PLASER: Pronunciation Learning via Automatic Speech Recognition

PLASER is a multimedia tool with instant feedback designed to teach English pronunciation for high-school students of Hong Kong whose mother tongue is Cantonese Chinese. The objective is to teach correct pronunciation and not to assess a student's overall pronunciation quality. Major challenges related to speech recognition technology include: allowance for non-native accent, reliable and corrective feedbacks, and visualization of errors

Allogeneic Human Mesenchymal Stem Cell Therapy (Remestemcel-L, Prochymal) as a Rescue Agent for Severe Refractory Acute Graft-versus-Host Disease in Pediatric Patients

AbstractSevere steroid-refractory acute graft-versus-host disease (aGVHD) is related to significant mortality and morbidity after allogeneic stem cell transplantation. Early clinical trials of therapy with human mesenchymal stem cells (hMSCs) in pediatric patients with severe aGVHD resistant to multiple immunosuppressive agents showed promising results. In this study, we evaluated the risk/benefit profile of remestemcel-L (Prochymal), a third-party, off-the-shelf source of hMSCs, as a rescue agent for treatment-resistant aGVHD in pediatric patients. Children with grade B-D aGVHD failing steroids and, in most cases, other immunosuppressive agents were eligible for enrollment. Patients received 8 biweekly i.v. infusions of 2 × 106 hMSCs/kg for 4 weeks, with an additional 4 weekly infusions after day +28 for patients who achieved either a partial or mixed response. The enrolled patients compose a very challenging population with severe disease that was nonresponsive to the standard of care, with 88% of the patients experiencing severe aGVHD (grade C or D). Seventy-five patients (median age, 8 yr; 58.7% male; and 61.3% Caucasian) were treated in this study. Sixty-four patients (85.3%) had received an unrelated hematopoietic stem cell graft, and 28 patients (37.3%) had received a cord blood graft. At baseline, the distribution of aGVHD grades B, C, and D was 12.0%, 28.0%, and 60.0%, respectively. The median duration of aGVHD before enrollment was 30 d (range, 2 to 1639 d), and patients failed a median of 3 immunosuppressive agents. Organ involvement at baseline was 86.7% gastrointestinal, 54.7% skin, and 36.0% liver. Thirty-six patients (48.0%) had 2 organs involved, and 11 patients (14.7%) had all 3 organs involved. When stratified by aGVHD grade at baseline, the rate of overall response (complete and partial response) at day +28 was 66.7% for aGVHD grade B, 76.2% for grade C, and 53.3% for grade D. Overall response for individual organs at day +28 was 58.5% for the gastrointestinal system, 75.6% for skin, and 44.4% for liver. Collectively, overall response at day +28 for patients treated for severe refractory aGVHD was 61.3%, and this response was correlated with statistically significant improved survival at day +100 after hMSC infusion. Patients who responded to therapy by day +28 had a higher Kaplan-Meier estimated probability of 100-d survival compared with patients who did not respond (78.1% versus 31.0%; P < .001). Prochymal infusions were generally well tolerated, with no evidence of ectopic tissue formation

Generation of induced pluripotent stem cell lines from 3 distinct laminopathies bearing heterogeneous mutations in lamin A/C

The term laminopathies defines a group of genetic disorders caused by defects in the nuclear envelope, mostly the lamins. Lamins are the main constituents of the nuclear lamina, a filamentous meshwork associated with the inner nuclear membrane that provides mechanical stability and plays important roles in processes such as transcription, DNA replication and chromatin organization. More than 300 mutations in lamin A/C have been associated with diverse clinical phenotypes, understanding the molecular basis of these diseases may provide a rationale for treating them. Here we describe the generation of induced pluripotent stem cells (iPSCs) from a patient with inherited dilated cardiomiopathy and 2 patients with distinct accelerated forms of aging, atypical Werner syndrome and Hutchinson Gilford progeria, all of which are caused by mutations in lamin A/C. These cell lines were pluripotent and displayed normal nuclear membrane morphology compared to donor fibroblasts. Their differentiated progeny reproduced the disease phenotype, reinforcing the idea that they represent excellent tools for understanding the role of lamin A/C in normal physiology and the clinical diversity associated with these diseases

Promotion of knowledge and awareness of parents in HK about infant oral health care

