Submitted by MATHEUS SENNA PEREIRA OGATA (mspogata@gmail.com) on 2018-09-18T00:16:15Z No. of bitstreams: 1 Dissertação (REFERENCIAS CORRGIIDAS) - Matheus Senna Pereira Ogata.pdf: 3338159 bytes, checksum: a4719346512d617a2a7beeb12f2c4a85 (MD5) / Approved for entry into archive by ROSANGELA APARECIDA LOBO null (rosangelalobo@btu.unesp.br) on 2018-09-18T17:16:07Z (GMT) No. of bitstreams: 1 ogata_msp_me_bot.pdf: 3338159 bytes, checksum: a4719346512d617a2a7beeb12f2c4a85 (MD5) / Made available in DSpace on 2018-09-18T17:16:07Z (GMT). No. of bitstreams: 1 ogata_msp_me_bot.pdf: 3338159 bytes, checksum: a4719346512d617a2a7beeb12f2c4a85 (MD5) Previous issue date: 2018-07-25 / Introdução: O tratamento padrão da retinopatia da prematuridade (ROP) é a ablação da retina avascular com laser ou crioterapia. No entanto, esta terapia pode deixar sequelas estruturais e visuais permanentes e não ser efetiva em casos de ROP posterior e agressiva. O fator de crescimento do endotélio vascular (VEGF) está envolvido na patogênese da ROP e a terapia antiangiogênica é opção nos casos de falha do tratamento padrão. Os potenciais efeitos adversos com o uso de antiangiogênicos em neonatos prematuros e a falta de evidências concretas sobre a eficácia destas drogas justifica uma revisão sistemática da literatura. Objetivo: Avaliar a eficácia e a segurança da terapia antiangiogênica, quando comparada com fotocoagulação a laser, crioterapia ou terapia combinada, no tratamento da ROP. Método: Uma revisão sistemática da literatura foi realizada, utilizando a metodologia da colaboração Cochrane e plataformas eletrônicas de busca para identificar estudos utilizando drogas antiangiogênicas no tratamento da ROP. A qualidade da evidência foi avaliada pelo sistema GRADE (Grading of Recommendations Assessment, Development and Evaluation). Resultados: Doze estudos foram incluídos nesta revisão (seis ensaios clínicos randomizados e seis estudos observacionais não randomizados), incluindo 677 recém-nascidos pré-termo (1288 olhos). Pelas metanálises, houve diferença estatística beneficiando a terapia anti-VEGF na ocorrência de progressão para descolamento de retina (RR 0.14 [IC 95% 0.05, 0.38] p=0.0001, I2 = 0%) e ocorrência de miopia ( Diferença de média ponderada 0.25 [IC 95% 0.14, 0.37] p<0.0001, I2 = 76%). No desfecho recorrência de ROP houve diferença estatística beneficiando o laser (RR 1.88 [IC 95% 1.34, 2.63] p=0.0003, I2 = 82%). Não houve porém, diferença entre a terapia anti-VEGF e o laser quanto à ocorrência de complicações oculares (RR 0.84 [IC 95% 0.34, 2.08] p=0.71, I2 = 0%). Na análise de sub grupo, na comparação entre as zonas de acometimento da ROP, o anti-VEGF apresentou menor risco de recorrência exigindo retratamento que o laser, em prematuros com ROP em zona I (RR 0.23 [IC 95% 0.11, 0.49] p=0.0001, I2 = 61%). A qualidade da evidência pelo GRADE variou de muito baixa a baixa. Conclusões: Há evidências de que a terapia anti-VEGF, usada como monoterapia, quando comparada ao laser, reduz o risco de progressão para descolamento de retina, a ocorrência de miopia e o risco de recorrência de ROP em prematuros com doença na zona I. No entanto, ainda faltam evidências de qualidade que permitam atestar a segurança da terapia, especialmente quanto aos potenciais efeitos sistêmicos em prematuros. Palavras-chave: Retinopatia da Prematuridade, antiangiogênicos, metanálise. / Background: The standard treatment of retinopathy of prematurity (ROP) is the ablation of the avascular retina with laser or cryotherapy. However, this therapy may leave permanent structural and visual sequelae and may not be effective in cases of posterior and aggressive ROP. Vascular endothelial growth factor (VEGF) is involved in the pathogenesis of ROP, and antiangiogenic therapy is an option in cases of failure of standard treatment. The potential adverse effects of the use of antiangiogenic drugs in preterm neonates and the lack of concrete evidence on the efficacy of these drugs justify a systematic review of the literature. Objective: To evaluate the efficacy and safety of antiangiogenic therapy, when compared with laser photocoagulation, cryotherapy or combination therapy, in the treatment of ROP. Method: A