FOSTER TO ADOPT: PIPELINE TO FAILURE AND THE NEED FOR CONCURRENT PLANNING REFORM

FOSTER TO ADOPT: PIPELINE TO FAILURE AND THE NEED FOR CONCURRENT PLANNING REFOR

Perception of English as a second language

Thesis (B.Sc)--University of Hong Kong, 2008.Also available in print.Also available online.Includes bibliographical references (leaves 30-31).A dissertation submitted in partial fulfilment of the requirements for the Bachelor of Science (Speech and Hearing Sciences), The University of Hong Kong, June 30, 2008.published_or_final_versionSpeech and Hearing SciencesBachelorBachelor of Science in Speech and Hearing Science

Brain matter matters : renewal in the human brain

Many cells have a shorter life span than the organism itself and are continuously being replaced. However, for many cell types in the human body it is still largely unknown whether they turn over at all once development is complete. The work presented in this thesis focuses on understanding the occurrence of cell renewal in the human brain and how it may affect brain function. We further explore if the ability of cell renewal may also be affected in the diseased brain. To investigate cell turnover in the human brain we used a methodology developed in the Frisén laboratory. The developed strategy takes the advantage of the integration of the 14C (carbon-14) isotope, produced from the nuclear bomb tests during the Cold War, into genomic DNA, to determine the age of cells in humans. In Paper I we assessed the dynamics of oligodendrocyte generation and myelination in the human brain. We found that the number of oligodendrocytes in the corpus callosum is established in childhood and remains constant thereafter. We revealed that myelin is continually exchanged, whereas white matter oligodendrocytes are remarkably stable with an annual exchange of 1 in 300 oligodendrocytes. This suggests that myelin modulation in humans may be carried out by mature oligodendrocytes. Moreover, we also found different kinetics of oligodendrocyte generation and turnover between gray and white matter, with a longer period of oligodendrocyte generation and higher turnover rate throughout life in gray matter, showing the possibility of de novo myelination in the sparsely myelinated cortex. However, how generation kinetics of the oligodendrocyte population may change under pathological conditions such as in the demyelination disease multiple sclerosis has been unknown. In Paper II we investigated the oligodendrocyte generation dynamics in multiple sclerosis patients. We observed no induced generation of oligodendrocytes in normal appearing white matter, except in a subsets of multiple sclerosis patients with a very aggressive progression of the disease. We also revealed that oligodendrocytes in remyelination lesions were old in multiple sclerosis patients, showing that existing and not new oligodendrocytes are regenerating myelin in multiple sclerosis. In Paper III we examined the extent of postnatal olfactory bulb neurogenesis in humans. We report that the olfactory bulb neurons are almost as old as the individuals, establishing that there is very limited, if any, postnatal neurogenesis in the human olfactory bulb. Together the findings presented in this thesis highlight a conceptual and fundamental difference in human brain plasticity compared to other mammals

New insights into the role of soluble E-cadherin in tumor angiogenesis

A key to successful metastasis is the formation of new vasculature, known as angiogenesis. Therefore, it is of great interest to unravel the underlying molecular mechanisms of tumor angiogenesis. Cadherins are a major class of cell surface receptors. The loss of cadherins, especially E-cadherin, is a well-established marker for tumor metastasis. Loss of E-cadherin is also a defining characteristic of several carcinomas, such as lobular carcinoma of the breast, and de-differentiated endometrioid carcinoma of the endometrium and ovary, which are known to be associated with more aggressive tumor behavior. Although E-cadherin is synthesized as a transmembrane molecule, its extracellular domain can be enzymatically cleaved off and released as a soluble E-cadherin (sE-cad), and this accounts for the loss of E-cadherin function or expression that has been implicated in tumor progression and metastasis. Importantly, sE-cad is present at high levels in the serum and malignant ascites of ovarian carcinoma patients. Nevertheless, little is known about how this essential protein dictates metastasis. Hitherto, many studies have given attention only to the dominant negative role of the loss of E-cadherin in weakening cell-cell adhesion, however, it is not known if sE-cad has biological activity in itself. In addition, the release mechanism of sE-cad has remained elusive. Here we show for the first time that sE-cad is a pivotal regulator of angiogenesis. We further show that exosomes are a novel major platform for the cleavage and release of sE-cad in vitro, in vivo and in patients’ derived samples (Nat Commun, 9: 2270)

Preparation of highly and generally enriched mammalian tissues for solid state NMR.

