Pleural anthracosis as an indicator of lifetime exposure to urban air pollution: An autopsy-based study in Sao Paulo.

Many studies have been conducted to evaluate the association between air pollution and adverse health effects using a wide variety of methods to assess exposure. However, the assessment of individual long-term exposure to ambient air pollution is a challenging task and has not been evaluated in a large autopsy study. Our goal was to investigate whether exposure to urban air pollution is associated to the degree of lung anthracosis, considering modifying factors such as personal habits, mobility patterns and occupational activities. We conducted a study in Sao Paulo, Brazil from February 2017 to June 2018, combining epidemiological, spatial analysis and autopsy-based approaches. Information about residential address, socio-demographic details, occupation, smoking status, time of residence in the city and time spent commuting was collected via questionnaires applied to the next-of-kin. Images of the pleura surface from upper and lower lobes were used to quantify anthracosis in the lungs. We used multiple regression models to assess the association between the amount of carbon deposits in human lungs, measured by the fraction of pleural anthracosis (FA), and potential explanatory variables. We analyzed 413 cases and our data showed that for each additional hour spent in daily commuting, the ratio FA/(1-FA) is multiplied by 1.05 (95% confidence interval: [1.02; 1.08]). The estimated coefficient for daily hours spent in traffic was not considerably affected by the inclusion of socio-demographic variables and smoking habits. We estimate a tobacco equivalent dose of 5 cigarettes per day in a city where annual PM2.5 concentration oscillates around 25 µg/m3. Pleural anthracosis is a potential index of lifetime exposure to traffic-derived air pollution.

Exposure to fine particles increases blood pressure of hypertensive outdoor workers: A panel study.

BACKGROUND: Hypertension and air pollution are two important risk factors for cardiovascular morbidity and mortality. Although several studies suggest that air pollution has a significant impact on blood pressure, studies on long-term effects are sparse and still controversial. OBJECTIVE: To evaluate the effects of exposure of outdoor workers to different levels of traffic-generated PM2.5 on blood pressure. DESIGN: This is an observational panel study. PARTICIPANTS: 88 non-smoking workers exposed to different concentrations of air pollution were evaluated weekly along four successive weeks. MEASUREMENTS: In each week, personal monitoring of 24-h PM2.5 concentration and 24-h ambulatory blood pressure were measured. The association between blood pressure variables and PM2.5, adjusted for age, body mass index, time in job, daily work hours, diabetes, hypertension and cholesterol was assessed by means of multiple linear regression models fitted by least squares. RESULTS: Exposure to PM2.5 (ranging from 8.5 to 89.7 µg/m3) is significantly and consistently associated with an increase in average blood pressure. An elevation of 10 µg/m3 in the concentration of PM2.5 is associated with increments of 3.9 mm Hg (CI 95% = [1.5; 6.3]) in average systolic 24-h blood pressure for hypertensive and/or diabetic workers. CONCLUSION: Exposure to fine particles, predominantly from vehicular traffic, is associated with elevated blood pressure in hypertensive and/or diabetic workers.

Sample size for estimating the mean concentration of organisms in ballast water.

We consider the computation of sample sizes for estimating the mean concentration of organisms in ballast water. Given the possible heterogeneity of their distribution in the tank, we adopt a negative binomial model to obtain confidence intervals for the mean concentration. We show that the results obtained by Chen and Chen (2012) in a different set-up hold for the proposed model and use them to develop algorithms to compute sample sizes both in cases where the mean concentration is known to lie in some bounded interval or where there is no information about its range. We also construct simple diagrams that may be easily employed to decide for compliance with the D-2 regulation of the International Maritime Organization (IMO).

Competing regression models for longitudinal data.

