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PubMed1998

Procedures for estimating growth rates in thoracic aortic aneurysms.

Thoracic aortic aneurysms (TAAs) are potentially lethal medical conditions often requiring surgical intervention. Reliable information on TAA growth rates and associated risk factors is important for managing this challenging patient population. Unfortunately, a number of studies have employed questionable statistical methods, leading to biased and imprecise estimates. The present study describes these statistical problems in existing studies and delineates procedures for obtaining more reliable results. Using data from the Yale Center for Thoracic Aortic Disease, the study compares TAA growth rate estimates using conventional methods versus the recommended approach of instrumental variables (IV) estimation. The IV approach is designed to mitigate problems of measurement errors inherent in existing estimates of TAA growth. The results demonstrate that IV estimation yields more robust and precise estimates of TAA growth rates and risk factors for TAA growth. For example, the conventional approach yields TAA growth rates that fluctuate substantially-from 0.12 cm/yr to 0.90 cm/yr-depending on (1) the minimum serial follow-up period for patient inclusion in the study and (2) how subjects with negative measured growth rates are handled. In contrast, growth rate estimates using the IV approach are much more robust, ranging from 0.12 to 0.13 cm/yr. The 95% confidence intervals of estimated TAA growth are much more compact using the IV approach as well. We conclude that the IV estimation procedure yields more reliable estimates of TAA growth than does the conventional approach.

Aortic Aneurysm, Thoracic↗

PubMed1996

Earnings and schooling: an overview of economic research based on the Australian Twin Register.

This paper reviews four economic studies of aspects of earnings and schooling conducted by the authors using data from the Australian Twin Register. First, estimates of the economic returns to schooling made using fixed effects and selection effects regression models incorporating an instrumental variables approach to correct for measurement error in self-reported schooling levels are examined. The finding is that up to 30 per cent of the estimated return to schooling may be due to family effects and the remainder to pure educational effects. Second, comparisons are made between the economic model of Ashenfelter and Krueger (1994) and that of DeFries and Fulker (1985) and the results obtained from each are shown to be similar. Third, gender differences in returns to schooling are estimated and family effects are found to be a more important influence in the case of males. Fourth, the influence of family effects on educational attainments is considered and it is found that around one-half of educational attainment is accounted for by genetic inheritance and up to another quarter due to shared environment effects.

Australia↗

PubMed2003

High-throughput screening of selectivity of melt polymerization catalysts using fluorescence spectroscopy and two-wavelength fluorescence imaging.

A new general approach for rapid assessment of polymerization catalysts is introduced. Native fluorescence emission of solid polymers is measured directly in combinatorial 96-microreactor arrays and polymers produced in a laboratory-scale validation reactor. Fluorescence features collected with a CCD-based spectrofluorometer are correlated with chemical properties of interest such as polymer molecular weight, amount of branching, and catalyst selectivity. The approach is illustrated by screening of selectivity of melt polymerization catalysts used in synthesis of an aromatic bisphenol A polycarbonate. Selectivity of catalysts correlated with the ratio of fluorescence intensities at 400 and 500 nm at 340-nm excitation. The relative standard deviation (RSD) in spectroscopic serial measurements was 1-12.5%. This spread included instrument variability (< or = 1% RSD) and sample inhomogeneity. Parallel quantitative screening of catalyst selectivity in combinatorial 96-microreactor arrays was performed as a two-wavelength ratiometric fluorescence imaging through 400- and 500-nm interference filters and showed a good correlation (R2 = 0.994) with serial screening. Our approach is an attractive alternative to traditional separation-based techniques if speed and nondestructive nature of analysis are critical and when the high cross-linking or solvent resistance of polymers complicates traditional analysis.

Journal Article↗

PubMed2007

Quantification of diacylglycerol species from cellular extracts by electrospray ionization mass spectrometry using a linear regression algorithm.