systematic review of the literature was conducted using the Cochrane collaboration methodology and electronic search platforms to identify studies using antiangiogenic drugs in the treatment of ROP. The quality of the evidence was evaluated by the GRADE system (Grading of Recommendations Assessment, Development, and Evaluation). Results: Twelve studies were included in this review (six randomized controlled trials - RCTs and six non-randomized observational studies), including 677 preterm infants. Through the meta-analyzes, there was a statistical difference benefiting anti-VEGF therapy in the occurrence of progression to retinal detachment (RR 0.14 [95% CI 0.05, 0.38] p = 0.0001, I2 = 0%) and myopia occurrence (Weighted mean difference 0.25 [95% CI 0.14, 0.37] p <0.0001, I2 = 76%). At the end of ROP recurrence, there was a statistical difference benefiting the laser (RR 1.88 [95% CI 1.34, 2.63], p = 0.0003, I2 = 82%). There was, however, no difference between the anti-VEGF therapy and the laser in the occurrence of ocular complications (RR 0.84 [95% CI 0.34, 2.08] p = 0.71, I2 = 0%). In the subgroup analysis, in the comparison between the ROP involvement zones, the anti-VEGF presented a lower risk of recurrence requiring retreatment than the laser in premature infants with zone I ROP (RR 0.23 [95% CI 0.11, 0.49] p = 0.0001, I2 = 61%).The quality of the GRADE evidence varied from very low to low. Conclusions: There is evidence that anti-VEGF therapy, used as monotherapy, when compared to laser, reduces the risk of progression to retinal detachment, the occurrence of myopia, and the risk of recurrence of ROP in preterm infants with the disease in zone I.However, there is still a lack of quality evidence to attest to the safety of therapy, especially regarding potential systemic effects in preterm infants.

Doctor of Philosophy / Department of Agronomy / Guihua Bai / Guorong Zhang / Fusarium head blight (FHB) is a devastating fungal disease in wheat, reducing not only grain yield but also quality. The pathogen produces the mycotoxin deoxynivalenol (DON) that induces severe toxicological problems in human and animals. Using host resistance has been the most efficient way to control the disease. To identify quantitative trait loci (QTLs) for FHB resistance in Chinese landrace Haiyanzhong (HYZ), a recombinant inbred lines (RILs) population derived from a cross between HYZ and Wheaton was developed. The RILs were evaluated for percentage of symptomatic spikelets (PSS) in three greenhouse experiments, and genotyped using simple sequence repeats (SSRs) and single nucleotide polymorphism (SNPs) developed from genotyping-by-sequencing (GBS). Eight QTLs were identified for type II (PSS) resistance on chromosomes 5A, 6B, 7D, 2B (2), 3B, 4B, and 4D, with 5A as the major QTL. Ten SNPs closely linked to 5A, 6B, and 2B QTLs were successfully converted to Kompetitave allelic specific PCR (KASP) assays. To identify common QTLs across different populations, we constructed high-density GBS-SNP maps in an additional four RIL populations derived from the Chinese landraces, Wangshuibai (WSB), Baishanyuehuang (BSYH), Huangfangzhu (HFZ), and Huangchandou (HCD) and conducted meta-analysis of the QTLs for FHB resistance using a consensus map developed from the five populations. We identified six MQTLs on chromosomes 3BS (2), 3A, 3D, 2D, and 4D and 23 tightly linked GBS-SNPs to the MQTLs. These GBS-SNPs were successfully converted to KASPs. The KASPs linked to MQTLs can be used for pyramiding these QTL in breeding programs. To quickly reduce FHB damage in U.S. hard winter wheat (HWW), we transferred Fhb1, a major QTL with stable effects on FHB resistance, from Ning7840 into three adapted HWW cultivars Overland, Jagger, and Overley, by marker-assisted backcross (MAB), and assessed the effect of Fhb1 on FHB resistance in these different backgrounds. The results showed that Fhb1 can significantly lower FHB severity, Fusarium-damaged kernel (FDK), and DON accumulation in the all the three HWW backgrounds. Some of the selected lines showed high levels of FHB resistance, but agronomically similar traits as recurrent parents, can be used as resistant parents to improve HWW FHB resistance.