The choice of an appropriate family of linear models for the analysis of longitudinal data is often a matter of concern for practitioners. To attenuate such difficulties, we discuss some issues that emerge when analyzing this type of data via a practical example involving pretest-posttest longitudinal data. In particular, we consider log-normal linear mixed models (LNLMM), generalized linear mixed models (GLMM), and models based on generalized estimating equations (GEE). We show how some special features of the data, like a nonconstant coefficient of variation, may be handled in the three approaches and evaluate their performance with respect to the magnitude of standard errors of interpretable and comparable parameters. We also show how different diagnostic tools may be employed to identify outliers and comment on available software. We conclude by noting that the results are similar, but that GEE-based models may be preferable when the goal is to compare the marginal expected responses.

Design-based random permutation models with auxiliary information¶

We extend the random permutation model to obtain the best linear unbiased estimator of a finite population mean accounting for auxiliary variables under simple random sampling without replacement (SRS) or stratified SRS. The proposed method provides a systematic design-based justification for well-known results involving common estimators derived under minimal assumptions that do not require specification of a functional relationship between the response and the auxiliary variables.

Prediction with measurement errors in finite populations.

We address the problem of selecting the best linear unbiased predictor (BLUP) of the latent value (e.g., serum glucose fasting level) of sample subjects with heteroskedastic measurement errors. Using a simple example, we compare the usual mixed model BLUP to a similar predictor based on a mixed model framed in a finite population (FPMM) setup with two sources of variability, the first of which corresponds to simple random sampling and the second, to heteroskedastic measurement errors. Under this last approach, we show that when measurement errors are subject-specific, the BLUP shrinkage constants are based on a pooled measurement error variance as opposed to the individual ones generally considered for the usual mixed model BLUP. In contrast, when the heteroskedastic measurement errors are measurement condition-specific, the FPMM BLUP involves different shrinkage constants. We also show that in this setup, when measurement errors are subject-specific, the usual mixed model predictor is biased but has a smaller mean squared error than the FPMM BLUP which point to some difficulties in the interpretation of such predictors.

Random changepoint segmented regression with smooth transition.

We consider random changepoint segmented regression models to analyse data from a study conducted to verify whether treatment with stem cells may delay the onset of a symptom of amyotrophic lateral sclerosis in genetically modified mice. The proposed models capture the biological aspects of the data, accommodating a smooth transition between the periods with and without symptoms. An additional changepoint is considered to avoid negative predicted responses. Given the nonlinear nature of the model, we propose an algorithm to estimate the fixed parameters and to predict the random effects by fitting linear mixed models iteratively via standard software. We compare the variances obtained in the final step with bootstrapped and robust ones.

Psychological characteristics are associated with healthcare worker adherence to infection control practices.

BACKGROUND: Most bloodstream infections related to vascular catheters can be avoided if evidence-based practices are applied during insertion and maintenance. In practice, adherence by health care workers (HCWs) is unsatisfactory and is the main current challenge. The objective of this study is to investigate associations between adherence to infection control practices and performance in psychological tests. METHODS: We conducted a prospective observational study in 4 intensive care units involving HCWs. Physicians were observed for adherence to hand hygiene (HH). Nurses were observed during central venous catheter dressing and handling. HCWs were then evaluated psychologically. RESULTS: There were 7,572 observations of 248 HCWs. Adherence to different steps of central venous catheter manipulation ranged widely: from 13% for HH before procedure to 95% regarding the use of gloves. Adherence to HH ranged from 14% before to 99% after dressing. For physicians, HH ranged from 10% before touching patients to 98% after touching body fluids, and adherence was associated with age, self-esteem, and aggression. For nurses, adherence was positively associated with deference, and negatively associated with nurturance. CONCLUSIONS: Psychosocial variables affect the quality of care that HCWs provide. The next step would be to define what type of psychological interventions could be effective.

Spatial-temporal variability of metal pollution across an industrial district, evidencing the environmental inequality in São Paulo.

