Thèses sur le sujet « Correlated Exposure »

Thesis: S.M. in Management Studies, Massachusetts Institute of Technology, Sloan School of Management, 2014.
Cataloged from PDF version of thesis.
Includes bibliographical references (page 62).
It is very hard to identify and evaluate very early stage investment opportunities in disruptive digital consumer-facing startups as they usually don't have any meaningful revenue data yet. However, these growing startups have "momentums". In classical mechanics, momentum is the product between mass and velocity. When it comes to startups, we can see revenue and web traffic as the mass and unique page views, social presence and sentiment, page rank, inbound links... as velocity (cf. Danielle Morrill start ups momentum index). Analyzing all these data is usually the most relevant way for investors to evaluate investment opportunities. It is however very unclear to what extent startups momentum is an indicator of financial performance. I would like to focus on social media exposure as an indicator of velocity for startups, and investigate further the correlations between social media exposure and revenue data.
by Solene Genre.
S.M. in Management Studies

La ricerca epidemiologica mira a generare una migliore comprensione dei meccanismi sanitari e dell'eziologia della malattia. L'abbondanza di informazioni raccolte tramite cartelle cliniche elettroniche ha generato un problema di Big Data, rendendo l'identificazione di modelli predittivi dei rischi per la salute e dei possibili outcome climici ancora più complessa. Pertanto, sono aumentati in importanza e popolarità gli approcci statistici di selezione delle variabili. Tuttavia, i metodi di selezione delle variabili ancora oggi più utilizzati in epidemiologia si basano su conoscenze pregresse o utilizzano approcci automatizzati (es. regressione Stepwise). Quando però si combinano contemporaneamente più variabili d’esposizione con una complessa struttura di correlazione e con potenziali relazioni di tipo non lineare e non additive con l’outcome studiato, questi approcci risultano limitati nel tenere conto della multicollinearità. In questo contesto vengono utilizzati metodi di regressione penalizzati, come il least absolute shrinkage and selection operator (LASSO) e le sue numerose varianti, ma ricerche recenti hanno evidenziato che funzionano male quando sussiste un qualche tipo di struttura complessa di dipendenza tra le covariate. Negli ultimi anni, sono stati sviluppati metodi di selezione delle variabili appartenenti al framework Bayesiano, capaci di gestire congiuntamente più predittori, anche altamente correlati tra loro e con legami non lineari e non additivi con l’outcome. Tra questi metodi Bayesiani spiccano quelli che utilizzano priori spike-and-slab o priori shrinkage. Questi metodi sono ora ampiamente studiati e impiegati all'interno della letteratura epidemiologica ambientale e clinica. In questo lavoro abbiamo considerato e confrontato tre modelli di selezione delle variabili di tipo Bayesiano: il Bayesian kernel machine regression (BKMR), il Bayesian semiparametric regression (BSR) e il Bayesian LASSO (BLASSO). Il BKMR modellizza le associazioni tra predittori e outcome attraverso l'uso di una funzione kernel dei predittori, il BSR utilizzando spline naturali, mentre il BLASSO attraverso una funzione lineare dei predittori, considerando un parametro di shrinkage che mira ad effettuare selezione delle variabili ponendo a zero il coefficiente di regressione. In primo luogo, abbiamo valutato la bontà di adattamento e la capacità di selezione dei modelli attraverso uno studio di simulazione, generando diversi scenari con complessa struttura di correlazione e con relazioni disparate tra predittori e outcome. Successivamente, sulla base dei risultati ottenuti nelle simulazioni, abbiamo applicato questi metodi a due casi di studio reali. Il primo è lo studio ROCAV (Rischio di malattie cardiovascolari e aneurisma dell'aorta addominale a Varese), in collaborazione con l'Università dell'Insubria di Varese, con l'obiettivo di studiare l'impatto dell'esposizione a lungo termine a inquinanti ambientali con funzione respiratoria valutata mediante spirometria. I risultati hanno mostrato come non ci sia un inquinante che predomini sugli altri in termini di effetto, ma che tutti contribuiscono all’impatto sulla funzionalità respiratoria. Nel secondo studio (Follow Up OBese patients at AUXOlogico institute (FUOBAUXO)), in collaborazione con l'Istituto Auxologico Italiano, abbiamo studiato la relazione tra variabili antropometriche, cliniche, biochimiche, infiammatorie e metaboliche sulla perdita di peso percentuale in pazienti affetti da obesità in un periodo di ospedalizzazione di 40 giorni. Il risultato di questo lavoro ha portato all'individuazione di subsets di variabili potenzialmente associate con l’outcome di perdita di peso per diverse tipologie di paziente in base all’età, il genere e livello di BMI.
