Comparing meta-analysis and ecological-longitudinal analysis in time-series studies: a case study of the effects of air pollution on mortality in three Spanish cities

The objective of this paper is to introduce a diVerent approach, called the ecological-longitudinal, to carrying out pooled analysis in time series ecological studies. Because it gives a larger number of data points and, hence, increases the statistical power of the analysis, this approach, unlike conventional ones, allows the complementation of aspects such as accommodation of random effect models, of lags, of interaction between pollutants and between pollutants and meteorological variables, that are hardly implemented in conventional approaches. Design—The approach is illustrated by providing quantitative estimates of the short-termeVects of air pollution on mortality in three Spanish cities, Barcelona,Valencia and Vigo, for the period 1992–1994. Because the dependent variable was a count, a Poisson generalised linear model was first specified. Several modelling issues are worth mentioning. Firstly, because the relations between mortality and explanatory variables were nonlinear, cubic splines were used for covariate control, leading to a generalised additive model, GAM. Secondly, the effects of the predictors on the response were allowed to occur with some lag. Thirdly, the residual autocorrelation, because of imperfect control, was controlled for by means of an autoregressive Poisson GAM. Finally, the longitudinal design demanded the consideration of the existence of individual heterogeneity, requiring the consideration of mixed models. Main results—The estimates of the relative risks obtained from the individual analyses varied across cities, particularly those associated with sulphur dioxide. The highest relative risks corresponded to black smoke in Valencia. These estimates were higher than those obtained from the ecological-longitudinal analysis. Relative risks estimated from this latter analysis were practically identical across cities, 1.00638 (95% confidence intervals 1.0002, 1.0011) for a black smoke increase of 10 μg/m3 and 1.00415 (95% CI 1.0001, 1.0007) for a increase of 10 μg/m3 of sulphur dioxide. Because the statistical power is higher than in the individual analysis more interactions were statistically significant,especially those among air pollutants and meteorological variables. Conclusions—Air pollutant levels were related to mortality in the three cities of the study, Barcelona, Valencia and Vigo. These results were consistent with similar studies in other cities, with other multicentric studies and coherent with both, previous individual, for each city, and multicentric studies for all three cities

Underestimation of Standard Errors in Multi-Site Time Series Studies

Multi-site time series studies of air pollution and mortality and morbidity have figured prominently in the literature as comprehensive approaches for estimating acute effects of air pollution on health. Hierarchical models are generally used to combine site-specific information and estimate pooled air pollution effects taking into account both within-site statistical uncertainty, and across-site heterogeneity. Within a site, characteristics of time series data of air pollution and health (small pollution effects, missing data, highly correlated predictors, non linear confounding etc.) make modelling all sources of uncertainty challenging. One potential consequence is underestimation of the statistical variance of the site-specific effects to be combined. In this paper we investigate the impact of variance underestimation on the pooled relative rate estimate. We focus on two-stage normal-normal hierarchical models and on under- estimation of the statistical variance at the first stage. By mathematical considerations and simulation studies, we found that variance underestimation does not affect the pooled estimate substantially. However, some sensitivity of the pooled estimate to variance underestimation is observed when the number of sites is small and underestimation is severe. These simulation results are applicable to any two-stage normal-normal hierarchical model for combining information of site-specific results, and they can be easily extended to more general hierarchical formulations. We also examined the impact of variance underestimation on the national average relative rate estimate from the National Morbidity Mortality Air Pollution Study and we found that variance underestimation as much as 40% has little effect on the national average.