Diacylglycerols (DAGs) play significant roles in both intermediate metabolism and signal transduction. These lipid species are second messengers involved in modulating a plethora of cellular processes. Evaluation of DAG species concentrations has been hampered by the lack of a reliable method for molecular species analysis within a complex mixture of cellular lipids. We describe a new method for quantitative analysis of DAG species from complex biological extracts based on positive mode electrospray ionization mass spectrometry without prior derivatization. Quantification is achieved using internal standards and calibration curves constructed by spiking cell extracts with different concentrations of DAG species containing various acyl chain lengths and degrees of unsaturation. The new mass spectral data processing algorithm incorporates a multiple linear regression model including a factor accountable for possible interactions between experimental preparations and the slope of the curve for the standards, allowing the examinations of the effects of sample origin conditions (such as cell types, phenotypes, etc.) and instrument variability on this slope. Internal standards provide a basis for quantification of 28 DAG molecular species detected in RAW 264.7 cells after stimulation of a G-protein coupled receptor with platelet activating factor. This method displays excellent reproducibility over the established range of concentrations with variations of < or =10% and is highly sensitive with a detection limit of 0.1-0.4 pmol/microL depending upon acyl chain composition. We have shown differential effects on various DAGs in response to a ligand which illustrates the importance of examining lipids at the molecular species level rather than as a single homogeneous entity.

Algorithms↗

PubMedDate not supplied

Peak alignment of urine NMR spectra using fuzzy warping.

Proton nuclear magnetic resonance (1H NMR) spectroscopic analysis of mixtures has been used extensively for a variety of applications ranging from the analysis of plant extracts, wine, and food to the evaluation of toxicity in animals. For example, NMR analysis of urine samples has been used extensively for biomarker discovery and, more simply, for the construction of classification models of toxicity, disease, and biochemical phenotype. However, NMR spectra of complex mixtures typically show unwanted local peak shifts caused by matrix and instrument variability, which must be compensated for prior to statistical analysis and interpretation of the data. One approach is to align the spectral peaks across the data set. An efficient and fast warping algorithm is required as the signals typically contain ca. 32,000-64,000 data points and there can be several thousand spectra in a data set. As demonstrated in our study, the iterative fuzzy warping algorithm fulfills these requirements and can be used on-line for an alignment of the NMR spectra. Correlation coefficients between the aligned and target spectra are used as the evaluation function for the algorithm, and its performance is compared with those of other published warping methods.

Algorithms↗

PubMed2006

Analysis of pharmaceuticals in water by isotope dilution liquid chromatography/tandem mass spectrometry.

A method has been developed for the trace analysis of 15 pharmaceuticals, four metabolites of pharmaceuticals, three potential endocrine disruptors, and one personal care product in various waters. The method employs solid-phase extraction (SPE) and liquid chromatography/tandem mass spectrometry (LC-MS/MS), using electrospray ionization (ESI) in both positive and negative modes. Unlike many previous LC-MS/MS methods, which suffer from matrix suppression, this method uses isotope dilution for each compound to correct for matrix suppression, as well as SPE losses and instrument variability. The method was tested in five matrices, and results indicate that the method is very robust. Matrix spike recoveries for all compounds were between 88 and 106% for wastewater influent, 85 and 108% for wastewater effluent, 72 and 105% for surface water impacted by wastewater, 96 and 113% for surface water, and 91 and 116% for drinking water. The method reporting limits for all compounds were between 0.25 and 1.0 ng/L, based on 500 mL of sample extracted and a final extract volume of 500 microL. Occurrence of the compounds in all five matrices is also reported.

Chemistry Techniques, Analytical↗

PubMed2000

HAI-RTP determination of carbaryl pesticide in different irrigation water samples of south Spain.

In this work, a widely used pesticide named carbaryl, present in numerous water supplies, has been determined by the so-called heavy atom induced room-temperature phosphorescence (HAI-RTP) methodology. A detailed study of numerous instrumental variables such as sensitivity, slits, decay time, and gate time, and those of experimental type such as heavy atoms, oxygen scavenger, temperature, buffer solutions, and organic solvents, have been carried out. The detection limit was 2.8 ng mL(-)(1) with a relative standard deviation of 2.12% at the 150 ng mL(-)(1) level. Spiked irrigation water samples taken from different places near agricultural fields gave mean percentage recoveries of 95.7%. The results obtained in this study indicate that the proposed method is suitable for the determination of residues of carbaryl pesticide in water samples with good reproducibility and sensitivity for the analysis of this compound being rapid and very simple for routine analysis.