Epidemiological research aims to generate a better understanding of the health mechanisms and disease etiology. Nowadays, the abundance of clinical information collected via electronic medical records have made high-dimensional data extremely popular and the identification of predictive modeling of health risks and possible outcomes has become even more challenging. Therefore, many variable selection approaches have increased in importance and popularity. Nevertheless, the most frequently variable selection methods still used in epidemiology are based on prior knowledge or using stepwise automated selection approaches. However, when multiple exposures co-occur and have a strong complex correlation structure, traditional statistical approaches are limited in accounting for multi-collinearity or standard error inflation. To reduce this problem, dimensionality reduction methods –such as principal component and factor analyses– are very valuable. However, those approaches focus on the transformation of the original variables thus leading to an interpretability issue. In addition, multiple co-occurring predictors can have non-linear and non-additive relationships with the health outcome and most of the statistical methods fail to model properly those relationships. Penalized regression methods are used in this context, such as least absolute shrinkage and selection operator (LASSO) and its numerous variants, but recent research highlighted that they perform poorly when there exists some type of dependence structure between the covariates. In recent years, Bayesian variable selection methods have been developed to handle jointly multiple correlated predictors and both non-linear and non-additive relationships, allowing the inclusion of prior information. Among these Bayesian methods stand out those employing spike-and-slab priors or shrinkage priors for features selection. These methods are now widely studied and employed within the environmental and clinical epidemiological literature. In this thesis work, we considered and compared three Bayesian variable selection models: the Bayesian kernel machine regression (BKMR), the Bayesian semiparametric regression (BSR) and the Bayesian LASSO (BLASSO). BKMR models the outcome-predictors associations using a kernel function of predictors, BSR employing natural splines, while BLASSO using a linear function of predictors and considering a shrinkage parameter that aims to perform variable selection by setting the regression coefficient to zero. We firstly evaluated the models’ goodness of fit and selection ability simulating several predictors with a complex correlation structure and with disparate relationships with a continuous outcome, considering data with different sample sizes. Subsequently, based on the results obtained in the simulations we applied this methods to two real case studies. The first is the ROCAV study (Risk Of Cardiovascular diseases and abdominal aortic Aneurism in Varese), in collaboration with the University of Insubria of Varese, with the aim of studying the impact of long-term exposure to environmental pollutants with respiratory function assessed by spirometry. Results showed that no pollutant overcome the others in terms of effect, but rather all may contribute to the relationship with the respiratory outcome. The second, in collaboration with the Italian Auxological Institute, leveraged data on weight loss in hospitalized obesity affected women from the Follow Up OBese patients at AUXOlogico institute (FUOBAUXO) cohort, with the aim to select most important predictors in explaining the association between biochemical, anthropometric and clinical variables on weight loss percentage in these patients over a period of 40 days. The result of this work led to the identification of subsets of variables potentially associated with the weight loss outcome for different types of patients based on age, gender and BMI level.