Ozone and Mortality: A Meta-Analysis of Time-Series Studies and Comparison to a Multi-City Study (The National Morbidity, Mortality, and Air Pollution Study)

While many time-series studies of ozone and daily mortality identified positive associations,others yielded null or inconclusive results. We performed a meta-analysis of 144 effect estimates from 39 time-series studies, and estimated pooled effects by lags, age groups,cause-specific mortality, and concentration metrics. We compared results to estimates from the National Morbidity, Mortality, and Air Pollution Study (NMMAPS), a time-series study of 95 large U.S. cities from 1987 to 2000. Both meta-analysis and NMMAPS results provided strong evidence of a short-term association between ozone and mortality, with larger effects for cardiovascular and respiratory mortality, the elderly, and current day ozone exposure as compared to other single day lags. In both analyses, results were not sensitive to adjustment for particulate matter and model specifications. In the meta-analysis we found that a 10 ppb increase in daily ozone is associated with a 0.83 (95% confidence interval: 0.53, 1.12%) increase in total mortality, whereas the corresponding NMMAPS estimate is 0.25%(0.12, 0.39%). Meta-analysis results were consistently larger than those from NMMAPS,indicating publication bias. Additional publication bias is evident regarding the choice of lags in time-series studies, and the larger heterogeneity in posterior city-specific estimates in the meta-analysis, as compared with NMAMPS.

An alternative approach to deal with the absence of clinical trials: a proportional meta-analysis of case series studies

PURPOSE: Systematic reviews are criticized for frequently offering inconsistent evidences and absence of straightforward recommendations. Their value seems to be depreciated when the conclusions are uncertain. To describe an alternative approach of evaluating case series studies in health care when there is absence of clinical trials. METHODS: We provide illustrations from recent experiences. Proportional meta-analysis was performed on surgical outcomes: (a) case series studies, (b) use of cryoablation or radiofrequency ablation, and (c) patients with small renal cell carcinoma. The statistically significant difference between both interventions studied was defined if their combined 95% confidential interval (CI) did not overlap. RESULTS: As demonstrated by the example, this analysis is an alternative approach to provide some evidence of the intervention´s effects under evaluation and plotting all available case series in the absence of clinical trials for the health field. CONCLUSIONS: Although we are leading to a low level of evidence to determine efficacy, effectiveness and safety of interventions this alternative approach can help surgeons, physicians and health professionals for a provisionally decision in health care along with their clinical expertise and the patient´s wishes and circumstances in the absence of high-quality primary studies. It´s not a replacement for the gold standard randomized clinical trial, but an alternative analysis for clinical research.

Improving GPS time series for geodynamic studies

Accurate and stable time series of geodetic parameters can be used to help in understanding the dynamic Earth and its response to global change. The Global Positioning System, GPS, has proven to be invaluable in modern geodynamic studies. In Fennoscandia the first GPS networks were set up in 1993. These networks form the basis of the national reference frames in the area, but they also provide long and important time series for crustal deformation studies. These time series can be used, for example, to better constrain the ice history of the last ice age and the Earth s structure, via existing glacial isostatic adjustment models. To improve the accuracy and stability of the GPS time series, the possible nuisance parameters and error sources need to be minimized. We have analysed GPS time series to study two phenomena. First, we study the refraction in the neutral atmosphere of the GPS signal, and, second, we study the surface loading of the crust by environmental factors, namely the non-tidal Baltic Sea, atmospheric load and varying continental water reservoirs. We studied the atmospheric effects on the GPS time series by comparing the standard method to slant delays derived from a regional numerical weather model. We have presented a method for correcting the atmospheric delays at the observational level. The results show that both standard atmosphere modelling and the atmospheric delays derived from a numerical weather model by ray-tracing provide a stable solution. The advantage of the latter is that the number of unknowns used in the computation decreases and thus, the computation may become faster and more robust. The computation can also be done with any processing software that allows the atmospheric correction to be turned off. The crustal deformation due to loading was computed by convolving Green s functions with surface load data, that is to say, global hydrology models, global numerical weather models and a local model for the Baltic Sea. The result was that the loading factors can be seen in the GPS coordinate time series. Reducing the computed deformation from the vertical time series of GPS coordinates reduces the scatter of the time series; however, the long term trends are not influenced. We show that global hydrology models and the local sea surface can explain up to 30% of the GPS time series variation. On the other hand atmospheric loading admittance in the GPS time series is low, and different hydrological surface load models could not be validated in the present study. In order to be used for GPS corrections in the future, both atmospheric loading and hydrological models need further analysis and improvements.

