A critical analysis of the prospects for the effective development of a regional approach to competition law in the ASEAN region

This thesis is an examination of the ASEAN’s prospects in establishing regional competition policy in the Southeast Asia region, a topic of contemporary relevance in light of the ASEAN’s recent foray into the economic integration field on 31 December 2015. It questions whether the current approach undertaken by the ASEAN could contribute to an effective regional competition policy under the regional market integration. In answering this question, the thesis first critically surveys the current terrain of regional competition laws and policies in order to determine the possible existence of an optimal template. It argues that although the EU model is oft used as a source of inspiration, each regional organisation conceives different configurations of the model in order to best adjust to the local regional contexts. The thesis makes an inquiry into the narratives of the ASEAN’s competition policy, as well as the ASEAN’s specific considerations in the development of competition policy, before comparing the findings to the actual approaches taken by the ASEAN in its pursuit of regional competition policy. This thesis reveals that the actual approach taken by the ASEAN demonstrates an important discrepancy from the economic integration goal. The ASEAN applies a soft harmonisation approach regarding substantive competition law while refraining from establishing a centralised institution or a representative institution. The sole organ with regards to competition policy at the regional level is an expert organ. The thesis also conducts an investigation into the reception of the ASEAN’s regional policy by the member states in order to ascertain the possibility of the achievement of the ASEAN’s aspiration of regional competition policy. The study reveals that despite some shared similarities in the broad principles of competition law amongst the member states, the various competition law regimes are not harmonised thus creating challenging obstacle to the ASEAN’s ambition. The thesis then concludes that the ASEAN’s approach to regional competition law is unlikely to be effective.

PERCEPTION AND OPINION OF CHILDREN, FAMILY PARENTS REGARDING THE SERVICES AND INFORMATION PRODUCTS OFFERED BY THE CHILDREN'S LIBRARY "ALVAREZ MIRIAM BRENES"

Presents the results of the study on the perceptions and views of children, fathers and mothers in relation to the services and products Children's Library "Miriam Alvarez Brenes" National University, developed by the Institute of Social Studies Population (IDESP), in collaboration with the Library staff Pretend that provided inputs to become key elements in making decisions and setting policies emanating from the authorities responsible for the proper development and expansion of activities and services that are to be implemented in selected communities will benefit of this project.

CONTRIBUTION OF THE LIBRARY CHILDREN "ALVAREZ MIRIAM BRENES" AND FAMILY IN THE FORMATION OF HABITS OF READING UNIVERSITY GARDENS CHILD POPULATION I AND II, Heredia, COSTA RICA: YEAR 2007 "

Constantly making efforts to strengthen reading habits in children from their earliest years of life, a process in which the family is established as the primary basis for the child to achieve the taste and interest in books. The school as being key to education supports and strengthens the skills taught in the home, with the help of technologies such as computers, disk reading, television, among other means, by which (as) children (as) found a door of communication with the outside world and everything around them. The children's library tends to use these technological means to attract children to reading, generating and taste for the various information resources, which over time will become a habit.This research is based on the "Contribution of the Library Miriam Alvarez Brenes and family in the formation of reading habits of children of the community of Garden I and II University in Heredia, through advocacy, in 2007 "

Epidemiology and genetic architecture of blood pressure: a family based study of Generation Scotland