Although air pollution decreased in some cities that shifted from an industrial to a service-based economy, and vehicular emission regulation became more restrictive, it is still a major risk factor for mortality worldwide. In central São Paulo, Brazil, air quality monitoring stations and tree-ring analyses revealed a decreasing trend in the concentrations of particulate matter and metals. Such trends, however, may not be observed in industrial districts located in the urban periphery, where the usual mobile sources may be combined with local stationary sources. To evaluate environmental pollution in an industrial district in southeastern São Paulo, we assessed its spatial variability, by measuring magnetic properties and concentrations of Al, Ba, Ca, Cl, Cu, Fe, K, Mg, Mn, P, S, Sr, Zn in the bark of 62 trees, and its temporal trends, by measuring Cd, Cu, Ni, Pb, V, Zn in tree rings of three trees. Source apportionment analysis based on tree barks revealed two clusters with high concentrations of metals, one related to vehicular and industrial emissions (Al, Ba, Cu, Fe, Zn) in the east side of the industrial cluster, and the other related to soil resuspension (Cu, Zn, Mn) in its west side. These patterns are also supported by the magnetic properties of bark associated with iron oxides and titanium-iron alloy concentrations. Dendrochemical analyses revealed that only the concentrations of Pb consistently decreased over the last four decades. The concentrations of Cd, Cu, Ni, V, and Zn did not significantly decrease over time, in contrast with their negative trends previously reported in central São Paulo. This combined biomonitoring approach revealed spatial clusters of metal concentration in the vicinity of this industrial cluster and showed that the local population has not benefited from the decreasing polluting metal concentrations in the last decades.

Evaluation of the discrepancy between clinical diagnostic hypotheses and anatomopathological diagnoses resulting from autopsies.

OBJECTIVES: An objective of clinical autopsies is to determine the final cause of death and the pathological changes that may have triggered it. Despite advances in Medicine, the level of discrepancy between clinical and autopsy diagnoses remains significant. The aim of this study was to compare the data obtained from autopsies carried out at the São Bernardo do Campo/SP Death Verification Section with clinical diagnostic hypotheses proposed during medical care. METHOD: This was a retrospective study involving the comparison of necroscopic reports issued by the São Bernardo do Campo/São Paulo Death Verification Section in 2014 and 2015 and the Cadaver Referral Guides completed by attending physicians prior to the necroscopic examination. RESULTS: A total of 465 cases were analyzed. In general, discrepancies between the clinical diagnostic hypothesis and the autopsy diagnosis occurred in 28% of the cases. A logistic regression model, with diagnostic discrepancy as a response variable and sex, age, duration of care, type of institution providing medical care and organ system as explanatory variables, was fit to the data; the results indicated that all explanatory variables with the exception of organ system are not significant (p>0.132). CONCLUSIONS: Discrepancies between clinical diagnostic hypotheses and autopsy diagnoses continue to occur, despite new developments in complementary examinations and therapies. The odds of a discrepancy when patients present with diseases of the cardiac system are greater than those when there are problems in the vascular, endocrine and neurological systems.

The role of air pollution and climate on the growth of urban trees.

The urban environment features poor air quality and harsher climate conditions that affect the life in the cities. Citizens are especially vulnerable to climate change, because heat island and impervious exacerbates extreme climate events. Urban trees are important tools for mitigation and adaptation of cities to climate change because they provide ecosystem services that increase while trees grow. Nonetheless, the growth of trees may be affected by the harsher conditions found in the urban environment. We assessed the impact of air pollution and climate on the spatial/temporal variability of tree growth in São Paulo, Brazil, one of the largest urban conglomerates in the world. For this purpose, we sampled 41 trees of the Tipuana tipu species in a region that includes industrial areas. We built a tree-ring chronology using standard dendrochronological methods. Spatial analyses show that trees grow faster in the warmer parts of the city and under higher concentrations of airborne P, whereas growth is reduced under higher concentrations of Al, Ba, Zn. Particulate matter (PM10) from the industrial cluster also reduce average growth rate of trees, up to 37% in all diameter classes. Similar results were obtained via temporal analyses, suggesting that the annual growth rate is positively associated with temperature, which explain 16% of interannual growth variability. Precipitation, on the other hand, has no association with tree growth. The average concentration of PM10 explains 41% of interannual growth variability, and higher concentrations during the driest months reduce growth rate. Despite heat island effect and water limitation in the soil of the city, this species takes advantage of warmer conditions and it is not limited by water availability as measured by precipitation. On the other hand, air pollution directly impacts the growth of these trees being a major limiting growth factor.

