Experimental study on turbulence characteristics of a slot jet impingement on semi-circular surfaces

2005-2006 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Microsatellite instability and mismatch repair gene mutations are common in young colorectal cancer patients in Hong Kong

Conference Theme: Challenges to Specialists in the 21st centurypublished_or_final_versio

INDELseek: Detection Of Complex Insertions And Deletions From Next-generation Sequencing Data

BACKGROUND: Complex insertions and deletions (indels) from next-generation sequencing (NGS) data were prone to escape detection by currently available variant callers as shown by large-scale human genomics studies. Somatic and germline complex indels in key disease driver genes could be missed in NGS-based genomics studies. RESULTS: INDELseek is an open-source complex indel caller designed for NGS data of random fragments and PCR amplicons. The key differentiating factor of INDELseek is that each NGS read alignment was examined as a whole instead of 'pileup' of each reference position across multiple alignments. In benchmarking against the reference material NA12878 genome (n = 160 derived from high-confidence variant calls), GATK, SAMtools and INDELseek showed complex indel detection sensitivities of 0%, 0% and 100%, respectively. INDELseek also detected all known germline (BRCA1 and BRCA2) and somatic (CALR and JAK2) complex indels in human clinical samples (n = 8). Further experiments validated all 10 detected KIT complex indels in a discovery cohort of clinical samples. In silico semi-simulation showed sensitivities of 93.7-96.2% based on 8671 unique complex indels in >5000 genes from dbSNP and COSMIC. We also demonstrated the importance of complex indel detection in accurately annotating BRCA1, BRCA2 and TP53 mutations with gained or rescued protein-truncating effects. CONCLUSIONS: INDELseek is an accurate and versatile tool for complex indel detection in NGS data. It complements other variant callers in NGS-based genomics studies targeting a wide spectrum of genetic variations.published_or_final_versio

Identification of five novel WASP mutations in Chinese families with Wiskott-Aldrich syndrome.

The Wiskott-Aldrich Syndrome (WAS) is an X-linked recessive immunodeficiency caused by mutation in the gene encoding WAS protein (WASP). The disease is characterized by eczema, thrombocytopenia and severe immunodeificency and is associated with extensive clinical heterogeneity. Mutation studies indicated that the mutated genotypes are also highly variable. In this study, we performed PCR-direct sequencing analysis of the WAS gene in six unrelated Chinese families. Five novel mutations identified, included two nonsense mutations (506C-->T, 1388-->T), a small insertion (685-686insCGCA) and two single-base deletions (384delT, 984delC). All of the mutations are predicted to lead to premature translational termination of WASP. Copyright 2002 Wiley-Liss, Inc.postprin

Vaccines for prophylaxis of viral infections in patients with hematological malignancies.

Viral infections cause significant morbidity and mortality in patients with hematological malignancies. It remains uncertain whether viral vaccinations in these patients are supported by good evidence. We aimed to determine the effectiveness and safety of viral vaccines in patients with hematological malignancies. We searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL (June 2010), reference lists of relevant papers, abstracts from scientific meetings and contacted vaccine manufacturers. Randomized controlled trials (RCTs) evaluating viral vaccines in patients with hematological malignancies were included. Relative risk (RR) was used for binary data and mean difference (MD) for continuous data. Primary outcome was incidence of infection. Secondary outcomes were mortality, incidence of complications and severe viral infection, hospitalization, immune response and adverse effects. Fixed-effect model was used in meta-analyses. Eight RCTs were included, with 305 patients in the intervention groups and 288 in the control groups. They evaluated heat-inactivated varicella zoster virus (VZV) vaccine (two trials), influenza vaccines (five trials) and inactivated poliovirus vaccine (IPV) (one trial). Seven trials had high and one trial had moderate risk of bias.VZV vaccine might reduce herpes zoster compared to no vaccine (RR 0.54, 95% CI 0.3 to 1.0, P=0.05), but not statistically significant. Vaccination also demonstrated efficacy in immune response but frequently caused local adverse effects. One trial reported severity score of zoster, which favored vaccination (MD 2.6, 95% CI 0.94 to 4.26, P=0.002).Two RCTs compared inactivated influenza vaccine with no vaccine and reported lower risk of lower respiratory infections (RR 0.39, 95% CI 0.19 to 0.78, P=0.008) and hospitalization (RR 0.17, 95% CI 0.09 to 0.31, P<0.00001) in vaccine recipients. However, vaccine recipients more frequently experienced irritability and local adverse effects. There was no significant difference in seroconversion between one and two doses of influenza vaccine (one trial), or between recombinant and standard influenza vaccine (one trial), or influenza vaccine given with or without re-induction chemotherapy (one trial).The IPV trial comparing vaccination starting at 6 versus 18 months after stem cell transplant (SCT) found no significant difference in seroconversion. Inactivated VZV vaccine might reduce zoster severity in adult SCT recipients. Inactivated influenza vaccine might reduce respiratory infections and hospitalization in adults with multiple myeloma or children with leukemia or lymphoma. However, the quality of evidence is low. Local adverse effects occur frequently. Further high-quality RCTs are needed.link_to_subscribed_fulltex