Hypertension is a major risk factor for cardiovascular disease and mortality, and a growing global public health concern, with up to one-third of the world’s population affected. Despite the vast amount of evidence for the benefits of blood pressure (BP) lowering accumulated to date, elevated BP is still the leading risk factor for disease and disability worldwide. It is well established that hypertension and BP are common complex traits, where multiple genetic and environmental factors contribute to BP variation. Furthermore, family and twin studies confirmed the genetic component of BP, with a heritability estimate in the range of 30-50%. Contemporary genomic tools enabling the genotyping of millions of genetic variants across the human genome in an efficient, reliable, and cost-effective manner, has transformed hypertension genetics research. This is accompanied by the presence of international consortia that have offered unprecedentedly large sample sizes for genome-wide association studies (GWASs). While GWAS for hypertension and BP have identified more than 60 loci, variants in these loci are associated with modest effects on BP and in aggregate can explain less than 3% of the variance in BP. The aims of this thesis are to study the genetic and environmental factors that influence BP and hypertension traits in the Scottish population, by performing several genetic epidemiological analyses. In the first part of this thesis, it aims to study the burden of hypertension in the Scottish population, along with assessing the familial aggregation and heritialbity of BP and hypertension traits. In the second part, it aims to validate the association of common SNPs reported in the large GWAS and to estimate the variance explained by these variants. In this thesis, comprehensive genetic epidemiology analyses were performed on Generation Scotland: Scottish Family Health Study (GS:SFHS), one of the largest population-based family design studies. The availability of clinical, biological samples, self-reported information, and medical records for study participants has allowed several assessments to be performed to evaluate factors that influence BP variation in the Scottish population. Of the 20,753 subjects genotyped in the study, a total of 18,470 individuals (grouped into 7,025 extended families) passed the stringent quality control (QC) criteria and were available for all subsequent analysis. Based on the BP-lowering treatment exposure sources, subjects were further classified into two groups. First, subjects with both a self-reported medications (SRMs) history and electronic-prescription records (EPRs; n =12,347); second, all the subjects with at least one medication history source (n =18,470). In the first group, the analysis showed a good concordance between SRMs and EPRs (kappa =71%), indicating that SRMs can be used as a surrogate to assess the exposure to BP-lowering medication in GS:SFHS participants. Although both sources suffer from some limitations, SRMs can be considered the best available source to estimate the drug exposure history in those without EPRs. The prevalence of hypertension was 40.8% with higher prevalence in men (46.3%) compared to women (35.8%). The prevalence of awareness, treatment and controlled hypertension as defined by the study definition were 25.3%, 31.2%, and 54.3%, respectively. These findings are lower than similar reported studies in other populations, with the exception of controlled hypertension prevalence, which can be considered better than other populations. Odds of hypertension were higher in men, obese or overweight individuals, people with a parental history of hypertension, and those living in the most deprived area of Scotland. On the other hand, deprivation was associated with higher odds of treatment, awareness and controlled hypertension, suggesting that people living in the most deprived area may have been receiving better quality of care, or have higher comorbidity levels requiring greater engagement with doctors. These findings highlight the need for further work to improve hypertension management in Scotland. The family design of GS:SFHS has allowed family-based analysis to be performed to assess the familial aggregation and heritability of BP and hypertension traits. The familial correlation of BP traits ranged from 0.07 to 0.20, and from 0.18 to 0.34 for parent-offspring pairs and sibling pairs, respectively. A higher correlation of BP traits was observed among first-degree relatives than other types of relative pairs. A variance-component model that was adjusted for sex, body mass index (BMI), age, and age-squared was used to estimate heritability of BP traits, which ranged from 24% to 32% with pulse pressure (PP) having the lowest estimates. The genetic correlation between BP traits showed a high correlation between systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) (G: 81% to 94%), but lower correlations with PP (G: 22% to 78%). The sibling recurrence risk ratio (λS) for hypertension and treatment were calculated as 1.60 and 2.04 respectively. These findings confirm the genetic components of BP traits in GS:SFHS, and justify further work to investigate genetic determinants of BP. Genetic variants reported in the recent large GWAS of BP traits were selected for genotyping in GS:SFHS using a custom designed TaqMan® OpenArray®. The genotyping plate included 44 single nucleotide polymorphisms (SNPs) that have been previously reported to be associated with BP or hypertension at genome-wide significance level. A linear mixed model that is adjusted for age, age-squared, sex, and BMI was used to test for the association between the genetic variants and BP traits. Of the 43 variants that passed the QC, 11 variants showed statistically significant association with at least one BP trait. The phenotypic variance explained by these variant for the four BP traits were 1.4%, 1.5%, 1.6%, and 0.8% for SBP, DBP, MAP, and PP, respectively. The association of genetic risk score (GRS) that were constructed from selected variants has showed a positive association with BP level and hypertension prevalence, with an average effect of one mmHg increase with each 0.80 unit increases in the GRS across the different BP traits. The impact of BP-lowering medication on the genetic association study for BP traits has been established, with typical practice of adding a fixed value (i.e. 15/10 mmHg) to the measured BP values to adjust for BP treatment. Using the subset of participants with the two treatment exposure sources (i.e. SRMs and EPRs), the influence of using either source to justify the addition of fixed values in SNP association signal was analysed. BP phenotypes derived from EPRs were considered the true phenotypes, and those derived from SRMs were considered less accurate, with some phenotypic noise. Comparing SNPs association signals between the four BP traits in the two model derived from the different adjustments showed that MAP was the least impacted by the phenotypic noise. This was suggested by identifying the same overlapped significant SNPs for the two models in the case of MAP, while other BP traits had some discrepancy between the two sources