Studies on Binary Time Series Models with Applications to Empirical Macroeconomics and Finance

This thesis studies binary time series models and their applications in empirical macroeconomics and finance. In addition to previously suggested models, new dynamic extensions are proposed to the static probit model commonly used in the previous literature. In particular, we are interested in probit models with an autoregressive model structure. In Chapter 2, the main objective is to compare the predictive performance of the static and dynamic probit models in forecasting the U.S. and German business cycle recession periods. Financial variables, such as interest rates and stock market returns, are used as predictive variables. The empirical results suggest that the recession periods are predictable and dynamic probit models, especially models with the autoregressive structure, outperform the static model. Chapter 3 proposes a Lagrange Multiplier (LM) test for the usefulness of the autoregressive structure of the probit model. The finite sample properties of the LM test are considered with simulation experiments. Results indicate that the two alternative LM test statistics have reasonable size and power in large samples. In small samples, a parametric bootstrap method is suggested to obtain approximately correct size. In Chapter 4, the predictive power of dynamic probit models in predicting the direction of stock market returns are examined. The novel idea is to use recession forecast (see Chapter 2) as a predictor of the stock return sign. The evidence suggests that the signs of the U.S. excess stock returns over the risk-free return are predictable both in and out of sample. The new "error correction" probit model yields the best forecasts and it also outperforms other predictive models, such as ARMAX models, in terms of statistical and economic goodness-of-fit measures. Chapter 5 generalizes the analysis of univariate models considered in Chapters 2 4 to the case of a bivariate model. A new bivariate autoregressive probit model is applied to predict the current state of the U.S. business cycle and growth rate cycle periods. Evidence of predictability of both cycle indicators is obtained and the bivariate model is found to outperform the univariate models in terms of predictive power.

Parallel Time Series Analysis and Income Inequality: A New Approach to Comparative Case Studies

This case study deals with the role of time series analysis in sociology, and its relationship with the wider literature and methodology of comparative case study research. Time series analysis is now well-represented in top-ranked sociology journals, often in the form of ‘pooled time series’ research designs. These studies typically pool multiple countries together into a pooled time series cross-section panel, in order to provide a larger sample for more robust and comprehensive analysis. This approach is well suited to exploring trans-national phenomena, and for elaborating useful macro-level theories specific to social structures, national policies, and long-term historical processes. It is less suited however, to understanding how these global social processes work in different countries. As such, the complexities of individual countries - which often display very different or contradictory dynamics than those suggested in pooled studies – are subsumed. Meanwhile, a robust literature on comparative case-based methods exists in the social sciences, where researchers focus on differences between cases, and the complex ways in which they co-evolve or diverge over time. A good example of this is the inequality literature, where although panel studies suggest a general trend of rising inequality driven by the weakening power of labour, marketisation of welfare, and the rising power of capital, some countries have still managed to remain resilient. This case study takes a closer look at what can be learned by applying the insights of case-based comparative research to the method of time series analysis. Taking international income inequality as its point of departure, it argues that we have much to learn about the viability of different combinations of policy options by examining how they work in different countries over time. By taking representative cases from different welfare systems (liberal, social democratic, corporatist, or antipodean), we can better sharpen our theories of how policies can be more specifically engineered to offset rising inequality. This involves a fundamental realignment of the strategy of time series analysis, grounding it instead in a qualitative appreciation of the historical context of cases, as a basis for comparing effects between different countries.

Multivariate analyses of variance and covariance for simulation studies involving normal time series

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Genetic time-series analysis identifies a major QTL for in vivo alcohol metabolism not predicted by in vitro studies of structural protein polymorphism at the ADH1B or ADH1C loci