Carbaryl↗

PubMed2000

Measurement error in prenatal care utilization: evidence of attenuation bias in the estimation of impact on birth weight.

OBJECTIVE: Errors in the measurement of the timing and number of prenatal care visits may produce downward bias in estimates of the impact of prenatal care use on birth outcomes. This paper examines the extent of attenuation bias from measurement error in the estimation of the effect of prenatal care use on birth weight. METHODS: Data were analyzed from the 1980 National Natality Survey, a nationally representative sample of live births with information on prenatal care utilization from three sources: birth certificates, medical provider surveys, and maternal surveys. The extent of attenuation bias in estimates of the impact of different measures of prenatal care use on birth weight was examined by comparing estimates robust to measurement error (including instrumental variables) with ordinary least squares results. RESULTS: There is considerable disagreement in measures of prenatal care across the three data sources, with correlations in the utilization measures computed from different sources around 0.5. The results also show evidence of attenuation bias from measurement error in estimates of the impact of prenatal care on birth weight for both White and Black mothers. Attenuation bias was least severe for information from the birth certificate report of prenatal care. CONCLUSIONS: Because of measurement error, previous studies may have underestimated the effect of prenatal care utilization on birth weight. Corrected estimates, however, do not suggest that prenatal care is a major predictor of birth weight. In addition, part of what previous analyses have interpreted as adverse selection bias may in fact be attenuation bias due to measurement error.

Birth Weight↗

PubMed2002

Dose response in child and adolescent mental health services.

This study examines the dose-response relationship, the correlation between the amount of mental health treatment a child receives (dose) and the outcome (response) in a community setting. Participants were 125 children treated in the Stark County Child and Adolescent Mental Health System. Study methods include multiple outcomes, multiple-dose definitions, longitudinal hierarchical analysis of repeated measures, and instrumental variable estimation to control for possible confounding between outcome and treatment dose. Results show no statistically significant dose response. The results do not support the existence of a dose response for children and adolescents consistent enough to guide clinicians, administrators, or policymakers.

Adolescent↗

PubMed2002

Research development mechanisms.

Studies designed to reduce the burden of affective disorders should apply and develop theories and methods from diverse social sciences that could strengthen current interventions. A series of papers from diverse fields, such as quality engineering, behavioral economics, etc. might be a needed first step. Methodological research on design strategies such as group-level randomized trials, or instrumental variables analyses are needed. Finaly, qualitative studies to understand diverse stakeholder views are also needed. To pursue these areas, interdisciplinary training programs are needed to develop skilled researchers to study communities and community-based delivery settings. New research infrastructures are needed to support community and research collaborations, as well as supporting development of new technologies to enable diffusion of care.

Cost of Illness↗

PubMed2000

Multicentre study for the development of an in vivo model to evaluate the influence of topical formulations on irritation.

Although skin protective products to prevent irritant skin reactions are in wide use, neither standardized test models to prove differences in efficacy exist, nor has the quality or the reproducibility of results been evaluated in a multicentre approach. This should be mandatory when developing or testing skin care products. Therefore, we have designed a multicentre study in an approach to find a standardized test procedure for the evaluation of skin protective products. In this irritation study, a repeated short-time occlusive irritation test (ROIT) with a standardized protocol has been evaluated in 2 phases (12 days and 5 days protocol) in 4 (n=20) respectively 6 (n=33) skilled centres. The skin reaction was induced by 2 irritants (0.5% aq. SLS and toluene, 2x a day for 30 min). Its modification by 3 different cream bases with different hydrophilicity was analyzed. The irritation was monitored by bioengineering methods (TEWL measurement, colorimetry) and by clinical scoring. The evaluation showed that significant results could already be achieved with the 5-day protocol. Furthermore, in spite of the expected inter-centre variations due to heterogeneity of the individual threshold of irritation, interpretation of clinical score, and inter-instrumental variability, the ranking of the vehicles regarding reduction of the irritant reaction was consistent in all centres.

Administration, Topical↗

PubMed1993

Automated kinetic-spectrofluorimetric method for the determination of morphine in urine.