Apesar de a qualidade ser considerada um dos principais determinantes da sobrevivência e prosperidade de prestadores de serviços via internet (eg, ZEITHAML; PARASURAMAM; MALHOTRA, 2000, 2002), existem muitas divergênciasna literatura a respeito da conceptualização, composição e consequências desse construto. A fim de ajudar no preenchimento dessa lacuna, este trabalho integrou os resultados quantitativos de 87 amostras independentes, reportados em 74 estudos (=35935), em um modelo metanalítico dos fatores da qualidade dos serviços prestados via internet (QSEI). Utilizando Rust e Oliver (1994) como referência teórica, os 10 fatores encontrados na literatura com frequência suficiente para análise (≥4) foram agrupados em 3 dimensões (qualidade do ambiente, do processo e do resultado) e associados à qualidade geral percebida, satisfação do cliente e intenção comportamental.Das 30 relações propostas, 25 alcançaram o ponto de corte estipulado (≥4) e puderam ser analisadas por meio da metanálise, quando se constatou que as relações eram significantes ao nível de 5%, bem como eram robustas no que diz respeito ao fail safe N. Com relação à magnitude dos efeitos observados, encontrou-se que o benefício funcional possui o maior efeito sobre a satisfação do cliente e a intenção comportamental, enquanto que a qualidade da informação possui o maior efeito sobre a qualidade geral percebida. O efeito do benefício funcional é maior do que o do benefício emocional tanto na satisfação do cliente quanto na intenção comportamental, sugerindo que as avaliações do cliente são mais cognitivas do que emocionais em contextos eletrônicos. O efeito do benefício funcional é maior do que o do benefício emocional tanto na satisfação do cliente quanto na intenção comportamental, sugerindo que as avaliações do cliente são mais cognitivas do que emocionais em contextos eletrônicos. Além disso, o benefício emocional, o benefício funcional e a confiabilidade estão entre os quatro fatores com maior efeito sobre a intenção comportamental, sugerindo que as intenções de comportamento do consumidor online são mais influenciadas pelos fatores associados ao final da experiência (dimensão qualidade do resultado). / Although quality has been recognizedas a major determinant of long-term performance and success for service providers on the internet (eg, ZEITHAML; PARASURAMAM; MALHOTRA, 2000, 2002), there are many divergences in the literature regarding the conceptualization, dimensionality and consequences of this construct. In order to help to fill this gap, it was integrated the quantitative results of 87 independent samples reported in 74 studies (N = 35935) in a meta-analytic model of service quality delivered through the Internet. Using Rust and Oliver (1994) as theoretical framework, the 10 factors found in the literature were grouped into 3 dimensions (environmental, process, and outcome quality) and associated to perceived quality, customer satisfaction, and behavioral intention. Thirty relationships were proposed, but only 25 of them reached the cutoff point (≥4)and were analyzed through the meta-analysis. These 25 relationships are significant at the 5% level and robust with regard to the fail safe N.The results indicate that the information quality is the most influential factor on the overall perceived quality, while the functional benefit is the most influential factor both on the customer satisfaction and behavioral intention. The functional benefit effect both on the customer satisfaction and behavioral intention is greater than that of emotional benefit, suggesting that the customer ratings are more cognitive than emotional in electronic contexts. Furthermore, the behavioral intention is most influenced by the outcome dimension factors (emotional benefit, functional benefit, and the reliability), demonstrating that the end of experience is very important for consumers at the internet.