First Nations peoples experience many benefits from eating locally-harvested wild foods, but these benefits must be considered along with the potential risks associated with exposure to environmental contaminants. Unlike store-bought foods, wild foods are an important traditional resource and a significant source of dietary protein, essential minerals and polyunsaturated fatty acids, believed to help in the prevention and treatment of obesity and obesity-related diseases such as type-2 diabetes mellitus. Wild foods continue to be an important and healthy food choice for First Nations peoples; however, they are also a primary source of dietary mercury, polychlorinated biphenyls (PCBs) and other persistent organic pollutants (POPs). To assess the effects of wild food consumption on dietary markers and contaminant accumulation, we grouped individuals from two remote Oji-Cree First Nations communities of north-western Ontario (n=71) according to their level of wild food consumption. In this study, I observed significantly higher organic contaminants in blood and higher mercury concentrations in hair for individuals consuming greater amounts of wild food. Age-adjusted contaminant concentrations were on average 3.5-times higher among high-frequency wild food consumers, with many exceeding federal and international health guidelines for mercury and PCB exposures. Contaminants in these populations approach, and in some cases exceed, threshold levels for adverse effects with potential consequences especially for prenatal development. Here, I also investigated the potential for stable isotope ratios of carbon and nitrogen (δ13C and δ15N) to serve as dietary markers and found strong positive correlations between stable isotopes and frequency of wild food and fish consumption. Frequency of fish consumption and δ15N was also shown to be positively correlated with mercury concentrations in hair and PCB concentrations in plasma. The results of this thesis demonstrate that known differences in dietary behaviour are clearly reflected in stable isotope ratios and contaminant concentrations. The data also show that contaminant exposures to those consuming wild foods in remote Boreal ecosystems is comparable to those associated with serious health effects in industrialized areas, and the problem of contaminants in wild foods is more widespread than the available literature would have led us to believe. These results affect our appreciation of contaminant exposures to First Nations peoples and will have implications for dietary choices, particularly if individuals are encouraged to consume greater amounts of wild foods for their proposed health benefits. We recommend further attention be given to the risks of contaminants in locally-harvested wild foods when promoting the benefits of their consumption to First Nations people as the problem of contaminants in remote communities practicing traditional lifestyles is often underreported and underplayed.

The etiology of musculoskeletal outcomes associated with the use of information technology (IT) has predominately been defined by studies of adults in their work environments. Theories explaining the causation of work related musculoskeletal disorders have identified individual user (biomechanical, physiological and psychosocial), task demand, work organization and environmental risk factors. Models based on these theories have subsequently been developed to investigate the causal relationship between IT exposure and outcomes experienced by the user.Computers are an important IT type used by children, and computer use by children is rapidly growing in both school and home environments. Recent literature demonstrates an increase in children’s reports of computer related musculoskeletal outcomes. Children’s computer use appears to be different to adult’s work related computer use. Thus, although many potential risk factors for children may be similar to those for adults, it is proposed that risk factors and models of causal relationships between computer use and musculoskeletal outcomes may vary for children.The main aims of this study were: (1) to investigate children’s computer exposure in their usual occupational environments of school and home; and (2) to develop and test a multivariable model that would assist in understanding relationships between child user correlates, computer exposure and computer related musculoskeletal outcomes.1351 students (792 boys and 559 girls) from eight primary and five secondary schools in Perth, Australia, participated in the study in 2006. Convenience sampling was undertaken within stratified groups, to ensure the sample had the required range of participants from different socioeconomic status (SES) backgrounds, both genders and school Years 1, 6, 9 and 11(approximate ages 6, 9, 14 and 16 years).The study design was cross sectional involving the completion of a questionnaire survey by participants, and for younger participants their parents. Questionnaires contained items relating to the participant and their activity exposure as an individual, within a family context, and within their neighbourhood. Physical measures of height and weight were also collected.The results showed that 100% of children had access to computers at school, and at home 98.9% of children had access to computers, with 95.9% reporting home internet access. The use of different exposure measures demonstrated that at school 97.8% of children had