Normative conflicts in international investment law: the case of environmental law

This dissertation investigates the relationship between investment and environmental obligations from the perspective of international investment law. In order to do so, the dissertation will consider how these obligations might enter into conflicts and what tools are available to investment tribunals to solve these normative conflicts. The dissertation analyses in order interpretative techniques, conflict resolution tools available in general international law, as expressed in the Vienna Convention on the Law of Treaties, and finally express clauses in international investment agreements. The dissertation includes the review of some relevant case law arising from investment agreements in investment treaty tribunals, to discover how in practice these conflict resolution tools are applied and to assess their effectiveness. This dissertation places itself squarely within the debate between the unity and the fragmentation of international law; therefore it tackles the issue of normative conflicts resolution in a dispute settlement environment with the view of gauging their value in maintaining the unity of international law and defuse the risk of fragmentation. The dissertation can only conclude that much work remains to be done, including by providing a more comprehensive taxonomy of possible interventions, both on the legal and political sphere.

Protecting the Family Farm in Divorce

Nearly half of all U.S. marriages end in divorce, but how do divorces impact farmers? What can farmers do to protect their property and assets from the financial devastation of divorce? How can an extended family use estate planning to protect the family farm from divorce?

Gender and East Asian Welfare States: from Confucianism to Gender Equality

How can we understand the gender logic underpinning the welfare states/systems of East Asia? Does the comparative literature, which has largely been concerned with western Welfare states, whether in The Three Worlds of Welfare Capitalism (Esping-Andersen 1990), or in gender-based analysis of the male breadwinner model (Lewis 1992, 2001, 2006), have anything to offer in understanding the gender assumptions underpinning East Asian welfare states? Are the welfare systems of East Asian countries distinctive, with Confucian assumptions hidden beneath the surface commitment to gender equality? We will use the (mainly western) comparative literature, but argue that Confucian influences remain important, with strong assumptions of family, market and voluntary sector responsibility rather than state responsibility, strong expectations of women’s obligations, without compensating rights, a hierarchy of gender and age, and a highly distinctive, vertical family structure, in which women are subject to parents-in-law. In rapidly changing economies, these social characteristics are changing too. But they still put powerful pressures on women to conform to expectations about care, while weakening their rights to security and support. Nowhere do welfare states’ promises bring gender equality in practice. Even in Scandinavian countries women earn less, care more, and have less power than men. We shall compare East Asian countries (Japan, Korea, Taiwan where possible) with some Western ones, to argue that some major comparative data (e.g. OECD) show the extreme situation of women in these countries. Some fine new qualitative studies give us a close insight into the experience of mothers, including lone and married mothers, which help us to understand how far the gender assumptions of welfare states are from Scandinavia’s dual earner model. There are signs of change in society as well as in economy, and room for optimism that women’s involvement in social movements and academic enquiry may be challenging Confucian gender hierarchies.