This meta-analysis will investigate and compare existing research material on how Japanese and American high school students studying a foreign language are motivated by a belief that studying a foreign language will increase their future career opportunities. Reference material by appropriately versed authors will be used for this purpose. The concepts of attitude and motivation will be discussed together with the social context surrounding students from the two nations, such as the countries’ historical backgrounds and past and present educational circumstances. The reviewed literature revealed that there have been various reasons for reluctance in both countries to teaching foreign languages in school; however, more recent research points towards a transition and, particularly in the case of the United States, a new understanding is taking shape in regards to the need also for native English speakers to learn foreign languages.

Apesar de a qualidade ser considerada um dos principais determinantes da sobrevivência e prosperidade de prestadores de serviços via internet (eg, ZEITHAML; PARASURAMAM; MALHOTRA, 2000, 2002), existem muitas divergênciasna literatura a respeito da conceptualização, composição e consequências desse construto. A fim de ajudar no preenchimento dessa lacuna, este trabalho integrou os resultados quantitativos de 87 amostras independentes, reportados em 74 estudos (=35935), em um modelo metanalítico dos fatores da qualidade dos serviços prestados via internet (QSEI). Utilizando Rust e Oliver (1994) como referência teórica, os 10 fatores encontrados na literatura com frequência suficiente para análise (≥4) foram agrupados em 3 dimensões (qualidade do ambiente, do processo e do resultado) e associados à qualidade geral percebida, satisfação do cliente e intenção comportamental.Das 30 relações propostas, 25 alcançaram o ponto de corte estipulado (≥4) e puderam ser analisadas por meio da metanálise, quando se constatou que as relações eram significantes ao nível de 5%, bem como eram robustas no que diz respeito ao fail safe N. Com relação à magnitude dos efeitos observados, encontrou-se que o benefício funcional possui o maior efeito sobre a satisfação do cliente e a intenção comportamental, enquanto que a qualidade da informação possui o maior efeito sobre a qualidade geral percebida. O efeito do benefício funcional é maior do que o do benefício emocional tanto na satisfação do cliente quanto na intenção comportamental, sugerindo que as avaliações do cliente são mais cognitivas do que emocionais em contextos eletrônicos. O efeito do benefício funcional é maior do que o do benefício emocional tanto na satisfação do cliente quanto na intenção comportamental, sugerindo que as avaliações do cliente são mais cognitivas do que emocionais em contextos eletrônicos. Além disso, o benefício emocional, o benefício funcional e a confiabilidade estão entre os quatro fatores com maior efeito sobre a intenção comportamental, sugerindo que as intenções de comportamento do consumidor online são mais influenciadas pelos fatores associados ao final da experiência (dimensão qualidade do resultado). / Although quality has been recognizedas a major determinant of long-term performance and success for service providers on the internet (eg, ZEITHAML; PARASURAMAM; MALHOTRA, 2000, 2002), there are many divergences in the literature regarding the conceptualization, dimensionality and consequences of this construct. In order to help to fill this gap, it was integrated the quantitative results of 87 independent samples reported in 74 studies (N = 35935) in a meta-analytic model of service quality delivered through the Internet. Using Rust and Oliver (1994) as theoretical framework, the 10 factors found in the literature were grouped into 3 dimensions (environmental, process, and outcome quality) and associated to perceived quality, customer satisfaction, and behavioral intention. Thirty relationships were proposed, but only 25 of them reached the cutoff point (≥4)and were analyzed through the meta-analysis. These 25 relationships are significant at the 5% level and robust with regard to the fail safe N.The results indicate that the information quality is the most influential factor on the overall perceived quality, while the functional benefit is the most influential factor both on the customer satisfaction and behavioral intention. The functional benefit effect both on the customer satisfaction and behavioral intention is greater than that of emotional benefit, suggesting that the customer ratings are more cognitive than emotional in electronic contexts. Furthermore, the behavioral intention is most influenced by the outcome dimension factors (emotional benefit, functional benefit, and the reliability), demonstrating that the end of experience is very important for consumers at the internet.