Performance of Balanced Two-Stage Empirical Predictors of Realized Cluster Latent Values from Finite Populations: A Simulation Study.

Predictors of random effects are usually based on the popular mixed effects model developed under the assumption that the sample is obtained from a conceptual infinite population; such predictors are employed even when the actual population is finite. Two alternatives that incorporate the finite nature of the population are obtained from the superpopulation model proposed by Scott and Smith (1969, JASA, 64: 830-840) or from the finite population mixed model recently proposed by Stanek and Singer (2004, JASA, 99:1119-1130). Predictors derived under the latter model with the additional assumptions that all variance components are known and that within-cluster variances are equal have smaller mean squared error than the competitors based on either the mixed effects or Scott and Smith's models. As population variances are rarely known, we propose method of moment estimators to obtain empirical predictors and conduct a simulation study to evaluate their performance. The results suggest that the finite population mixed model empirical predictor is more stable than its competitors since, in terms of mean squared error, it is either the best or the second best and when second best, its performance lies within acceptable limits. When both cluster and unit intra-class correlation coefficients are very high (e.g., 0.95 or more), the performance of the empirical predictors derived under the three models is similar.

Predicting Random Effects with an Expanded Finite Population Mixed Model.

Prediction of random effects is an important problem with expanding applications. In the simplest context, the problem corresponds to prediction of the latent value (the mean) of a realized cluster selected via two-stage sampling. Recently, Stanek and Singer (JASA, 2004) developed best linear unbiased predictors (BLUP) under a finite population mixed model that outperform BLUPs from mixed models and superpopulation models. Their setup, however, does not allow for unequally sized clusters. To overcome this drawback, we consider an expanded finite population mixed model based on a larger set of random variables that span a higher dimensional space than those typically applied to such problems. We show that BLUPs for linear combinations of the realized cluster means derived under such a model have considerably smaller mean squared error (MSE) than those obtained from mixed models, superpopulation models, and finite population mixed models. We motivate our general approach by an example developed for two-stage cluster sampling and show that it faithfully captures the stochastic aspects of sampling in the problem. We also consider simulation studies to illustrate the increased accuracy of the BLUP obtained under the expanded finite population mixed model.

Simple linear regression with interval censored dependent and independent variables.

We consider a simple linear regression model that accommodates situations where both the dependent and the independent variables are interval censored. We obtain maximum likelihood estimators of its parameters and compare their performance with that of estimators derived under ordinary linear regression models. We also develop prediction intervals for the response and illustrate the results with data from an audiometric study designed to evaluate the possibility of prediction of behavioural thresholds from physiological thresholds.

Suicides by hanging and its association with meteorological conditions in São Paulo.

The main goal of this study was to evaluate the association between daily cases of hanging suicides and meteorological conditions in São Paulo, Brazil. We considered a retrospective observational study based on the analysis of all necroscopic medical-expert reports available in digital form from the central unit of the Instituto Médico Legal (Medical Legal Institute) of São Paulo between July 1, 2006 and June 31, 2007. The meteorological variables were combined via Principal Components Analysis. In order to explain their association with the frequency of suicides, Poisson regression models were employed. The analysis suggests that hotter and brighter days are associated with higher incidence of hanging suicides.

Tree rings reveal the reduction of Cd, Cu, Ni and Pb pollution in the central region of São Paulo, Brazil.