Beyond the Spanish classics - The ephemeral awakening of the history of international law in pre-democratic Spain

Cuadernos para el Diálogo (1963-1978) played a key-role in nurturing the intellectual soil for the Spanish Transition to democracy and it has spawned an extensive amount of literature among historians. This work links for the first time the course of this emblematic monthly journal with the short-lived period of methodological and historiographical innovation of Revista Española de Derecho Internacional under the direction of the international jurist Mariano Aguilar Navarro.

Theod. I. F. Graswinckeli, I.C. Delphensis. Stricturae ad censuram Ioannis à Felden I.U.D. ad libros Hugonis Grotii De iure belli ac pacis.

Signatures: A-K¹² L¹⁰.

Receptor activity-modifying protein-directed G protein signaling specificity for the calcitonin gene-related peptide family of receptors

The calcitonin gene-related peptide (CGRP) family of G protein- coupled receptors (GPCRs) is formed through the association of the calcitonin receptor-like receptor (CLR) and one of three receptor activity-modifying proteins (RAMPs). Binding of one of the three peptide ligands, CGRP, adrenomedullin (AM), and intermedin/adrenomedullin 2 (AM2), is well known to result in aGαs-mediated increase in cAMP. Here we used modified yeast strains that couple receptor activation to cell growth, via chimeric yeast/Gα subunits, and HEK-293 cells to characterize the effect of different RAMP and ligand combinations on this pathway. We not only demonstrate functional couplings to both Gαs and Gαq but also identify a Gαi component to CLR signaling in both yeast and HEK-293 cells, which is absent in HEK-293S cells. We show that the CGRP family of receptors displays both ligand- and RAMPdependent signaling bias among the Gαs, Gαi, and Gαq/11 pathways. The results are discussed in the context of RAMP interactions probed through molecular modeling and molecular dynamics simulations of the RAMP-GPCR-G protein complexes. This study further highlights the importance of RAMPs to CLR pharmacology and to bias in general, as well as identifying the importance of choosing an appropriate model system for the study of GPCR pharmacology.

Failing to meet expectations:the meaning of intimate partner violence for Pakistanis

Background: Intimate Partner Violence (IPV) is a major social and public health problem affecting people across cultures, religions and societies. Much research has been undertaken to offer understanding and explanations of this phenomenon, its determinants, and its consequences in developed countries around the world. However, there is still a paucity of research on IPV in many areas of the developing world such as Pakistan. Although various studies have been conducted to demonstrate the prevalence of IPV in the country, none of the studies have tried to explore the meaning of IPV from the perspective of Pakistani people. Aim: This study aimed to explore understandings of Pakistani men and women of IPV. It aimed to develop a theory to explain the meaning of IPV and the process through which it occurs, from the perspective of Pakistani people. Methods: The study utilised a qualitative approach with constructivist grounded theory methods and analysis techniques. Data was collected from Karachi, Pakistan and Sheffield, UK. Forty one people (20 from Pakistan and 21 from UK) participated in the study. Findings: The participants identified IPV as a serious concern. Although verbal abuse is often included in definitions of IPV, the participants did not consider shouting, raising the voice or scolding as a type of violence. Hitting, beating, pushing, throwing objects, and pulling hair were identified as acts of physical violence, and non-consensual sex was identified as a form of sexual abuse. Participants identified failure to meet role expectations of a husband or wife as a key contributor to the development of conflict between partners which could lead to IPV. Examples of various expectations from a wife include completing household chores, looking after husband, looking after children, looking after in laws, respecting and adjusting to in-law's customs and traditions. Important expectation from a husband include provision of finances, acting as a bridge, maintaining a balance between his wife and other family members particularly his mother and sisters, and taking the responsibility for his wife and children. Failure to meet these expectations could contribute to conflict and subsequent violence. This appeared to be shaped by cultural issues such as common use of arranged marriages, the rarity of divorce and the centrality of the extended family to the intimate partnership. Implications: Any interventions aimed at reducing IPV in Pakistani people must consider the meaning and causes of IPV from the perspective of that group.