After ingestion of a standardized dose of ethanol, alcohol concentrations were assessed, over 3.5 hours from blood (six readings) and breath (10 readings) in a sample of 412 MZ and DZ twins who took part in an Alcohol Challenge Twin Study (ACTS). Nearly all participants were subsequently genotyped on two polymorphic SNPs in the ADH1B and ADH1C loci known to affect in vitro ADH activity. In the DZ pairs, 14 microsatellite markers covering a 20.5 cM region on chromosome 4 that includes the ADH gene family were assessed, Variation in the timed series of autocorrelated blood and breath alcohol readings was studied using a bivariate simplex design. The contribution of a quantitative trait locus (QTL) or QTL's linked to the ADH region was estimated via a mixture of likelihoods weighted by identity-by-descent probabilities. The effects of allelic substitution at the ADH1B and ADH1C loci were estimated in the means part of the model simultaneously with the effects sex and age. There was a major contribution to variance in alcohol metabolism due to a QTL which accounted for about 64% of the additive genetic covariation common to both blood and breath alcohol readings at the first time point. No effects of the ADH1B*47His or ADH1C*349Ile alleles on in vivo metabolism were observed, although these have been shown to have major effects in vitro. This implies that there is a major determinant of variation for in vivo alcohol metabolism in the ADH region that is not accounted for by these polymorphisms. Earlier analyses of these data suggested that alcohol metabolism is related to drinking behavior and imply that this QTL may be protective against alcohol dependence.

The short-term effect of air pollution on cardiovascular mortality in Tianjin, China : comparison of time series and case–crossover analyses

Background: Many studies have illustrated that ambient air pollution negatively impacts on health. However, little evidence is available for the effects of air pollution on cardiovascular mortality (CVM) in Tianjin, China. Also, no study has examined which strata length for the time-stratified case–crossover analysis gives estimates that most closely match the estimates from time series analysis. Objectives: The purpose of this study was to estimate the effects of air pollutants on CVM in Tianjin, China, and compare time-stratified case–crossover and time series analyses. Method: A time-stratified case–crossover and generalized additive model (time series) were applied to examine the impact of air pollution on CVM from 2005 to 2007. Four time-stratified case–crossover analyses were used by varying the stratum length (Calendar month, 28, 21 or 14 days). Jackknifing was used to compare the methods. Residual analysis was used to check whether the models fitted well. Results: Both case–crossover and time series analyses show that air pollutants (PM10, SO2 and NO2) were positively associated with CVM. The estimates from the time-stratified case–crossover varied greatly with changing strata length. The estimates from the time series analyses varied slightly with changing degrees of freedom per year for time. The residuals from the time series analyses had less autocorrelation than those from the case–crossover analyses indicating a better fit. Conclusion: Air pollution was associated with an increased risk of CVM in Tianjin, China. Time series analyses performed better than the time-stratified case–crossover analyses in terms of residual checking.

The impact of nonlinear exposure risk relationships on seasonal time series data: modelling danish neonatal birth anthropometric data

Background Birth weight and length have seasonal fluctuations. Previous analyses of birth weight by latitude effects identified seemingly contradictory results, showing both 6 and 12 monthly periodicities in weight. The aims of this paper are twofold: (a) to explore seasonal patterns in a large, Danish Medical Birth Register, and (b) to explore models based on seasonal exposures and a non-linear exposure-risk relationship. Methods Birth weight and birth lengths on over 1.5 million Danish singleton, live births were examined for seasonality. We modelled seasonal patterns based on linear, U- and J-shaped exposure-risk relationships. We then added an extra layer of complexity by modelling weighted population-based exposure patterns. Results The Danish data showed clear seasonal fluctuations for both birth weight and birth length. A bimodal model best fits the data, however the amplitude of the 6 and 12 month peaks changed over time. In the modelling exercises, U- and J-shaped exposure-risk relationships generate time series with both 6 and 12 month periodicities. Changing the weightings of the population exposure risks result in unexpected properties. A J-shaped exposure-risk relationship with a diminishing population exposure over time fitted the observed seasonal pattern in the Danish birth weight data. Conclusion In keeping with many other studies, Danish birth anthropometric data show complex and shifting seasonal patterns. We speculate that annual periodicities with non-linear exposure-risk models may underlie these findings. Understanding the nature of seasonal fluctuations can help generate candidate exposures.