The continuous addition of reagent technique was used with spectrofluorimetric detection for the kinetic determination of morphine in urine samples. The method thus developed is based on the oxidative dimerization of morphine to fluorescent pseudomorphine by potassium hexacyanoferrate(III) in a basic medium. The optimum pH, oxidant concentration and instrumental variables were determined. The method permits the sensitive determination of morphine over a wide concentration range (15-925 ng ml-1) with high precision (relative standard deviation approximately 2%), selectivity and sample throughput (48 samples h-1). A novel sorption--desorption procedure was used to isolate morphine from whole urine, which provided recoveries of between 85 and 100%. The results showed the usefulness of the proposed method for controlling a wide variety of medicinal problems (e.g., therapeutic, overdose and doping analysis).

Autoanalysis↗

PubMed2002

Flow analysis-hydride generation-Fourier transform infrared spectrometry. A new analytical technique for the simultaneous determination of antimony, arsenic and tin.

The combination of flow analysis (FA), hydride generation (HG) and Fourier transform infrared (FTIR) spectrometry is proposed as a novel and powerful analytical technique for the individual and simultaneous determination of antimony, arsenic and tin in aqueous samples. The analytes were transformed into the volatile hydride form by on-line reaction with sodium tetrahydroborate in acidic medium. The gaseous analyte hydrides [M(n)H(m), (g)] generated, were transported by means of a carrier gas stream inside the IR gas cell and the corresponding FTIR spectrum was acquired in a continuous mode. The 1893, 1904 and 2115 cm(-1) bands of the SbH3, SnH4, and AsH3 were selected for the determination of antimony, tin and arsenic, respectively. The limit of detection (3sigma) obtained by using a short-path (10 cm) IR gas cell were 0.25, 0.30 and 1.2 mg l(-1) for the determination of antimony, tin and arsenic, respectively; while the precision (relative standard deviation, RSD, n 5) found from a standard solution containing 50 mg l(-1) of each element was, in all cases, less than 0.3%. However, the use of a long-path (7.25 m) IR gas cell improved the figures of merit (sensitivity, limits of detection and quantification) nearly 60-fold. The effect of the main experimental and instrumental variables, such as acidic media, sodium tetraborohydrate concentration, nitrogen flow rate, nominal resolution and the scan accumulation on the analytical signals of the antimony, tin and arsenic hydrides, were studied. Further, the potential of the proposed technique for the simultaneous determination of these elements was tested, analyzing synthetic samples containing different amounts of Sb, Sn and As.

Antimony↗

PubMed2001

Relationship of unrecognised myocardial infarction, diabetes mellitus and type of surgery to postoperative cardiac outcomes in vascular surgery.

OBJECTIVES: to evaluate preoperative clinical, surgical and instrumental variables as predictors of postoperative cardiac events in patients undergoing different types of elective major vascular surgery. MATERIAL AND METHODS: on the basis of an algorithm including clinical and test echocardiographic data, we prospectively stratified 604 consecutive patients into low, intermediate and high-risk groups. The value of the variables in predicting postoperative cardiac events was assessed by means of multivariate analysis. RESULTS: there were 16 major postoperative cardiac events and six of 16 postoperative deaths were cardiac related (1%). Significant predictors of cardiac complications were unrecognised myocardial infarction (odds ratio - (OR) 5.6), coronary artery disease (OR 2.5), severe hypertension (OR 2.1) and peripheral vascular surgery (OR 1.9). In the intermediate-risk group, the best correlates with cardiac complications were unrecognised myocardial infarction (OR 3.3) and diabetes (OR 2.5). CONCLUSIONS: our results suggest the importance of identifying patients with unrecognised ischaemic heart disease and of using aggressive perioperative protocols for managing diabetic patients undergoing peripheral vascular procedures.

Aged↗

PubMed1996

Are the returns to technological change in health care declining?