Primary immunodeficiency in Hong Kong and the use of genetic analysis for diagnosis

Objectives. To review the management of primary immunodeficiency and discuss recent advances in genetic analysis. Design. Retrospective study. Setting. University teaching hospital, Hong Kong. Patients. Children diagnosed with primary immunodeficiency and followed up in the immunology clinic during the period 1988 to 2003. Main outcome measures. Demographic data, co-morbidities and treatment of patients, outcome and complications; identification of disease by genetic mutations. Results. Medical records of a total of 117 patients (72 male, 45 female) diagnosed with primary immunodeficiency in the Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, Hong Kong during the past 15 years (1988-2003) were reviewed. All patients were followed up in the immunology clinic. Some patients had been referred from the private sector or other hospitals for immunological workup. Six categories of primary immunodeficiency were identified: predominantly humoral defect (n=50), predominantly cellular defect (n=22), combined humoral and cellular defect (n=5), phagocytic defect (n=18), complement disorders (n=4), and others (n=18). Although infection was the underlying cause of most co-morbidities and mortality, autoimmune (n=7) and allergic (n=23) manifestations were common. In addition, three patients developed lymphoma. Recent advances in the genetic diagnosis of several types of primary immunodeficiency were also reviewed: X-linked Wiskott-Aldrich syndrome, X-linked chronic granulomatous disease, X-linked agammaglobulinaemia, X-linked lymphoproliferative syndrome, leukocyte adhesion disease type I, and X-linked hyperimmunoglobulin M syndrome. This provides an invaluable means of understanding the molecular basis of primary immunodeficiency and has important clinical applications. Conclusions. Co-morbidities like autoimmune disease and allergic disease are common in patients with primary immunodeficiency and should be carefully evaluated. Likewise, a diagnosis of primary immunodeficiency should be considered when evaluating patients with these conditions. Rapid progress in the field of molecular genetics will enable definite and early diagnosis, and more importantly, potential curative therapy to be administered.published_or_final_versio

Human oropharynx as natural reservoir of Streptobacillus hongkongensis

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MSH2 c.1452-1455delAATG Is a Founder Mutation and an Important Cause of Hereditary Nonpolyposis Colorectal Cancer in the Southern Chinese Population

Hereditary nonpolyposis colorectal cancer (HNPCC) accounts for ∼2% of all colorectal cancer (CRC) cases and is the most common hereditary CRC syndrome. We have previously reported a high incidence of microsatellite instability (MSI) and germline mismatch repair (MMR) gene mutations in young Hong Kong Chinese with CRC. Ongoing studies at the Hereditary Gastrointestinal Cancer Registry in Hong Kong have revealed a unique germline MSH2 c.1452-1455delAATG mutation that has not been reported in other ethnic groups. Detailed analysis showed that this specific MSH2 mutation constituted 21% of all germline MMR gene mutations and 36% of all MSH2 germline mutations identified. We designed a specific PCR-based diagnostic test on paraffin-embedded tissues and identified this germline mutation in 2 1.5%) of 138 consecutive patients with early-onset CRC (93 million. Further analysis suggested that this founder mutation may date back to between 22 and 103 generations ago. The identification of this MSH2 founder mutation has important implications for the design of mutation-detection strategies for the southern Chinese population. Since there were major emigrations from Hong Kong and Guangdong province during the 19th and 20th centuries, this finding is also significant for Chinese communities worldwide.published_or_final_versio

Port spatial development and theory of constraints

Author name used in this publication: Tsz Leung YipRefereed conference paper2010-2011 > Academic research: refereed > Refereed conference paperVersion of RecordPublishe

Identification of BRCA1/2 germline mutations by integrated approach

This journal suppl. entitled: Primary Therapy of Early Breast Cancer: 14th St.Gallen International Breast Cancer ConferencePoster Presentation: P140postprin