used a computer in the last month, for an average of 2.4 hours per week, commonly for 30-60 minutes in one sitting. At home 95.7% of children had used a computer in the last month, for an average of 7.2 hours per week, commonly for 60 - 120 minutes in one sitting. Computer activities performed more frequently at school were surfing the internet, learning programs and multimedia. At home the most frequent computer activities were surfing the internet and email. Children with bedroom computer access were found to have nearly 50% greater mean weekly hours of use. The use of a range of computer exposure measures (frequency, usual and longest duration, mean weekly hours and frequency of computer activities) provided better characterization of the amount and nature of children’s school and home computer exposure.Age and gender were associated with children’s school and home computer use. Computer use was greater with age for both boys and girls, and boys had greater use than girls across all Year levels for all exposure measures except school usual duration. Children with greater computer exposure were shown to experience less computer anxiety; reported more somatic complaints; had used a broader range of computer activities; had greater exposure to other IT activities (electronic games, TV, mobile phone) and moderate vigorous physical activity. SES was associated with computer exposure, with children from low SES backgrounds having greater home computer exposure, and children from high SES backgrounds having greater school computer exposure.Computer related musculoskeletal outcomes were reported by 10% of children for school computer use and 20% for home computers. The most commonly affected body locations were the neck and back, and 30% of those children reporting outcomes limited their activity participation, 10% took medication and 7% consulted a treating health professional. The use of a range of outcome measures allowed for a better understanding of the impact of children’s computer related musculoskeletal outcomes.Given the significant findings of different relationships between children’s computer exposure patterns at school and home, two models were developed and tested, with one model for school computer exposure and one model for home computer exposure. Path analysis modeling, accounting for user correlates, tested direct relationships and indirect relationships via computer exposure for a range of user correlates. The final school computer exposure model showed direct relationships between gender, somatic complaints, computer exposure and musculoskeletal soreness; and indirect relationships, via computer exposure, between age, computer flow, TV exposure, SES and musculoskeletal soreness. The final home computer exposure model showed direct relationships between gender, age, somatic complaints, computer exposure and musculoskeletal soreness; and indirect relationships, via computer exposure, between age, computer flow, computer anxiety, TV exposure, SES and musculoskeletal soreness.In conclusion, the child specific model tested within this study demonstrated direct relationships between children’s computer exposure and musculoskeletal outcomes. Additionally, direct and indirect relationships were also shown between a range of user correlates, the environment and musculoskeletal outcomes. These findings will assist researchers, teachers and parents to understand the range of potential risk factors for computer related musculoskeletal outcomes. This will also allow researchers to target interventions to child users and their computer environments to ensure children’s computer use is performed in a safe and productive manner.

The fetus is highly responsive to the level of glucocorticoids in the gestational environment. Perturbing glucocorticoids during fetal development could yield long-term consequences. Extending prior research about effects of prenatally exposed synthetic glucocorticoids (sGC) on brain structural development during childhood, we investigated functional brain correlates of cognitive conflict monitoring in term-born adolescents, who were prenatally exposed to sGC. Relative to the comparison group, behavioral response consistency (indexed by lower reaction time variability) and a brain correlate of conflict monitoring (the N2 event-related potential) were reduced in the sGC exposed group. Relatedly, source localization analyses showed that activations in the fronto-parietal network, most notably in the cingulate cortex and precuneus, were also attenuated in these adolescents. These regions are known to subserve conflict detection and response inhibition as well as top-down regulation of stress responses. Moreover, source activation in the anterior cingulate cortex correlated negatively with reaction time variability, whereas activation in the precuneus correlated positively with salivary cortisol reactivity to social stress in the sGC exposed group. Taken together, findings of this study indicate that prenatal exposure to sGC yields lasting impacts on the development of fronto-parietal brain functions during adolescence, affecting multiple facets of adaptive cognitive and behavioral control.

Thesis (Ph.D.)--George Mason University, 2009.
Vita: p. 118. Thesis director: Robert F. Smith. Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Psychology. Title from PDF t.p. (viewed June 10, 2009\). Includes bibliographical references (p. 101-117). Also issued in print.