OBJETIVO Avaliar as evidências quanto à associação entre síndrome metabólica e periodontite através de uma revisão sistemática da literatura e metanálise de estudos observacionais. MATERIAIS E MÉTODOS Os estudos foram acessados através de busca nas bases eletrônicas Medline, EMBASE e Biblioteca Cochrane e de busca manual para identificar estudos, observacionais, originais, realizados com população adulta, que avaliaram a associação entre síndrome metabólica e doença periodontal. Os estudos deveriam mencionar critério de diagnóstico para síndrome metabólica e pelo menos uma medida clínica para o diagnóstico de periodontite e apresentar as medidas de efeito através de razão de chance (OR), risco relativo (RR) ou taxa de prevalência (PR). Os dados foram extraídos por dois investigadores, de maneira independente. A metanálise dos estudos incluídos foi realizada utilizando-se modelos randômicos. RESULTADOS A revisão sistemática incluiu 17 estudos observacionais, que preencheram os critérios de inclusão. Na metanálise foram incluídos 11 estudos, totalizando dados de 38.189 pacientes. Encontrou-se associação entre síndrome metabólica e periodontite com um OR de 1,78 (IC 95% 1,38- 2,30), e heterogeneidade de i2=93%. Para investigar a alta heterogeneidade foram (1) rodadas análises sequenciais, excluindo-se um estudo por vez, (2) metarregressão avaliando-se isoladamente idade, tabagismo, critério de diagnóstico para síndrome metabólica e exame periodontal completo versus parcial, (3) análise de subgrupos analisando-se em separado estudos em população asiática e não asiática e análise de sensibilidade. A heterogeneidade foi reduzida de forma significativa quando subdividiu-se os estudos com origem em população asiática (OR 2,06, IC 95% 1,60– 2,85, i2= 83,1%) e em população não asiática (OR 1,12 IC 95% 1,04- 1,68, i2=65,3%). CONCLUSÃO Os achados deste estudo reportam uma associação significativa entre síndrome metabólica e doença periodontal. A falta de um número suficiente de estudos longitudinais impede que se estabeleça a direção desta associação. Devido a alta heterogeneidade encontrada, estudos de intervenção bem controlados são necessários para que se conheça a magnitude dessa associação. / PURPOSE To investigate the association of metabolic syndrome and periodontitis by means of a systematic review and a meta-analysis of observational studies. RESEARCH DESIGN AND METHODS The electronic databases Medline, EMBASE and The Cochrane Library were searched for observational studies that evaluated the association of Metabolic Syndrome and Periodontitis. Hand search was also done. Data extraction was performed by two reviewers independently. Pooled effect estimates were obtained by using random-effects meta-analysis. RESULTS Systematic review included 17 studies that fulfilled the inclusion criteria. Meta-analysis was done with 11 studies, providing data of 38.189 patients. The results showed that there is an association estimated in an OR of 1,78 (95%IC 1,38- 2,30) between metabolic syndrome and periodontitis. A high heterogeneity was present (i2=93%). To investigate heterogeneity (1) the meta-analysis was re-ran excluding studies one at a time, (2) univariate metaregression was performed analyzing smoke status, metabolic syndrome criteria and parcial versus complete periodontal record, (3) subgroup analysis splitting studies in those performed with Asiatic populations and with non-Asiatic populations and sensitivity analysis. The heterogeneity was reduced significantly when subgroup analysis was done, for Asiatic population an OR of 2,06 (95% IC 1,60-2,85) and i2= 83,1% and for non-Asiatic population an OR of 1,12 (95% IC 1,04- 1,68) and i2=65,3% were found. CONCLUSION This study showed a significant association between metabolic syndrome and periodontitis. The lack of longitudinal studies in this area prevent from setting the direction of this association. Due to the high heterogeneity found, interventional and well controlled studies are encouraged to elucidate the magnitude of this association.

