatment entry using a General Linear Mixed Model analytic approach that controlled for the effects of potential confounding variables and examined individual and program factors that might explain treatment response. Participants significantly reduced marijuana use at 6 months, and these reductions were largely sustained at 12 months. No changes in alcohol use or criminal involvement were obtained. Further examination of marijuana use indicated differential treatment response based on participants' emotional abuse history, family satisfaction, school adjustment, and pretreatment substance use frequency. This treatment approach appears promising for marijuana-abusing youth.

Adolescent↗

Analysis of dose-response curves and calculation of agonist dissociation constants using a weighted nonlinear curve fitting program.

The KA value of a full agonist (Furchgott, 1966) is usually calculated following the transformation of a rectangular hyperbolic relationship between equiactive concentrations into a linear relationship via a double reciprocal plot. Such a transformation will introduce error into the value of KA unless the pre- and postinactivation dose-response curves are also rectangular hyperbolas. Nonlinear curve fitting computer programs, which have been developed to evaluate radioligand binding data, fit data to rectangular hyperbolas and, thus, can be used to fit concentration-response data for pre- and postinactivation curves. Examination of (-)-isoprenaline concentration-response curves for positive inotropic effects in left atrial preparations from the guinea pig, established before and after treatment with the irreversible antagonist Ro 03-7894, indicated a marked deviation from the theoretical rectangular hyperbola (Hill coefficient greater than 1). This was accounted for by the presence of a threshold effect. The present study reports on the use of the computer program LIGAND to fit a rectangular hyperbola to the pre- and postinactivation curves for an agonist, while simultaneously calculating and allowing for the presence of a threshold phenomenon. Since both curves are fitted to rectangular hyperbolas, the KA values can be calculated with greater precision than that possible from double reciprocal plots constructed from uncorrected concentration-response curves.

Adrenergic Agonists↗

Peripheral mechanical loading and the mechanism of the tremor of chronic alcoholism.

The tremor of chronic alcoholism, although clinically similar to essential tremor, has been considered a distinct syndrome. Its underlying mechanism was analyzed in five patients (none in the acute stages of alcohol withdrawal) hospitalized in an alcohol detoxification program. All five patients performed tracking tasks in which they pursued a linearly moving "target" light with a response light that they controlled by flexion-extension activity of the wrist. Stationary and dynamic targets were used with both isometric and unconstrained wrist mechanical interfaces. Frequency, torque, and displacement tremor characteristics were examined under varying inertial loading or isometric voluntary torque conditions. Two simultaneous tremor components were present in all patients: a prominent 4- to 7-Hz low-frequency peak and a smaller-amplitude 9.4- to 9.6-Hz high-frequency peak. As the inertia of the hand was augmented during unconstrained tasks, the low-frequency peak decreased, while the high-frequency peak was unaffected. As required voluntary effort was increased during isometric testing, the amplitude of the low-frequency peak increased. These findings suggest that the low-frequency peak represents the significant pathologic component of the tremor of chronic alcoholism and that it has a biomechanical reflex mechanism similar to that of the lower-amplitude normal physiologic tremor.

Adult↗

Vestibular function in children with the CHARGE association.

BACKGROUND: Histopathological examinations and computed tomographic scans of the temporal bone in patients with the CHARGE association (a malformative syndrome that includes coloboma, heart disease, choanal atresia, retarded development, genital hypoplasia, and ear anomalies, including hypoplasia of the external ear and hearing loss) have shown an absence of semicircular canals and a Mondini form of cochlear dysplasia. Until recently, no information was available concerning a possible loss of vestibular function, which could be a factor in retarded posturomotor development. To our knowledge, this is the first report of otolith tests done on patients with the CHARGE association. OBJECTIVE: To test residual vestibular function in patients with the CHARGE association. STUDY DESIGN: In 7 patients with the CHARGE association, we made electro-oculographic recordings of vestibulo-ocular responses to earth-vertical and off-vertical axis rotations to evaluate the function of the canal and the otolith-vestibular systems. RESULTS: None of the 7 patients had semicircular canals in the computed tomographic scan, and none had canal vestibulo-ocular responses to earth-vertical axis rotation, but all had normal otolith vestibulo-ocular responses to the off-vertical axis rotation test. CONCLUSIONS: These results support the hypothesis of a residual functional otolith organ in the hypoplastic posterior labyrinth of children with the CHARGE association. The severe delays in psychomotor development presented by these children are more likely a consequence of multiple factors: canal vestibular deficit, visual impairment, and environmental conditions (long hospital stays and breathing and feeding problems). The remaining sensitivity of the otolith system to gravity and linear acceleration forces in these children could be exploited in early education programs to improve their posturomotor development.

Abnormalities, Multiple↗

Direct determination of mitoxantrone in plasma by high performance liquid chromatography using an automatic precolumn-switching system as sample clean-up procedure.