Since 2004, herbal mixtures broadly known as Spice/K2, containing synthetic cannabinoids (SC) such as JWH-018, have been marketed as a legal marijuana surrogate. Previous studies of our group showed that JWH-018 has CB1-receptor dependent reinforcing properties and increases dopamine (DA) transmission selectively in the shell of the nucleus accumbens (NAc) at the dose of 0.25 mg/kg i.p. (De Luca et al., 2015). Other studies showed that taste stimuli increase extracellular DA in the NAc and in the medial prefrontal cortex (mPFC) of rats; this effect shows single-trial habituation in NAc shell but not in core or in mPFC (Bassareo et al., 2002). However, the selective disruption of mPFC by 6-OHDA lesions, abolishes habituation of DA responsiveness to taste stimuli in NAc shell (Bimpisidis et al., 2013). Such findings support the hypothesis of an inhibitory influence of mPFC on NAc DA, suggesting a top-down control of NAc DA by mPFC and its putative role in the loss of control of the motivational value of stimuli and in impulsivity (De Luca, 2014). In order to test if the repeated administration of JWH-018 is able to modulate the activity of DA terminal areas and is associated to changes in the responsiveness to motivational taste stimuli, adult male Sprague Dawley (SD) rats were administered once a day for 14 consecutive days with JWH-018 (0.25 mg/kg i.p.) or with vehicle. During the last day of administration, DA was quantified by in vivo brain microdialysis in the NAc and in the mPFC. JWH-018 repeated exposure decreases the sensitivity of NAc shell DA to the last JWH-018 administration. After a week of washout, DA was quantified in NAc shell, NAc core and mPFC of rats either naive or pre-exposed to chocolate (1 ml/5 min i.o.). JWH-018 administration decreases the sensitivity of NAc shell DA in naive rats, abolished habituation of DA responsiveness to repeated chocolate exposure in the NAc shell while induced it in the mPFC, suggesting a possible loss of control of the motivational value of stimuli. In the NAc core, JWH-018 treatment potentiated, delayed and prolonged the stimulatory DA response to taste stimuli of animals pre-exposed to chocolate. Parallel studies showed that repeated JWH-018 exposure reduces either spontaneous activity or number of VTA DA neurons, together with an increase of obsessive-compulsive/anxious behavior, attentional deficits, and signs of withdrawal. These data show that JWH-018 is able to change the activity of DA neurons and to induce differential adaptive changes of the responsiveness of DA transmission to taste stimuli in DA terminal areas, similarly to previous results obtained in mPFC 6-OHDA lesioned rats. Interestingly, these neurochemical and behavioral observation are associated with a neuroinflammatory phenotype, as indicated by IBA-1 immunoreactivity and reactive astrogliosis (GFAP) in DA brain areas. Therefore, JWH-018 induces behavioral effects and changes of glial cells (astrocytes and microglia), which might be related to the central effects observed after repeated JWH-018 administration. Taken together these results suggest that JWH-018 repeated treatment may reflect a model of addiction, and this study could be useful to understand if dysfunctions of cortical-limbic-striatal DA circuit, as well as glial cells alterations, can lead or are related to specific detrimental effects of recurring use of Spice/K2 drugs.

碩士
國立陽明大學
環境與職業衛生研究所
104
In recent years, researches have shown that the emitting pollutant from incinerator caused health effects of residents living near community. Meanwhile, workers in incinerator has more likelihood exposure to high levels of pollutants, such dioxin, various metals and polyaromatic hydrocarbon (PAH) etc. The objective of this study is to explore the association between levels of PAH metabolites in urine and oxidative stress. Total of 83 participants from employees in an incinerator, workplace of staffs nearly connected with incinerator plant, and residents living in the vicinity of the incinerator. Each participant was interviewed by a structured questionnaire and collected two urine specimens during pre-shift and post-shift. Urinary1-OHP (1-hydroxypyrene) and 3-OHBaP (3- hydroxybenzo (a) pyrene), respectively represent exposure to pyrene (Pyr) and benzo (a) pyrene (BaP),were analyzed by HPLC-Fluorescence and use the nonparametric statistics analysis. After adjusting for age, gender,educational level,smoke, incense, the result of multiple logistic regression showed that urinary 1-OHP level in high exposure group (HEG) was significantly higher in low exposure group (LEG)(p=0.01) .Similarly, urinary 3-OHP levels in HEG were significantly higher in LEG(p=0.02). Generally speaking, 3-OHBaP levels in urine were considerably higher in post-shift period, but not found in urinary 1-OHP levels. After adjusting for age, gender,educational level,smoke, incense, the result of multiple logistic regression showed that urinary PAH metabolites level was significantly related to MDA concentration , meaning urinary MDA levels affected by PAH exposures. Meanwhile, urinary PAHs metabolite levels also affected by smoking and use of personal protective equipment. We concluded workers in the incinerator showed high levels of PAH metabolites in urine exposure due to exposure to PAH in workplace. As a consequence, it is ii necessary to alleviate the emission of PAH from various processes in incinerator and to effectively reduce risk of PAH exposure by installing isolation area and by monitoring workers worn personal protective equipment.