Effects of extreme temperatures on years of life lost for cardiovascular deaths : a time series study in Brisbane, Australia

Background: Extreme temperatures are associated with cardiovascular disease (CVD) deaths. Previous studies have investigated the relative CVD mortality risk of temperature, but this risk is heavily influenced by deaths in frail elderly persons. To better estimate the burden of extreme temperatures we estimated their effects on years of life lost due to CVD. Methods and Results: The data were daily observations on weather and CVD mortality for Brisbane, Australia between 1996 and 2004. We estimated the association between daily mean temperature and years of life lost due to CVD, after adjusting for trend, season, day of the week, and humidity. To examine the non-linear and delayed effects of temperature, a distributed lag non-linear model was used. The model’s residuals were examined to investigate if there were any added effects due to cold spells and heat waves. The exposure-response curve between temperature and years of life lost was U-shaped, with the lowest years of life lost at 24 °C. The curve had a sharper rise at extremes of heat than of cold. The effect of cold peaked two days after exposure, whereas the greatest effect of heat occurred on the day of exposure. There were significantly added effects of heat waves on years of life lost. Conclusions: Increased years of life lost due to CVD are associated with both cold and hot temperatures. Research on specific interventions is needed to reduce temperature-related years of life lost from CVD deaths.

Learning hierarchical prototypes of motion time series for interactive systems

Abstract. For interactive systems, recognition, reproduction, and generalization of observed motion data are crucial for successful interaction. In this paper, we present a novel method for analysis of motion data that we refer to as K-OMM-trees. K-OMM-trees combine Ordered Means Models (OMMs) a model-based machine learning approach for time series with an hierarchical analysis technique for very large data sets, the K-tree algorithm. The proposed K-OMM-trees enable unsupervised prototype extraction of motion time series data with hierarchical data representation. After introducing the algorithmic details, we apply the proposed method to a gesture data set that includes substantial inter-class variations. Results from our studies show that K-OMM-trees are able to substantially increase the recognition performance and to learn an inherent data hierarchy with meaningful gesture abstractions.

Spatiotemporal model or time series model for assessing city-wide temperature effects on mortality?

Most studies examining the temperature–mortality association in a city used temperatures from one site or the average from a network of sites. This may cause measurement error as temperature varies across a city due to effects such as urban heat islands. We examined whether spatiotemporal models using spatially resolved temperatures produced different associations between temperature and mortality compared with time series models that used non-spatial temperatures. We obtained daily mortality data in 163 areas across Brisbane city, Australia from 2000 to 2004. We used ordinary kriging to interpolate spatial temperature variation across the city based on 19 monitoring sites. We used a spatiotemporal model to examine the impact of spatially resolved temperatures on mortality. Also, we used a time series model to examine non-spatial temperatures using a single site and the average temperature from three sites. We used squared Pearson scaled residuals to compare model fit. We found that kriged temperatures were consistent with observed temperatures. Spatiotemporal models using kriged temperature data yielded slightly better model fit than time series models using a single site or the average of three sites' data. Despite this better fit, spatiotemporal and time series models produced similar associations between temperature and mortality. In conclusion, time series models using non-spatial temperatures were equally good at estimating the city-wide association between temperature and mortality as spatiotemporal models.

Sunshine, rainfall, humidity and child pneumonia in the tropics : time-series analyses

Few studies have formally examined the relationship between meteorological factors and the incidence of child pneumonia in the tropics, despite the fact that most child pneumonia deaths occur there. We examined the association between four meteorological exposures (rainy days, sunshine, relative humidity, temperature) and the incidence of clinical pneumonia in young children in the Philippines using three time-series methods: correlation of seasonal patterns, distributed lag regression, and case-crossover. Lack of sunshine was most strongly associated with pneumonia in both lagged regression [overall relative risk over the following 60 days for a 1-h increase in sunshine per day was 0·67 (95% confidence interval (CI) 0·51–0·87)] and case-crossover analysis [odds ratio for a 1-h increase in mean daily sunshine 8–14 days earlier was 0·95 (95% CI 0·91–1·00)]. This association is well known in temperate settings but has not been noted previously in the tropics. Further research to assess causality is needed.