An appreciable level of isotope labelling is essential for future NMR structure elucidation of mammalian biomaterials, which are either poorly expressed, or unexpressable, using micro-organisms. We present a detailed protocol for high level (13)C enrichment even in slow turnover murine biomaterials (fur keratin), using a customized diet supplemented with commercial labelled algal hydrolysate and formulated as a gel to minimize wastage, which female mice consumed during pregnancy and lactation. This procedure produced approximately eightfold higher fur keratin labelling in pups, exposed in utero and throughout life to label, than in adults exposed for the same period, showing both the effectiveness, and necessity, of this approach.The authors would like to acknowledge funding from the Biotechnology and Biological Sciences Research Council for DGR and RR; Engineering and Physical Sciences Research Council for WYC and VWCW; National Institute of Health Research for RAB.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10858-015-9977-

Treating glioblastoma multiforme with selective high-dose liposomal doxorubicin chemotherapy induced by repeated focused ultrasound

Feng-Yi Yang1, Ming-Che Teng1, Maggie Lu2, Hsiang-Fa Liang2, Yan-Ru Lee1, Chueh-Chuan Yen3, Muh-Lii Liang4,5, Tai-Tong Wong51Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 2Drug Delivery Laboratory, Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, 3Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taipei, 4Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, 5Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taipei, TaiwanBackground: High-dose tissue-specific delivery of therapeutic agents would be a valuable clinical strategy. We have previously shown that repeated transcranial focused ultrasound is able to increase the delivery of Evans blue significantly into brain tissue. The present study shows that repeated pulsed high-intensity focused ultrasound (HIFU) can be used to deliver high-dose atherosclerotic plaque-specific peptide-1 (AP-1)-conjugated liposomes selectively to brain tumors.Methods: Firefly luciferase (Fluc)-labeled human GBM8401 glioma cells were implanted into NOD-scid mice. AP-1-conjugated liposomal doxorubicin or liposomal doxorubicin alone was administered followed by pulsed HIFU and the doxorubicin concentration in the treated brains quantified by fluorometer. Growth of the labeled glioma cells was monitored through noninvasive bioluminescence imaging and finally the brain tissue was histologically examined after sacrifice.Results: Compared with the control group, the animals treated with 5 mg/kg injections of AP-1 liposomal doxorubicin or untargeted liposomal doxorubicin followed by repeated pulsed HIFU not only showed significantly enhanced accumulation of drug at the sonicated tumor site but also a significantly elevated tumor-to-normal brain drug ratio (P < 0.001). Combining repeated pulsed HIFU with AP-1 liposomal doxorubicin or untargeted liposomal doxorubicin has similar antitumor effects.Conclusion: This study demonstrates that targeted or untargeted liposomal doxorubicin, followed by repeated pulsed HIFU, is a promising high-dose chemotherapy method that allows the desired brain tumor region to be targeted specifically.Keywords: repeated focused ultrasound, interleukin-4 receptor, blood-brain barrier, brain tumor, target drug deliver

Improved stability of blood glucose measurement in humans using near infrared spectroscopy

Abstract. Near infrared (NIR) spectroscopy has become a promising technique for blood glucose monitoring. However, an appropriate model of spectral response in humans is yet to be determined because of the reliability problem. In this study, 48 subjects were recruited. The subjects' left forearms were scanned using near infrared spectroscopy to obtain NIR spectra. Simultaneously, a blood sample of glucose was drawn. A new method based on Monte Carlo approach is applied for partial least squares (PLS), named as PLS MC , is proposed. A large numbers of models are built from calibration subsets which are randomly selected from the whole calibration set in order to minimize the noises. It is then determining the mean value over the models with high correlation and small prediction errors. The results show that the method can enhance the stability of PLS model. Also, the performance of the PLS MC shows more accurate prediction results as compared with conventional PLS