碩士
國立陽明大學
環境與職業衛生研究所
100
Background and objective Air contaminated with various pollutants in urban and rural areas can cause long-term or short-term health effects. Recently, governments throughout the world have begun to pay attention to the association between the fine suspended particles PM2.5 and human health effects. In 2005, daily levels of PM2.5 particles have been included in the air quality monitoring stations in Taiwan. However, few studies have shown the associations between daily exposure to PM2.5 level and hospital admissions due to respiratory diseases. The objective of this study is to investigate the correlation between exposure to PM10 and PM2.5 levels and hospital admissions due to respiratory diseases in an urban area (Changhua City) and a rural area (Siansi Township). Materials and methods Data regarding hospital admissions due to respiratory diseases were obtained from Taiwan’s National Health Insurance Research. Daily PM10 level, PM2.5 level and temperature data were measured by Taiwan’s air quality monitoring station of the Environmental Protection Administration in Changhua City and in Siansi county during the period of 2000 to 2008. The software of SPSS 17 was used to create a generalized linear model to assess the correlation between daily hospital admissions for respiratory diseases and levels of PM10 and PM2.5. We created two models: a one-pollutant model and a two-pollutant model, both controlling for calendar years and temperature difference in the urban and rural areas for the 10-year period from 1999 through 2008. Results Based on two models, we found hospital admissions rates of respiratory diseases significantly increased with exposure to PM10 and PM2.5 level in the urban and rural areas. People living in Changhua city showed hospital admissions due to respiratory diseases being higher than those of residents living in Siansi county. Residents in the urban area exposed to PM10 and PM2.5, suffered from respiratory diseases at a rate of about two-folds higher than those of exposed residents in the rural area. This can be explained by the fact that residents have different levels of accessibility and utilization of health care services depending on whether they live in a rural or urban area. Conclusion We suggest environmental protection agencies set up guidelines or standards for air pollutants. They should pay attention to the relevant problems, including the uneven distribution and accessibility of health care services in urban and rural areas.

碩士
國立清華大學
生醫工程與環境科學系
104
Heavy metals exist ubiquitously in the living environment, and are very stable to accumulate in the food chain. Human are exposed to heavy metals by means of food, air and water. In recent years, there happened food safety scandals in Taiwan. The kitchen waste or gutter oil were recovered and refined by unscrupulous vendors, and sold to food stalls and restaurants. Diner-out has more chances to expose the heavy metals remained in the inferior oil after repetitive refining. Arsenic (As), cadmium (Cd) and lead (Pb) have been known as endocrine disrupting chemicals, which can bind with nuclear receptors to influence normal biological functions, and potentially induce inflammatory response to secret C-reactive protein (CRP) as a result of cardiovascular disease (CVD). In the decade, growth rate of CVD mortality of young adults has obviously increased. Therefore, this study aimed to investigate the correlation of urinary concentrations of heavy metals between physiological index and lifestyle, and whether heavy metals exposure affected gene expression of nuclear receptors genes to give rise to inflammatory response and trigger CRP secretion in dining-out young adults potentially for CVD development. One hundred dining-out young adults aged 18-45 were recruited in this study, and informed consent to provide their urine and blood samples and questionnaire information. Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the urinary concentrations of As, Cd and Pb. Quantitative real time polymerase chain reaction was used to detect the gene expressions of nuclear receptors genes, including hormone-related receptors (androgen receptor (AR), estrogen receptor α (ESR1), ESR2, G protein-coupled estrogen receptor 1 (GPER1)), lipometabolism-related receptors (peroxisome proliferator activated receptor α (PPARA), PPARG), and xenobiotic detoxification-related receptors (NR1I2 and AHR)). Plasma CRP was determined using enzyme-linked immunosorbent assay. This study found that there were correlations between As with Cd or Pb, and the young adults with higher frequency of cosmetics usage, seafood or fried food consumption had significant higher urinary arsenic levels. Study subjects who burned incense or consumed canned food more