El sudeste asiático : estructura y cambio de sus relaciones internacionales

 The essay addresses the international relations of the Southeast Asian región, with the purpose of identifying the main characteristics of its interaction with East Asia and the regional powers. The first part explores the origins of the term «Southeast Asia» and the regional order pre- World War II. The second and third sections focus on Cold War and post-Cold War developments, stressing the role of the Association of Southeast Asian Nations (ASEAN) as a vehicle for Southeast Asian relations with the Asia Pacific región. The fourth section examines Southeast Asian relations with the main powers: United States, China and Japan.El ensayo presenta una visión general de las relaciones internacionales del sudeste asiático, con el fin de identificar las principales características de su vinculación con el este de Asia y las principales potencias de la región. La primera parte del texto explora los orígenes del término «sudeste asiático» y del orden regional anterior a la Segunda Guerra Mundial. La segunda y tercera partes se centran en los desarrollos de la guerra y de la post Guerra Fría, haciendo hincapié en el rol de la Asociación de Naciones del Sudeste Asiático (ASEAN) como medio a través del cual sus miembros se insertan en la región del Asia Pacífico. La cuarta sección explora las relaciones del sudeste asiático con las principales potencias: Estados Unidos, China y Japón

The clinical utility of molecular diagnostic testing for primary immune deficiency disorders: a case based review

Primary immune deficiency disorders (PIDs) are a group of diseases associated with a genetic predisposition to recurrent infections, malignancy, autoimmunity and allergy. The molecular basis of many of these disorders has been identified in the last two decades. Most are inherited as single gene defects. Identifying the underlying genetic defect plays a critical role in patient management including diagnosis, family studies, prognostic information, prenatal diagnosis and is useful in defining new diseases. In this review we outline the clinical utility of molecular testing for these disorders using clinical cases referred to Auckland Hospital. It is written from the perspective of a laboratory offering a wide range of tests for a small developed country

Chemotherapy with BCNU in recurrent glioma: Analysis of clinical outcome and side effects in chemotherapy-naïve patients

Background: To date, standardized strategies for the treatment of recurrent glioma are lacking. Chemotherapy with the alkylating agent BCNU (1,3-bis (2-chloroethyl)-1-nitroso-urea) is a therapeutic option even though its efficacy and safety, particularly the risk of pulmonary fibrosis, remains controversial. To address these issues, we performed a retrospective analysis on clinical outcome and side effects of BCNU-based chemotherapy in recurrent glioma. Methods: Survival data of 34 mostly chemotherapy-naïve glioblastoma patients treated with BCNU at 1st relapse were compared to 29 untreated control patients, employing a multiple Cox regression model which considered known prognostic factors including MGMT promoter hypermethylation. Additionally, medical records of 163 patients treated with BCNU for recurrent glioma WHO grade II to IV were retrospectively evaluated for BCNU-related side effects classified according to the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 2.0. Results: In recurrent glioblastoma, multiple regression survival analysis revealed a significant benefit of BCNU-based chemotherapy on survival after relapse (p = 0.02; HR = 0.48; 95 % CI = 0.26–0.89) independent of known clinical and molecular prognostic factors. Exploratory analyses suggested that survival benefit was most pronounced in MGMT-hypermethylated, BCNU-treated patients. Moreover, BCNU was well tolerated by 46 % of the 163 patients analyzed for side effects; otherwise, predominantly mild side effects occurred (CTCAE I/II; 45 %). Severe side effects CTCAE III/IV were observed in 9 % of patients including severe hematotoxicity, thromboembolism, intracranial hemorrhage and injection site reaction requiring surgical intervention. One patient presented with a clinically apparent pulmonary fibrosis CTCAE IV requiring temporary mechanical ventilation. Conclusion: In this study, BCNU was rarely associated with severe side effects, particularly pulmonary toxicity, and, in case of recurrent glioblastoma, even conferred a favorable outcome. Therefore BCNU appears to be an appropriate alternative to other nitrosoureas although the efficacy against newer drugs needs further evaluation

Congenital Hydrocephalus and Abnormal Subcommissural Organ Development in Sox3 Transgenic Mice

Congenital hydrocephalus (CH) is a life-threatening medical condition in which excessive accumulation of CSF leads to ventricular expansion and increased intracranial pressure. Stenosis (blockage) of the Sylvian aqueduct (Aq; the narrow passageway that connects the third and fourth ventricles) is a common form of CH in humans, although the genetic basis of this condition is unknown. Mouse models of CH indicate that Aq stenosis is associated with abnormal development of the subcommmissural organ (SCO) a small secretory organ located at the dorsal midline of the caudal diencephalon. Glycoproteins secreted by the SCO generate Reissner's fibre (RF), a thread-like structure that descends into the Aq and is thought to maintain its patency. However, despite the importance of SCO function in CSF homeostasis, the genetic program that controls SCO development is poorly understood. Here, we show that the X-linked transcription factor SOX3 is expressed in the murine SCO throughout its development and in the mature organ. Importantly, overexpression of Sox3 in the dorsal diencephalic midline of transgenic mice induces CH via a dose-dependent mechanism. Histological, gene expression and cellular proliferation studies indicate that Sox3 overexpression disrupts the development of the SCO primordium through inhibition of diencephalic roof plate identity without inducing programmed cell death. This study provides further evidence that SCO function is essential for the prevention of hydrocephalus and indicates that overexpression of Sox3 in the dorsal midline alters progenitor cell differentiation in a dose-dependent manner

The Generation R Study: design and cohort update 2010

The Generation R Study is a population-based prospective cohort study from fetal life until young adulthood. The study is designed to identify early environmental and genetic causes of normal and abnormal growth, development and health during fetal life, childhood and adulthood. The study focuses on four primary areas of research: (1) growth and physical development; (2) behavioural and cognitive development; (3) diseases in childhood; and (4) health and healthcare for pregnant women and children. In total, 9,778 mothers with a delivery date from April 2002 until January 2006 were enrolled in the study. General follow-up rates until the age of 4 years exceed 75%. Data collection in mothers, fathers and preschool children included questionnaires, detailed physical and ultrasound examinations, behavioural observations, and biological samples. A genome wide association screen is available in the participating children. Regular detailed hands on assessment are performed from the age of 5 years onwards. Eventually, results forthcoming from the Generation R Study have to contribute to the development of strategies for optimizing health and healthcare for pregnant women and children

El sudeste asiático : estructura y cambio de sus relaciones internacionales

 The essay addresses the international relations of the Southeast Asian región, with the purpose of identifying the main characteristics of its interaction with East Asia and the regional powers. The first part explores the origins of the term «Southeast Asia» and the regional order pre- World War II. The second and third sections focus on Cold War and post-Cold War developments, stressing the role of the Association of Southeast Asian Nations (ASEAN) as a vehicle for Southeast Asian relations with the Asia Pacific región. The fourth section examines Southeast Asian relations with the main powers: United States, China and Japan.El ensayo presenta una visión general de las relaciones internacionales del sudeste asiático, con el fin de identificar las principales características de su vinculación con el este de Asia y las principales potencias de la región. La primera parte del texto explora los orígenes del término «sudeste asiático» y del orden regional anterior a la Segunda Guerra Mundial. La segunda y tercera partes se centran en los desarrollos de la guerra y de la post Guerra Fría, haciendo hincapié en el rol de la Asociación de Naciones del Sudeste Asiático (ASEAN) como medio a través del cual sus miembros se insertan en la región del Asia Pacífico. La cuarta sección explora las relaciones del sudeste asiático con las principales potencias: Estados Unidos, China y Japón