The concern about environmental pollution has risen in the last decades because of its effects on human's health. However, evaluation of the exposure to certain pollutants is currently hampered by the availability of past environmental data. Tree rings are an alternative to reconstruct environmental variability of pre-instrumental periods. Nevertheless, this approach has some reported limitations including migration of chemical elements in the tree rings. The aim of this study was to evaluate the distribution of Cd, Cu, Hg, Na, Ni, Pb, Zn in the tree rings of Tipuana tipu (Fabaceae) to aid the reconstruction of past environmental pollution. We sampled trees in the central region of the city of São Paulo, Brazil, and scanned their tree rings using LA-ICP-MS. We used these data to evaluate the temporal trends of chemical elements under investigation. Results show a non-random distribution of these chemical elements within the tree rings, with higher content in the cell-walls of vessels and lower content in the fibers. Sodium was the only element intimately related to the axial parenchyma cells. Due to differences in elemental composition of xylem cells, temporal trends where evaluated using distinct quartiles of data distribution in each tree ring. The first quartile represents the lower content found in fibers and parenchyma, while the third quartile corresponds to the higher content found in vessels. Data from vessels better represent the decreasing trend of Cd, Cu, Pb, and Ni in the last three decades. This reduction is less significant for Na and Zn. Our results highlight the potential to improve the records of environmental pollution using data from different cells. Pronounced reduction in Pb may be attributed to the lead phase-out in gasoline, while the decreasing trend of Cd, Cu, Ni pollution is probably related to increasing efficiency of vehicles and the deindustrialization of São Paulo. Chemical elements are non-randomly distributed in tree rings. Chemical content of vessels cell-walls is a reliable record of metal pollution, which is decreasing in São Paulo.

Pericytes Extend Survival of ALS SOD1 Mice and Induce the Expression of Antioxidant Enzymes in the Murine Model and in IPSCs Derived Neuronal Cells from an ALS Patient.

Amyotrophic Lateral Sclerosis (ALS) is one of the most common adult-onset motor neuron disease causing a progressive, rapid and irreversible degeneration of motor neurons in the cortex, brain stem and spinal cord. No effective treatment is available and cell therapy clinical trials are currently being tested in ALS affected patients. It is well known that in ALS patients, approximately 50% of pericytes from the spinal cord barrier are lost. In the central nervous system, pericytes act in the formation and maintenance of the blood-brain barrier, a natural defense that slows the progression of symptoms in neurodegenerative diseases. Here we evaluated, for the first time, the therapeutic effect of human pericytes in vivo in SOD1 mice and in vitro in motor neurons and other neuronal cells derived from one ALS patient. Pericytes and mesenchymal stromal cells (MSCs) were derived from the same adipose tissue sample and were administered to SOD1 mice intraperitoneally. The effect of the two treatments was compared. Treatment with pericytes extended significantly animals survival in SOD1 males, but not in females that usually have a milder phenotype with higher survival rates. No significant differences were observed in the survival of mice treated with MSCs. Gene expression analysis in brain and spinal cord of end-stage animals showed that treatment with pericytes can stimulate the host antioxidant system. Additionally, pericytes induced the expression of SOD1 and CAT in motor neurons and other neuronal cells derived from one ALS patient carrying a mutation in FUS. Overall, treatment with pericytes was more effective than treatment with MSCs. Our results encourage further investigations and suggest that pericytes may be a good option for ALS treatment in the future. Graphical Abstract ᅟ.

Influence of cavity dimensions and their derivatives (volume and 'C' factor) on shrinkage stress development and microleakage of composite restorations.