frequently were observed to have higher urinary Cd levels. Drinking water from water dispenser presented higher urinary Pb levels. Furthermore, urinary levels of heavy metals were divided by medians (As 29.72 μg/g cr, Cd 0.29 μg/g cr, Pb 2.60 μg/g cr), after logistic regression analysis, subjects with higher As exposure had the lower gene expressions of GPER1, PPARA and NR1I2. The higher Cd group had the higher gene expressions of AR, ESR2, GPER1 and PPARG. The higher Pb group had higher AHR and lower AR expressions. The CRP level was positively relevant to age and BMI. In addition, the results of partial least squares-structural equation modeling (PLS-SEM) indicated that young adults with higher levels of physiological indexes (age, arm, hip, BMI, and blood pressure) had higher CRP (path coefficient 0.485), and co-exposure of As, Cd and Pb presented higher gene expression of AHR and NR1I2 (path coefficient 0.335). Furthermore, the subjects with at least two potential CVD development syndromes inquired by TIA (transient ischemic attack) questionnaire and Rose questionaire had higher urinary Cd levels and decreased PPARA and NR1I2 expression. The findings of this study suggested that exposure to heavy metals relied on various types of dietary and living habit. Exposure to As, Cd and Pb might affect gene expression of hormone-related receptors (AR, ESR1, ESR2 and GPER1), lipometabolism-related receptors (PPARA and PPARG), and xenobiotic detoxification-related receptors (NR1I2 and AHR) to induce inflammatory response. Even though there was no correlation between exposure levels of heavy metals and CRP levels, subjects with CVD syndromes were observed to have higher urinary Cd levels and lower PPARA expression, indicating that Cd exposure might reduce PPARA expression to cause inflammation for CVD development. Therefore, it is necessary to reduce the chance of heavy metal exposure to avoid adverse health effect.

碩士
國立陽明大學
環境與職業衛生研究所
107
Background and Purpose Heavy metals and dioxins are released from incinerator, which lead various adverse health implications for resdients living nearby incineration. The purpose of this study is to evaluate the association of metal concentrations in urine and nail with two biomarkers of renal tubule disfunction and assess cancer risks of dioxin for adult and children living nearby a incinerator. Material and Methods Part1：Urine, nails and questionnaires were collected from students and their parents in the exposure and control groups based on the distance from their residence to the incinerator. Long-stay residents living in the incinerator for 20 years and over collected urine and questionnaires. Fourteen metals (arsenic, cadmium, chromium, copper, mercury, nickel, lead, selenium, zinc, gallium, indium, potassium, strontium and vanadium) in urine and nail concentrations were analyzed by ICP-MS: The concentrations of N-acetyl-β-D-glucosaminidase (NAG) and β2-microglobulin (B2M) in urine was used as biomarker of renal tubule dysfunction. Statistical methods were analyzed using SPSS versions 20 and R. Part2：Air concentrations of Dioxin were measured at three sites nearby an incinerator. Cancer risks of exposure to airborne dioxin were assessed for three age groups and gender. CMB-8.2 model was used to simulate the contribution of dioxins in Central Taiwan, which was used to identify contributing sources of dioxin at three sites. Results Part1：After adjusting for urinary creatinine, 14 urinary metal levels in the student exposure group were significantly higher than in the control group. However, the urinary Cd and Se levels in the adult exposure group were significantly lower than in the adult control group. Levels of As, Cd, Ni, Pb and Zn in nails for student exposure group were significantly higher than in the student control group. Levels of Cr, Ni and Pb in nails forthe adult exposure group were significantly higher than in the adult control group. Using multiple linear regression after adjusted for other potential confounders, the urinary concentration of fourteen metals for the student exposure group was significantly higher than in the student control group. However, urinary Cd and Se levels for adult exposure group were significantly lower than in the adult control group. The nail concentrations of Ni and Pb for the children exposure group was significantly higher than that of the children control group, but inverse relationship of V in the nail was found. Levels of Cr, Cu, Ni and Pb in nail for the adult exposure group had significantly higher than in the control group, but inverse relationship of As and V was shown.Two biomarkers of renal tubule dysfunction including urinary NAG and B2M levels in the children exposure group was significantly higher than in the control group. There