Aim: To promote the knowledge and awareness of infant oral health (OH) care among Hong Kong parents with children aged 0 to 2 years through an interactive workshop and to evaluate its effectiveness. Methods: Parents were recruited from government-registered childcare centers and private playgroups. Interactive workshops consisted of a 30-minute PowerPoint presentation and 20 minutes of small-group activities, which included infant oral hygiene instruction with custom-made infant dentition models, diet analysis and question-and-answer session. Self-completed questionnaires used to evaluate the knowledge and attitude of parents were distributed before and after the workshops. Scores on general OH knowledge (range=0-18), infant OH knowledge (0-10) and parent’s attitude (0-4) were computed. Scores of at least 70% were considered proficient. Results: Among the 111 participants (aged 26 to 54 years, 64% mothers), 96% had a child aged 0 to 30 months. 30% had their children’s mouth cleaned at least twice a day. Only one participant had brought his/her child to see a dentist. Weaker aspects in parents’ OH knowledge and common misconceptions were identified in the pre-survey. Only 35% identified frequent meals as an increased caries risk; only 59% and 79% identified starchy food and formula milk as cariogenic food respectively. 58% did not know water fluoridation can prevent caries, while 33% of parents pointed out calcium supplement can prevent caries. Before the workshop, 41% had proficient general OH knowledge (mean=11.9) and 16% had proficient infant OH knowledge (mean=4.8). Over half of parents showed positive attitude (mean=3.4). Significant improvements in general OH knowledge (mean=15.6, p<0.001), infant OH knowledge (mean=8.8, p<0.001) and attitude (mean=3.9, p<0.001) were observed. Parents reflected the workshops were useful (94%) and they learned new practices to improve their infants’ OH (95%). Conclusion: Several deficiencies in oral health knowledge and behaviour are identified. The interactive workshops can effectively promote the knowledge and awareness of infant oral health care among parents with children aged 0 to 2 years. Large-scale infant oral health survey is needed. Interactive workshops with longer follow-up periods are recommended. More guidelines can be provided to parents and general dentists for prevention of caries.published_or_final_versio

Outcome of transplantation for acute lymphoblastic leukemia in children with down syndrome

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106900/1/pbc24918.pd

Outcome of Transplantation for Acute Myelogenous Leukemia in Children with Down Syndrome

AbstractData on outcomes of allogeneic transplantation in children with Down syndrome and acute myelogenous leukemia (DS-AML) are scarce and conflicting. Early reports stress treatment-related mortality as the main barrier; a recent case series points to posttransplantation relapse. We reviewed outcome data for 28 patients with DS-AML reported to the Center for International Blood and Marrow Transplant Research between 2000 and 2009 and performed a first matched-pair analysis of 21 patients with DS-AML and 80 non-DS AML controls. The median age at transplantation for DS-AML was 3 years, and almost half of the cohort was in second remission. The 3-year probability of overall survival was only 19%. In multivariate analysis, adjusting for interval from diagnosis to transplantation, risks of relapse (hazard ratio [HR], 2.84; P < .001; 62% versus 37%) and transplant-related mortality (HR, 2.52; P = .04; 24% versus 15%) were significantly higher for DS-AML compared to non-DS AML. Overall mortality risk (HR, 2.86; P < .001; 21% versus 52%) was significantly higher for DS-AML. Both transplant-related mortality and relapse contribute to higher mortality. Excess mortality in DS-AML patients can only effectively be addressed through an international multicenter effort to pilot strategies aimed at lowering both transplant-related mortality and relapse risks

Renal cell carcinoma of native kidney in Chinese renal transplant recipients: a report of 12 cases and a review of the literature