Objectives: The thesis comprises two parts. Firstly, a systematic review (SR) systematically examined meta-analytic studies assessing the prevalence of sexual abuse in childhood. A meta-analysis sought to systematically identify and synthesise data from studies providing prevalence estimates of contact and non-contact child sexual abuse (CSA) as self-reported by adolescents within the past 10 years. Methods: Consistent with Cochrane Collaboration guidelines, the systemic review adopted a comprehensive search of electronic databases and additional sources, including communication with authors working in the field, and the use of ancestry and descendency approaches between February 2013 and March 2014. The meta-analysis also adopted an equally systematic search conducted from March 2013 to June 2014. Assessment of quality and risk of bias were conducted on the included studies using PRISMA criteria and STROBE guidelines. Results: The systematic review identified six meta-analytic studies for review. The quality of studies and the range of definitional and methodological factors studied varied; results sections were well covered, whereas, quality and risk of bias within studies were generally poorly addressed. Prevalence estimates varied considerably and high heterogeneity was consistent across all analyses. Nine population studies measuring prevalence of contact and non-contact CSA were included in the meta-analysis. Meta-analyses were conducted overall and across male and female populations. Prevalence estimates varied considerably across studies, with contact CSA ranging from 2% to 39.8% and overall non-contact CSA, estimates ranged from 1% to 24.6%. Substantial heterogeneity was present across all analyses and therefore findings should be interpreted with caution. Nevertheless, the findings were thought-provoking and most likely due to differences in definitions of CSA and inconsistent use of validated instruments. Conclusions: Child sexual abuse is an international problem which is highly pervasive across all societies and populations studied. Females consistently report higher rates of CSA than males, and some Asian countries, namely China, produce relatively lower CSA estimates, even controlling for a wide range of methodological factors and study characteristics. The considerable heterogeneity was apparent both between and within studies and it appears likely based on the current findings, and in the context of previous research, that there are a wide range of methodological and socio-demographic factors which moderate CSA prevalence estimates. More specifically, the lack of a universally recognised definition of CSA proves especially problematic for researchers. The issue is further complicated by use of non-standardised instruments and inconsistent reporting and dissemination of findings. There is a need for future epidemiological studies to adhere to universal guidelines using standard definitions, standardisation of instruments and standardisation of reporting and dissemination to facilitate development of health policies, resource allocation and prevention initiatives for clinical and social services.

Objectives: This thesis includes two distinct pieces of work. A systematic literature review (SLR) aimed to identify, organise and evaluate constructs and measures of adjustment and adaptation to retirement (AAR), as these are currently used in the literature. A meta-analysis (MA) sought to systematically evaluate the evidence of the relationship between retirement and self-reported symptoms of depression in later life. Methods: For the SLR, a comprehensive list of electronic databases, and additional sources, were searched (March-May 2013). The identified constructs of AAR were evaluated in relation to their content, clarity and frequency of use. The identified measures were evaluated in relation to pre-defined psychometric properties and frequency of use. For the MA, an equally comprehensive search strategy was used (December 2012-March 2013). A metaanalysis and systematic assessment of risk of bias were carried out on the studies eventually included. Results: In the SLR, 27 measures of AAR were put forward for evaluation, and 6 distinct clusters of constructs of AAR were identified. AAR is defined inconsistently in this literature. Most measures that are used to assess these constructs are adapted or imported from other contexts (e.g. mental health, well-being, life-satisfaction). The 7 measures that related specifically to AAR (‘retirement satisfaction and role adjustment’) lacked detailed psychometric information. Eight non-randomised studies were included in the MA, 5 cohort studies and 3 cross-sectional studies. Studies were grouped and analysed according to these two design-type subgroups There was evidence of high dispersion of effect sizes, variable risk of bias and methodological and statistical heterogeneity between studies in both sub-groups – cohort (Q=640.728, df =4, p<0.001), cross-sectional (Q=76.611, df=2, p<0.001). Summary effects were therefore not meaningful. Sensitivity and sub-group analyses did not account for high heterogeneity of effect sizes. Conclusions: The SLR concluded that the variability in outcomes of research on AAR found in this literature may be underpinned, in part, by the different constructs and measures that are used. The 27 measures evaluated did not seem, at face-value, to measure the same construct; their psychometric properties also varied. The interpretation of outcomes, and comparisons between studies, in this area is hindered by this inconsistency. The MA concluded that the relationship between retirement and self-reported depressive symptoms seems to be complex and variable. Effect-sizes of individual studies were small, non-significant and highly dispersed, and heterogeneity of true effects was high. These results may be limited by confounding factors in primary studies. This is discussed and contextualised in relation to the use of non-randomised studies in meta-analysis.