were significant positive correlations between urinary As, Cd, Cr, Hg, Ni and Pb levels with NAG and B2M concentrations for children using multivariate regression analysis after adjusted for covariates. Urinary Hg levels in adults significantly positively correlated with NAG levels. Urinary levels of As, Cd, Cr, Hg, Ni and Pb significantly correlated with B2M concentration. Summary, urinary levels of six metals correlated with NAG and B2M levels, which indicated in children are more sensitive than in adults and NAG levels are more sensitive than B2M.Our results found Cr metal was the great sensitivity to kidney injury than in five metals. Part2：The cancer risks were 6.65E-07 to 1.19E-06 for children group, 5.97E-08 to 1.21E-07 for adults, 2.02E-08 and 4.10E-08 for older group, respectivley. Cancer risks for boy and girl children were greater than 10-6, which is an allowable limit for cancer risk. Contributions of dioxin of 30% using simulation by the CMB model was mainly responsible for the incinerator. Conclusions and Suggestions The results showed that the high uinray and nail metal levels for children living near the incineraton significantly correlated with the biomarkers of renal tubule dysfunction, appearing high levels of metal in urine and nail in residents obatinned from emitssion of the incinerator. In addiction, children living near at three sites the cancer risks were higher than those of the acceptable value (10-6). Therefore, it is vital for Taiwan Environmental Protection Agencies to strengthen the control of pollutants emitted by the incinerator to reduce the adverse health effects for surrounding residents.

碩士
國立陽明大學
腦科學研究所
101
Introduction: Affect has been recognized as an important factor of judgment and decision making. Numerous studies have demonstrated the effect of mere exposure, repeatedly presenting a stimulus to an individual, on increasing her/his positive attitude or preference for that stimulus. One speculation of this phenomenon is that repeated exposure modulates one’s affective state toward positive through enhanced familiarity. However, the neural mechanism underlying mere exposure effect (MEE) is still unclear. This study aimed at elucidating neural correlates of formation of mere exposure effect and their temporal profile. We hypothesized that repeated exposure increases positive affect through enhancing activation of the precuneus related to familiarity and reducing activation of visual cortex because of perceptual fluency. Methods: We conducted a subliminal experiment with a 2 (emotion; happy vs. neutral) x 2 (exposure; repeated vs. single) factorial design. Each emotion condition consisted of two exposure blocks (repeated and single) and one liking rating block. Each exposure block included one viewing stage and one implicit rating stage. During the viewing stage, subjects were presented 27 faces for 17 ms each and subsequently masked with a scrambled face image. Liking ratings for each exposed face and implicit ratings for unexposed neutral object images were measured by a four-button response pad. Thirty-three healthy volunteers were recruited in this study. Their magnetoencephalography (MEG) (Vectorview, Elekta Neuromag, Finland) were recorded and T1-weighted MRI (Siemens Medical, Erlangen, Germany) images were obtained. The MEG data were analyzed by estimating neural synchrony using phase-locking factor and spatiotemporal mapping using maximum contrast beamformer. For behavioral data, two separate two-way ANOVAs including the exposure (R/S) and facial expression (H/N) factors were performed. For neuroimaging data, paired t-test (NR vs. NS) and difference-in-difference estimate ((High group: NR-NS) vs. (Low group: NR-NS)) were performed. Results: The behavioral results showed that repeated exposure significantly increased positive affect. The left precuneus showed increased activity and the left paracentral gyrus showed decreased activity to repeated exposure. Furthermore, we divided subjects into high and low groups based on their implicit ratings. For both groups, the right cuneus showed decreased activity to repeated exposure. The left inferior parietal gyrus showed repetition suppression in the high group, but showed repetition enhancement in the low group. Besides, only the high group had repetition suppression in the midbrain. Conclusions: This study found that subliminal repeated exposure increased positive affect, which was associated with enhanced activation of the left precuneus and reduced activation of the left paracentral gyrus, the right cuneus, the left IPG and the midbrain. These findings suggest that possible mechanism underlying the subliminal mere exposure effect through elevated familiarity and eliminated arousal, perceptual loading, attention and alert.