Poliserosite, artrite e doença respiratória em leitões: estudo de caso

O complexo da poliserosite em suínos é causado por múltiplos factores, em particular pelo agente Haemophilus parasuis (HPS), que tem vindo a causar vários problemas em suínos, quer ao nível respiratório, quer nas articulações. O agente HPS é o responsável pela Doença de Glässer (DG), caracterizada por uma inflamação generalizada da pleura, pericárdio, peritoneu, membranas sinoviais e meninges, acompanhada pela elevada presença de fibrina. HPS é normalmente um agente secundário causado por algum factor predisponente, como stress, pneumonias ou por algum vírus, em particular o Vírus do Síndrome Respiratório e Reprodutor Porcino (PRRSv).No caso das pneumonias verificou-se que o agente HPS é um invasor secundário oportunista e que causa doença em associação com outros agentes víricos ou bacterianos e está associado com maior prevalência de pneumonia por agentes respiratórios víricos, como o Síndrome Respiratório e Reprodutor Porcino (PRRS). Durante este estudo de caso acompanhou-se um lote de leitões desde o desmame até ao final da recria, em que foram feitas serologias e enviados leitões inteiros para laboratório de forma a isolar e identificar o agente. Foi feita a avaliação da morbilidade bem como o cálculo do índice de tosse e taxa de mortalidade nas primeiras quatro semanas de recria. Efectuaram-se necropsias dos leitões deste lote. Pretende-se, como objectivo deste estudo, definir o agente primário causador da patologia, neste caso o PRRSv, bem como a entrada da infecção bacteriana secundária causada pelo HPS. Procedeu-se à vacinação do efectivo frente ao PRRSv. Como profilaxia, devido à falha de protecção de imunidade maternal, fez-se a administração de tulatromicina a todos os leitões até todo o efectivo estar devidamente protegido frente ao PRRSv, conferindo assim uma boa imunidade maternal.The porcine polyserositis complex is caused by multiple factors, particularly by Haemophilus parasuis (HPS), which has been causing several problems in pigs, both at the respiratory and articular levels. HPS is the causative agent of Glässer's Disease (DG), characterized by a generalized inflammation of the pleura, pericardium, peritoneum, synovial membranes and meninges, toguether with an abundant presence of fibrin. HPS is usually a secondary agent enhanced by some predisposing factor, like stress, pneumonia or some viruses, such as Porcine Reproductive and Respiratory Syndrome virus (PRRSv). In pneumonia, it has been show that HPS is an opportunistic secondary invader causing disease in association with other viral or bacterial agents being PRRSv the most prevalent respiratory viral agent found together with HPS. During this study a batch of piglets was followed from weaning until the end of nursery season, when serologies were performed, samples were collected and whole piglets were sent to pathology in order to isolate and identify the agent. Health condition was evaluated as well as the calculation of cough index and mortality rate in the first four weeks of nursery. Necropsies of the piglets of this batch were also carried out.The objective of this study was to define the primary agent causing disease (in this case PRRSv), as well as the factors that predisposed to secondary bacterial infections caused by HPS. Following these findings all herd was vaccinated against PRRSv. Due to lack of protective maternal immunity, tulathromycin was administered in pigs, as prophylactic measure until all sows were adequately protected against PRRSv, thus conferring good maternal immunity to their offspring

NMR spectroscopy of native and in vitro tissues implicates polyADP ribose in biomineralization.

Nuclear magnetic resonance (NMR) spectroscopy is useful to determine molecular structure in tissues grown in vitro only if their fidelity, relative to native tissue, can be established. Here, we use multidimensional NMR spectra of animal and in vitro model tissues as fingerprints of their respective molecular structures, allowing us to compare the intact tissues at atomic length scales. To obtain spectra from animal tissues, we developed a heavy mouse enriched by about 20% in the NMR-active isotopes carbon-13 and nitrogen-15. The resulting spectra allowed us to refine an in vitro model of developing bone and to probe its detailed structure. The identification of an unexpected molecule, poly(adenosine diphosphate ribose), that may be implicated in calcification of the bone matrix, illustrates the analytical power of this approach

What are the financial barriers to medical care among the poor, the sick and the disabled in the Special Administrative Region of China?

Although Hong Kong is one of the richest cities in the world and has some of the best health outcomes such as long life expectancy, little is known about the people who are unable to access healthcare due to lack of financial means. Cross-sectional data from a sample of 2,233 participants aged 18 or above was collected from the first wave of the "Trends and Implications of Poverty and Social Disadvantages in Hong Kong" survey. Socio-demographic factors, lifestyle factors, and physical and mental health conditions associated with people who were unable to seek medical services due to lack of financial means in the past year were examined using forward stepwise logistic regression analyses. Of the 2,233 participants surveyed, 8.4% did not seek medical care due to lack of financial means during the past year. They were more likely to be income-poor. With respect to physical and mental health, despite having less likelihood to have multimorbidity, they tended to have higher levels of both anxiety and stress, poorer physical and mental health-related quality of life, and suffer from more severe disability and pain symptoms affecting their daily activities, when compared to the rest of the Hong Kong population. People who were denied of medical care due to financial barriers are generally sicker than people in the general Hong Kong population, implying that those with greater healthcare needs may have financial difficulties in receiving timely and appropriate medical care. Our findings suggest that inequity in healthcare utilization remains a critical issue in Hong Kong