Objectives To present and discuss the epidemiological and clinical aspects, as well as therapeutic options and outcome of de novo renal cell carcinoma (RCC) of the native kidneys in a series of Chinese renal transplant recipients. Patients and Methods A retrospective, cohort study examining all renal transplant recipients with the diagnosis of RCC of native kidney followed up in two major regional hospitals in Hong Kong between January 2000 and December 2009. Clinical data includedage, gender, cause of renal failure, symptoms at presentation, duration of transplantation, immunosuppressive therapy, and history of acquired cystic kidney disease (ACKD). Laboratory, radiographic, operative, and pathology reports were used to assess the tumor extent. Results Among the 1,003 renal transplant recipients recruited, 12 transplant recipients had a nephrectomy for a total of 13 RCC. The prevalence of de novo RCC was 1.3%. The mean age at diagnosis of RCC was 48.4 years, and the median time from transplantation to diagnosis was 6.1 years. ACKD was found in 6 (50%) of the patients. All patients except one were asymptomatic. pT1 disease was found in ten patients with a mean tumor size of 3.2 cm. All patients were treated successfully with radical nephrectomy. After a median follow-up of 38 months, two patients (16.7%) died. One died of sepsis, and the other died of metastatic carcinoma. Conclusions With increasing data showing a better prognosis if RCC is detected early by screening, it is time to consider screening all kidney transplant recipients for ACKD and RCC. © The Author(s) 2011. This article is published with open access at Springerlink.com.published_or_final_versionSpringer Open Choice, 21 Feb 201

Reactivation of Epstein–Barr virus by a dual-responsive fluorescent EBNA1-targeting agent with Zn2+-chelating function

EBNA1 is the only Epstein–Barr virus (EBV) latent protein responsible for viral genome maintenance and is expressed in all EBV-infected cells. Zn2+ is essential for oligomerization of the functional EBNA1. We constructed an EBNA1 binding peptide with a Zn2+ chelator to create an EBNA1-specific inhibitor (ZRL5P4). ZRL5P4 by itself is sufficient to reactivate EBV from its latent infection. ZRL5P4 is able to emit unique responsive fluorescent signals once it binds with EBNA1 and a Zn2+ ion. ZRL5P4 can selectively disrupt the EBNA1 oligomerization and cause nasopharyngeal carcinoma (NPC) tumor shrinkage, possibly due to EBV lytic induction. Dicer1 seems essential for this lytic reactivation. As can been seen, EBNA1 is likely to maintain NPC cell survival by suppressing viral reactivation

Challenges and considerations of applying nature-based solutions in low- and middle-income countries in Southeast and East Asia

Low- and middle-income countries in Southeast and East Asia face a range of challenges related to the rapid pace of urbanisation in the region, the scale of pollution, climate change, loss of ecosystem services and associated difficulties for ecological restoration. Possible pathways towards a more sustainable future lie in the applications of nature-based solutions (NBS). However, there is relatively little literature on the application of NBS in the region, particularly Southeast Asia. In this paper we address this gap by assessing the socio-ecological challenges to the application of NBS in the region – one of the most globally biodiverse. We first provide an overview and background on NBS and its underpinnings in biodiversity and ecosystem services. We then present a typology describing five unique challenges for the application of NBS in the region: (1) Characteristics of urbanisation; (2) Biophysical environmental and climatic context; (3) Environmental risks and challenges for restoration; (4) Human nature relationships and conflicts; and (5) Policy and governance context. Exploiting the opportunities through South-South and North-South collaboration to address the challenges of NBS in Southeast and East Asia needs to be a priority for government, planners and academics.Peer reviewe

ITGAM is associated with disease susceptibility and renal nephritis of systemic lupus erythematosus in Hong Kong Chinese and Thai

ITGAM was recently found to be associated with systemic lupus erythematosus (SLE) in populations of not only European ancestry, but also in Hispanic- and African-Americans, Mexicans and Colombians. The risk alleles in the gene, however, were found to be monomorphic in two Asian populations examined: Japanese and Korean. In this study, using a collection of 910 SLE patients and 2360 controls from Chinese living in Hong Kong, analyzed by both genome-wide association and direct sequencing, we confirmed the association of the same risk alleles in ITGAM with the disease. These findings were further replicated in the Thai population with 278 patients and 383 ethnicity- and geography-matched controls. Subphenotype stratification analyses showed significantly more involvement of the gene in patients with renal nephritis and neurological disorders. Although our results support a pivotal role by rs1143679 (R77H) in disease association, our data also suggests an additional contribution from rs1143683, another non-synonymous polymorphism in this gene (A858V). Therefore, despite the low-allele frequencies of the risk alleles of the gene in our two Asian populations, ITGAM was confirmed to be a risk factor related to disease susceptibility and probably severe manifestations of SLE