OBJECTIVES: To determine, in vitro, the influence of cavity dimensions on shrinkage stress development and microleakage of composite restorations. METHODS: Cylindrical cavities with 2, 3, 4 or 6 mm diameter and 1 or 2 mm depth were prepared in bovine incisors (with enamel margins) and reproduced in photoelastic resin. Cavities were restored in bulk (Single Bond+Filtek Z250). Stress fringes were analyzed 10 min after photoactivation. Restored teeth were stored for 24 h, coated with nail polish and immersed in 50% AgNO3 for 2 h, followed by 6 h in developing solution. Specimens were sectioned twice and microleakage was measured under 20x magnification. Photoelastic data were analyzed descriptively only, due to lack of variability in some groups. Microleakage was analyzed through (generalized linear) regression models. Pearson correlation coefficients were computed to evaluate the relationship between microleakage and 'C' factor or volume. RESULTS: Fringe order was higher at the internal angles than at the margins of the restorations. There was a trend for higher fringe orders with increasing diameter and depths. Regression analysis revealed a significant influence of restoration depth for diameters above 2mm. The effect of diameter on microleakage is significantly higher (p < 0.0001) for 2-mm deep restorations, compared to those 1-mm deep. Pearson correlation coefficients suggest some relationship between microleakage and volume (r = 0.724, p < 0.0001), but not between microleakage and 'C' factor (r = 0.048, p = 0.6120). CONCLUSIONS: Shrinkage stress and microleakage were higher in restorations with larger diameters and depths. Microleakage seemed to be related to a restoration's volume, but not to its 'C' factor.

Overt Primary Hypothyroidism in an Industrial Area in São Paulo, Brazil: The Impact of Public Disclosure.

Background: Primary hypothyroidism (PH) is the most common thyroid pathology. Purpose: to evaluate the impact of public disclosure of an unexpected number of PH cases on the frequency of patients seeking medical evaluation for endocrinological diseases. Methods: data on 6306 subjects (3356 living in the surroundings of a petrochemical complex and 2950 in a control region) were collected over a 15-year time span. Thyroid function was determined by serum levels of triiodothyronine, thyroxine, free thyroxine and thyrotrophin. Antithyroglobulin and antithyroperoxidase antibodies and sonographic scans of the thyroid were performed in all patients. The data were analyzed via log-linear models to compute odds and odds ratios. Results: An increasing trend in the odds of PH was detected along the observation period with greater slope in the study region than in the control region. The odds of PH in the post-disclosure period (2002 to 2004) are greater than the corresponding ones in the pre-disclosure period (1989 to 2001). Conclusions: This study shows that living in the surroundings of a petrochemical complex may be an important risk factor for PH for both adults and children. Furthermore, public disclosure of such risk factor contributes to the awareness of the problem and to the possibility of an early diagnosis.

[Echocardiographic post-neonatal progress of preterm neonates with patent ductus arteriosus]. / Evolução ecocardiográfica de recém-nascidos com persistência do canal arterial.

OBJECTIVE: To identify clinical and echocardiography predictors of the spontaneous closure of patent ductus arteriosus in preterm neonates. METHODS: Sixty-one consecutive preterm neonates (gestational age 30+/-2 weeks, birth weight 1.2+/-0.2 kg) were evaluated by echocardiogram on their third day of life and those with patent ductus arteriosus were selected for a prospective cohort. Echocardiography was repeated weekly until they reached term. Based on their progress, the sample population was divided into two groups, depending on whether spontaneous closure of patent ductus arteriosus took place (Group A) or not (Group B). The prevalence of clinical signs of patent ductus arteriosus and echocardiography findings at baseline were compared between the groups. RESULTS: Patent ductus arteriosus was found in 21 neonates (34%). Spontaneous closure was observed during follow-up of seven patients (Group A, 33% of those with patent ductus arteriosus), in contrast with the remaining 14 patients (Group B, 67%). Clinical signs of patent ductus arteriosus were present in 14% of the patients in Group A, compared with 71% in group B (p = 0.01). At baseline, Group B had a larger ductus diameter in relation to Group A (2.6+/-0.6 mm vs. 1.4+/-0.6 mm; p = 0.003). The area under the ROC curve in relation to ductus diameter was 0.93 (p = 0.003) and 100% sensitivity for identifying cases without spontaneous closure was obtained at the cutoff point of 1.7 mm, while 100% specificity was observed taking 2.2 mm as the cutoff. CONCLUSIONS: In preterm neonates, a patent ductus arteriosus greater than 2.2 mm on the third day of life predicts no spontaneous closure and suggests a need for early treatment, especially when associated with clinical signs.