Whether the U.S. health care system supports too much technological change-so that new technologies of low value are adopted, or worthwhile technologies become overused-is a controversial question. This paper analyzes the marginal value of technological change for elderly heart attack patients in 1984-1990. It estimates the additional benefits and costs of treatment by hospitals that are likely to adopt new technologies first or use them most intensively. If the overall value of the additional treatments is declining, then the benefits of treatment by such intensive hospitals relative to other hospitals should decline, and the additional costs of treatment by such hospitals should rise. To account for unmeasured changes in patient mix across hospitals that might bias the results, instrumental-variables methods are used to estimate the incremental mortality benefits and costs. The results do not support the view that the returns to technological change are declining. However, the incremental value of treatment by intensive hospitals is low throughout the study period, supporting the view that new technologies are overused.

Aged↗

PubMed2025

Circulating inflammatory proteins as causal drivers and therapeutic targets in asthma: insights from genetic and pathway-based analyses.

OBJECTIVE: To identify circulating inflammatory proteins with potential causal roles in asthma development through integrated genetic and pathway-based analyses, and to evaluate their potential as therapeutic targets. METHODS: We used genetically anchored instrumental variables from 180 protein quantitative trait loci (pQTLs) to assess the causal effects of 91 circulating inflammatory proteins on asthma risk, using large-scale GWAS datasets. Analytical robustness was evaluated through pleiotropy and heterogeneity testing. Functional enrichment and literature-based pathway analyses were performed to support biological plausibility and validate findings. RESULTS: Four proteins showed significant causal effects on asthma: CCL19 and LIFR were protective (OR = 0.89 and 0.91, p ≤ 6.8E-03), while ARTN and IL6 were associated with increased risk (OR = 1.15 and 1.18, p ≤ 1.1E-04). We also identified reverse causal effects of asthma on 11 cytokines, including MMP10, TGFB1, IL33, and IL18R1. Most of these proteins were enriched in pathways related to cytokine signaling and immune response (p < 0.001). All identified proteins had prior literature support linking them to asthma or airway inflammation. CONCLUSIONS: Our findings highlight a subset of circulating inflammatory proteins that are likely causal in asthma pathogenesis and may serve as promising targets for therapeutic intervention. These results offer novel insights into the immunological mechanisms underlying asthma and support the utility of genetic causal inference in target prioritization.

Asthma↗

PubMed2025

Dietary antioxidants: a challenge or an opportunity for asthma? Genetic insights from a Two-sample mendelian randomization study.

BACKGROUND: Oxidative stress is crucial in the immune response and airway inflammatory process associated with asthma. While the relationship between dietary antioxidants and asthma remains debated in observational studies, this study uses two-sample Mendelian randomization (MR) to explore a potential causal link. METHODS: We acquired six distinct categories of absolute circulating antioxidants and five different types of metabolic circulating antioxidants from the most recent genome-wide association study data of the European population, including vitamin A (retinol), vitamin C (ascorbic acid), vitamin E (tocopherol), β-carotene, lycopene, and urate. The latest data regarding asthma was obtained from the FinnGen database. We utilized single nucleotide polymorphisms as instrumental variables to conduct five MR methods. To confirm the accuracy of the results, additional sensitivity analyses were performed to eliminate any potential confounding factors, such as heterogeneity and pleiotropy. RESULTS: MR and sensitivity analyses revealed an association between circulating urate and asthma, suggesting a potential increase in asthma risk (OR = 1.090; 95% CI = 1.030-1.150; p = 0.004). No causal relationship was found for other antioxidants. CONCLUSIONS: This MR analysis suggested that genetically determined circulating urate may increase asthma risk. Further large-scale randomized controlled trials and mediated MR analysis are needed to explore underlying mechanisms.

Humans↗

PubMed2006

Price responsiveness of demand for cigarettes: does rationality matter?

Meta-analysis is applied to aggregate-level studies that model the demand for cigarettes using static, myopic, or rational addiction frameworks in an attempt to synthesize key findings in the literature and to identify determinants of the variation in reported price elasticity estimates across studies. The results suggest that the rational addiction framework produces statistically similar estimates to the static framework but that studies that use the myopic framework tend to report more elastic price effects. Studies that applied panel data techniques or controlled for cross-border smuggling reported more elastic price elasticity estimates, whereas the use of instrumental variable techniques and time trends or time dummy variables produced less elastic estimates. The finding that myopic models produce different estimates than either of the other two model frameworks underscores that careful attention must be given to time series properties of the data.

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