Family supportive work environment, perceptions of the employment relationship and employee work outcomes

Data obtained from employed parents and their supervisors (N=230) in twelve South Korean organizations were used to test a model of the antecedents and outcomes of organizational social exchange. Structural equation modeling (SEM) results showed family supportive supervisor and perceived organizational family support to be related to organizational social exchange. Additionally, organizational social exchange was shown to be related to contextual performance and work withdrawal but indirectly through organization-based self-esteem. We discuss the implications of these findings for managing the employee-organization relationship in an increasingly diverse workforce.

Teaching / learning process through the case method in the law degree

This project in teaching innovation and improvement aims to disseminate the case method as one of the most innovative educational instruments inteaching of Law in general, and specifically with regard to Family and Inheritance Law. The methodology used ensures learning through a legal conflict, which must be resolved by the students themselves from different viewpoints as legal agents. This is an activity in teaching innovation, in which students become the protagonists. Participation is voluntary, and the main aim is student motivation. The subject's aim is for students to learn public speaking skills fundamental to the profession while familiarising themselves with judicial practice. Theteacher sets up a legal conflict in order for students to resolve the dispute as legal agents with divergent viewpoints - in other words, as judges, attorneys, lawyers and so on. The project seeks alternatives to traditional teaching methods and is an innovative teaching method aimed at professionally training future lawyers as well as being a model that involves students more in their own learning.

The role of cancer related inflammation, Src family kinases and matrix metalloproteinase 9 in colorectal cancer