As one of the most recommended strategies in decision making of contemporary medicine, evidence-based medicine (EBM) is attracting more and more attention. For EBM, the scientific evidences are obtained mainly from the randomized controlled trials (RCTs), systematic review and meta-analysis. In particular, meta-analysis can help researchers statistically combine several independent studies for a same clinical problem. In meta-analysis, Cohen's d and Hedges' g are among the most commonly used effect size measurements for continuous data. To compute these mean difference criteria, the sample mean and standard deviation are two conventional statistics reported in the literature. However, some other clinical studies may instead report the median, minimum and maximum values, and/or sample quartiles. Such a situation requires researchers to estimate the sample mean and standard deviation from these reported summary statistics. We note, however, that most existing estimators in the literature have some serious limitations. For this, we propose to improve the existing methods and extend them to three frequently encountered scenarios. In this thesis, we developed the optimal sample mean estimators, the normality test statistics and the updated Cohen's d mean difference criterion for three commonly encountered scenarios in meta-analysis. In Chapter 1, we gave a brief introduction on evidence-based medicine, meta-analysis and the summary data. In Chapter 2, we introduced our optimal estimators of the sample mean under the three scenarios, respectively. In Chapter 3, we proposed several methods for testing the normality of the underlying data. And in Chapter 4, we proposed to improve the famous Cohen's d and its relevant parameters. To assess the practical performance of our newly proposed methods, we also chose a few real data at the end of each chapter as illustrating examples. Numerical results of those studies indicated that our proposed methods have satisfactory performance both in theory and in practice. Following our new methodology, we also recommended an improved procedure for medical researchers to conduct meta-analysis. For illustration, we chose a meta-analysis in Chapter 5 on the effect of phytosterols to plasma CRP level (Rocha et al., 2016) to compare the results obtained from our recommended procedure and from the original methods. The results showed that our recommended procedure may lead to distinctly different results for a same clinical problem. To conclude the thesis, we expect that our newly proposed methods can be regarded as "rules of thumb" and will soon be widely applied in meta-analysis and evidence-based medicine.

Unlike achieved fertility, fertility intentions are often positively correlated with education. However, the conditions under which such a positive relationship exists are not yet well known. Using 86 pieces of research covering 13 European countries that were published between 1990 and 2011, we assess in a quantitative manner the temporal and cross-country variation in the relationship between educational attainment and reproductive intentions. Because of the sequential nature of reproductive decisions and the gendered nature of each individual's life course, we look separately at childless women and women with one child, and compare women with men. Our findings show that both first and second birth intentions and educational attainment are positively correlated, but that this relationship - which is stronger for men than for women - tends to disappear when the normative value of a two-child family is reached. Structural labour market characteristics explain a good portion of the cross-country variance: the educational slope of first and second birth intentions is steeper in countries with large shares of women in vulnerable employment situations or in part-time employment, and is flatter in countries with gender-equal labour force participation and large shares of women in highly qualified employment.