A high-performance liquid chromatography method which uses direct injection and a column-switching valve for determination of mitoxantrone in plasma is described. After addition of internal standard, plasma was deproteinized by adding 5-sulphosalicylic acid reagent. The supernatant was injected onto an enrichment precolumn flushed with washing solvent (methanol and water 5:95). Absorbed mitoxantrone was backflushed from the precolumn into an analytical column C18 Nucleosil 250 x 4 mm with a gradient elution (solvent A, ammonium formate buffer 1.6 M, pH 4.3; solvent B, acetonitrile and water 40:60; linear gradient from 45 to 55% of B for 30 min was programmed) at a flow rate of 1.3 mL/min. Detection was carried out at 665 nm. This method showed obvious advantages over conventional extraction procedures in terms of speed and facility of sample handling.

Chromatography, High Pressure Liquid↗

Impact of the JOBS intervention on unemployed workers varying in risk for depression.

Reports the results of the JOBS II randomized field experiment that included a sample of 1,801 recent job losers, 671 of which participated in a modified version of the JOBS I intervention for unemployed workers (Caplan, Vinokur, Price, & van Ryn, 1989). The intervention focused on enhancing the sense of mastery through the acquisition of job-search and problem-solving skills, and on inoculation against setbacks. JOBS II was intended to prevent poor mental health and to promote high quality reemployment. The study tested whether the efficacy of the intervention could be increased by screening and oversampling respondents who were at higher risk for a significant increase in depressive symptoms. Results demonstrated that the intervention primarily benefited the reemployment and mental health outcomes of the high-risk respondents. This suggests the feasibility of enhancing the efficacy of this preventive intervention by targeting it for high-risk unemployed workers who could be identified prospectively.

Adult↗

Pharmacokinetics of daunorubicin and daunorubicinol in plasma, P388 and B16 tumours. Comparison with in vitro cytotoxicity data.

The comparison of pharmacokinetics of DNR in mouse plasma, in the DNR naturally resistant B16 melanoma and in the DNR naturally sensitive P388 leukemia showed that there is no direct correlation between total concentrations of this drug in tumours and the sensitivity resistance of these tissues. A finding which demonstrates the inadequacy of distribution models to select new potential anticancer drugs. Cytotoxicity of DNR and its metabolites to B16 melanoma and P388 leukemia cell lines were determined in vitro. Calculated inhibitory concentrations 50 (IC50) were compared to maximal concentrations determined by pharmacokinetic studies. In all cases in vitro IC50 were lower than Cmax values. Moreover, resistant cells in vivo were found to be sensitive to DNR and metabolites when they are propagated in vitro. Tissue concentrations, as well as in vitro data, were fitted to appropriate models by an original program (FADHA) which uses the simplex method to minimize a non-linear cost function. Best fit models were chosen by statistical criteria.

Analysis of Variance↗

Genotype-by-sex interaction in the aetiology of type 2 diabetes mellitus: support for sex-specific quantitative trait loci in Hypertension Genetic Epidemiology Network participants.

AIMS/HYPOTHESIS: While there are sex-related differences in both the prevalence of type 2 diabetes mellitus and disease risk factors, there is only limited research on sex-specific influences on type 2 diabetes aetiology within the same study population. Thus, we assessed genotype-by-sex interaction using a liability threshold model in an attempt to localise sex-specific type 2 diabetes quantitative trait loci (QTLs). SUBJECTS, MATERIALS AND METHODS: Hypertensive siblings and their offspring and/or parents in the Hypertension Genetic Epidemiology Network of the Family Blood Pressure Program were recruited from five field centres. The diabetic phenotype was adjusted for race, study centre, age and non-linear age effects. In total, 567 diabetic individuals were identified in 385 families. Variance component linkage analyses in the combined sample and stratified by sex and race were performed (SOLAR program) using race-specific marker allele frequencies derived from a random sample of participants at each centre. RESULTS: We observed a QTL-specific genotype-by-sex interaction (p=0.009) on chromosome 17 at 31 cM, with females displaying a robust adjusted logarithm of odds (LOD) of 3.0 compared with 0.2 in males and 1.3 in the combined sample. Three additional regions demonstrating suggestive evidence for linkage were detected: chromosomes 2 and 5 in the female sample and chromosome 22 (adjusted LOD=1.9) in the combined sample. CONCLUSIONS/INTERPRETATION: These findings suggest that multiple genes may regulate susceptibility to type 2 diabetes, demonstrating the importance of considering the interaction of genes and environment in the aetiology of common complex traits.

Adult↗

Economic burden of hepatitis C in Canada and the potential impact of prevention. Results from a disease model.

This Canadian hepatitis C model estimates economic burden of disease using Markov modeling to predict progression over 11 health states annually from 2001 to 2040. Incidence-based estimates help demonstrate the capability to determine cost-effectiveness of programs to prevent different proportions of incident cases. Benefits of prevention increase linearly with the number of incident cases prevented. The model forecasts annual health care costs for the treatment of HCV-related disease ranging from $103 to $158 million over time. Health care costs attributable to 2001 incidence cohort are forecast at $14.6 million for prevention. The increasing cost of HCV provides a framework for further analysis and implementation of long-term policies aimed at appropriate allocation of resources for health in Canada.

Canada↗