Colorectal cancer (CRC) is the third most common cancer in the UK with 41,000 new cases diagnosed in 2011. Despite undergoing potentially curative resection, a significant amount of patients develop recurrence. Biomarkers that aid prognostication or identify patients who are suitable for adjuvant treatments are needed. The TNM staging system does a reasonably good job at offering prognostic information to the treating clinician, but it could be better and identifying methods of improving its accuracy are needed. Tumour progression is based on a complex relationship between tumour behaviour and the hosts’ inflammatory responses. Sustained tumour cell proliferation, evading growth suppressors, resisting apoptosis, replicative immortality, sustained angiogenesis, invasion & metastasis, avoiding immune destruction, deregulated cellular energetics, tumour promoting inflammation and genomic instability & mutation have been identified as hallmarks. These hallmarks are malignant behaviors are what makes the cell cancerous and the more extreme the behaviour the more aggressive the cancer the more likely the risk of a poor outcome. There are two primary genomic instability pathways: Microsatellite Instability (MSI) and Chromosomal Instability (CI) also referred to as Microsatellite Stability (MSS). Tumours arising by these pathways have a predilection for specific anatomical, histological and molecular biological features. It is possible that aberrant molecular expression of genes/proteins that promote malignant behaviors may also act as prognostic and predictive biomarkers, which may offer superior prognostic information to classical prognostic features. Cancer related inflammation has been described as a 7th hallmark of cancer. Despite the systemic inflammatory response (SIR) being associated with more aggressive malignant disease, infiltration by immune cells, particularly CD8+ lymphocytes, at the advancing edge of the tumour have been associated with improved outcome and tumour MSI. It remains unknown if the SIR is associated with tumour MSI and this requires further study. The mechanisms by which colorectal cancer cells locally invade through the bowel remain uncertain, but connective tissue degradation by matrix metalloproteinases (MMPs) such as MMP-9 have been implicated. MMP-9 has been found in the cancer cells, stromal cells and patient circulation. Although tumoural MMP-9 has been associated with poor survival, reports are conflicting and contain relatively small sample sizes. Furthermore, the influence of high serum MMP-9 on survival remains unknown. Src family kinases (SFKs) have been implicated in many adverse cancer cell behaviors. SFKs comprise 9 family members BLK, C-SRC, FGR, FYN, HCK, LCK, LYN, YES, YRK. C-SRC has been the most investigated of all SFKs, but the role of other SFKs in cellular behaviors and their prognostic value remains largely unknown. The development of Src inhibitors, such as Dasatinib, has identified SFKs as a potential therapeutic target for patients at higher risk of poor survival. Unfortunately, clinical trials so far have not been promising but this may reflect inadequate patient selection and SFKs may act as useful prognostic and predictive biomarkers. In chapter 3, the association between cancer related inflammation, tumour MSI, clinicopathological factors and survival was tested in two independent cohorts. A training cohort consisting of n=182 patients and a validation cohort of n=677 patients. MSI tumours were associated with a raised CRP (p=0.003). Hypoalbuminaemia was independently associated with poor overall survival in TNM stage II cancer (HR 3.04 (95% CI 1.44 – 6.43);p=0.004), poor recurrence free survival in TNM stage III cancer (HR 1.86 (95% 1.03 – 3.36);p=0.040) and poor overall survival in CI colorectal cancer (HR 1.49 (95% CI 1.06 – 2.10);p=0.022). Interestingly, MSI tumours were associated with poor overall survival in TNM stage III cancer (HR 2.20 (95% CI 1.10 – 4.37);p=0.025). In chapter 4, the role of MMP-9 in colorectal cancer progression and survival was examined. MMP-9 in the tissue was assessed using IHC and serum expression quantified using ELISA. Serum MMP-9 was associated with cancer cell expression (Spearman’s Correlation Coefficient (SCC) 0.393, p<0.001)) and stromal expression (SCC 0.319, p=0.002). Serum MMP-9 was associated with poor recurrence-free (HR 3.37 (95% CI 1.20 – 9.48);p=0.021) and overall survival (HR 3.16 (95% CI 1.22 – 8.15);p=0.018), but tumour MMP-9 was not survival or MSI status. In chapter 5, the role of SFK expression and activation in colorectal cancer progression and survival was studied. On PCR analysis, although LYN, C-SRC and YES were the most highly expressed, FGR and HCK had higher expression profiles as tumours progressed. Using IHC, raised cytoplasmic FAK (tyr 861) was independently associated with poor recurrence free survival in all cancers (HR 1.48 (95% CI 1.02 – 2.16);p=0.040) and CI cancers (HR 1.50 (95% CI 1.02 – 2.21);p=0.040). However, raised cytoplasmic HCK (HR 2.04 (95% CI 1.11 – 3.76);p=0.022) was independently associated with poor recurrence-free survival in TNM stage II cancers. T84 and HT29 cell lines were used to examine the cellular effects of Dasatinib. Cell viability was assessed using WST-1 assay and apoptosis assessed using an ELISA cell death detection assay. Dasatinib increased T84 tumour cell apoptosis in a dose dependent manner and resulted in reduced expression of nuclear (p=0.008) and cytoplasmic (p=0.016) FAK (tyr 861) expression and increased nuclear FGR expression (p=0.004). The results of this thesis confirm that colorectal cancer is a complex disease that represents several subtypes of cancer based on molecular biological behaviors. This thesis concentrated on features of the disease related to inflammation in terms of genetic and molecular characterisation. MSI cancers are closely associated with systemic inflammation but despite this observation, they retain their relatively improved survival. MMP-9 is a feature of tissue remodeling during inflammation and is also associated with degradation of connective tissue, advanced T-stage and poor outcome when measured in the serum. The lack of stromal quantification due to TMA use rather than full sections makes the value of tumoural MMP-9 immunoreactivity in the prognostication and its association with MSI unknown and requires further study. Finally, SFK activation was also associated with SIR, however, only cytoplasmic HCK was independently associated with poor survival in patients with TNM stage II disease, the group of patients where identifying a novel biomarker is most needed. There is still some way to go before these biomarkers are translated into clinical practice and future work needs to focus on obtaining a reliable and robust scientific technique with validation in an adequately powered independent cohort.

Family as the Promoter of Independence Skills in Children with Motor Disabilities

This study developed an individualized proposal to promote, from the family context, the independence of two four-year-old children with motor disabilities. The proposal aimed at helping mothers and fathers to promote different skills within the family context. The results of this study revealed that when the families of children with disabilities are oriented, it is easier for them to start processes that otherwise would be postponed. As a result, it is recommended to create proposals to support the parents and help them to build their own family-growth processes and develop independence living skills in their children with motor disabilities.