11,275 research outputs found
Juvenile chronic arthritis in Chinese children: a review of the local experience
published_or_final_versio
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
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
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
Molecular Diagnosis for Paediatric Genetic Disorders Using Whole Exome Sequencing of the Next Generation Sequencing Technology
Oral PresentationMolecular diagnosis for paediatric genetic diseases is
important for targeted or tailored treatment, more
informative genetic counselling and guiding the families
for prenatal or pre-implantation diagnosis. Traditionally,
linkage analysis using large multiplex families or multiple
families with the same molecular cause is essential and the
process could take years before a diagnosis can be reached.
Candidate gene screening is usually the only method
available for clinical laboratories for genetic diseases in
Hong Kong.
Next generation sequencing technology has virtually
revolutionised the way genetic studies are conducted and
provides opportunities for molecular diagnosis for genetic
disorders that were never available before. With the
possibility of sequencing the whole genome or almost all
the coding exons of the genome, the method does not require
the availability of large, multiple affected families and prior knowledge of candidate causal genes. It can be applied to a
single patient or, as a usual practice, whole genome or whole
exome sequencing for the patient plus parents. For whole
exome sequencing (WES), it usually produces up to 100
million short sequencing reads of usually 100bp long. These
short reads were firstly compared with sequences of a
reference human genome and mapped to genomic regions
from which they were generated. Each position (base pair)
of a coding exon is usually covered with dozens to hundreds
of sequencing reads. Analysing the sequences of these reads
allows for identification of mutations that are different from
the reference sequences. For WES for a single individual, up to 100,000 variants
can be identified, with some of which are common variants
in a population and some of which rare or private. The
population frequencies of these variants are looked up in
public databases such as those from the 1000 Genome
Project or ESP6500, a project that sequenced 6500
individuals in the US. An internal database is also
established with WES data from 200 samples from the local
population. For rare, severe genetic disorders that are likely
to be caused by mutations from a single gene, we can safely
rule out the common (>1% in a population) variants and
only focus on the rare or private variants. The nature of the
mutations, such as with or without amino acid changes,
changes in the open reading frame of the protein, the nature
of the amino acid changes (similarity of the amino acid
changed to), the conservation of this amino acid in different
species, and the function of the gene in relationship to the
disease phenotype, are considered to help pinpoint the
causal mutations. We will present examples on using WES for molecular
diagnosis for paediatric genetic disorders in our
Department. These include detection of de novo mutations
(mutations that are not detected in parents), somatic
mutations and compound heterozygous mutations, and
mutations missed by traditional laboratory testing, which
demonstrated the power of this new technology in providing
accurate molecular diagnosis.published_or_final_versio
Non-destructive testing and evaluation of composite materials/structures: A state-of-the-art review
Composite materials/structures are advancing in product efficiency,
cost-effectiveness and the development of superior specific properties. There
are increasing demands in their applications to load-carrying structures in
aerospace, wind turbines, transportation, and medical equipment, etc. Thus
robust and reliable non-destructive testing (NDT) of composites is essential to
reduce safety concerns and maintenance costs. There have been various NDT
methods built upon different principles for quality assurance during the whole
lifecycle of a composite product. This paper reviews the most established NDT
techniques for detection and evaluation of defects/damage evolution in
composites. These include acoustic emission, ultrasonic testing, infrared
thermography, terahertz testing, shearography, digital image correlation, as
well as X-ray and neutron imaging. For each NDT technique, we cover a brief
historical background, principles, standard practices, equipment and facilities
used for composite research. We also compare and discuss their benefits and
limitations, and further summarise their capabilities and applications to
composite structures. Each NDT technique has its own potential and rarely
achieves a full-scale diagnosis of structural integrity. Future development of
NDT techniques for composites will be directed towards intelligent and
automated inspection systems with high accuracy and efficient data processing
capabilities
Autosomal Dominant Gain-of-function STAT1 Mutation is a Novel Genetic Etiology of Penicillium Marneffei Infection
Symposium / Free Paper 4: ImmunologyConference Theme: Inflammatory Basis of Perinatal and Childhood DiseasesBackground: Penicillium marneffei infection is indigenous to Southeast Asia.
Majority of cases occur in patients with AIDS and secondary immunodeficiencies.
We previously reported 4 HIV-negative children with chronic mucocutaneous
candidiasis (CMC) and severe penicilliosis. Hyper-IgE syndrome was diagnosed
in one of them, but extensive genetic studies on IL12-IFNγ axis, CARD9 and AIRE
were unrevealing for the rest. Recently, STAT1 hyperphosphorylation causing
defective Th1 and Th17 immunity is recognized as a cause of CMC.
Objective: To investigate the genetic and functional defects of STAT1 signaling in
children affected by penicilliosis.
Methods: Targeted sequencing of STAT1 gene or total exome sequencing was
performed in 3 patients with CMC and penicilliosis. PBMCs were isolated from
patients and normal controls. Intracellular STAT1 phosphorylation (pSTAT1)
towards interferon-α and interferon-γ stimulation was evaluated by flow
cytometry. Cytokine production in PBMCs towards PMA and ionomycin stimulation
was assessed. PBMCs were co-cultured with live Candida albicans and
P. marneffei to evaluate interferon-γ response.
Results: Heterozygous STAT1 missense mutations were identified in all 3 patients.
Two mutations were located in the coiled-coil domain (P1 and P2) and one in
the DNA-binding domain (P3). All 3 patients recovered from penicilliosis, but P1
eventually died of fulminant aspergillosis. The percentage of pSTAT1-positive
PBMCs induced by interferon-α and interferon-γ was significantly higher in all
3 patients than normal controls, indicating that they had gain-of-function mutations. PBMCs from all patients displayed defective interferon-γ and
interleukin-17 production towards PMA and PMA plus ionomycin, respectively.
Interferon-γ production induced by C. albicans and P. marneffei in P2 was
significantly lower than normal controls.
Conclusions: For the first time, we demonstrated STAT1 gain-of-function
mutation as an important and novel genetic etiology of invasive mycosis including
penicilliosis and aspergillosis. Penicilliosis should be regarded as an indicator
disease for primary immunodeficiencies in children without HIV infection unless
proven otherwise.published_or_final_versio
Investigation of the dynamics of ionization induced injected electrons under the influence of beam loading effects
In laser-driven wakefield, ionization induced injection is an efficient way to inject electrons in the plasma wave. A detailed study on the beam dynamics under the influence of beam loading effects, which can be controlled by the concentration of nitrogen impurity introduced in the hydrogen gas was conducted. For a specific value of this percentage, the final energy of the high-energy electron bunch becomes nearly independent of the trapped positions, thus leading to a small energy dispersion. We also show that the final beam emittance is mainly determined by the injection process
Computational algebraic methods in efficient estimation
A strong link between information geometry and algebraic statistics is made
by investigating statistical manifolds which are algebraic varieties. In
particular it it shown how first and second order efficient estimators can be
constructed, such as bias corrected Maximum Likelihood and more general
estimators, and for which the estimating equations are purely algebraic. In
addition it is shown how Gr\"obner basis technology, which is at the heart of
algebraic statistics, can be used to reduce the degrees of the terms in the
estimating equations. This points the way to the feasible use, to find the
estimators, of special methods for solving polynomial equations, such as
homotopy continuation methods. Simple examples are given showing both equations
and computations. *** The proof of Theorem 2 was corrected by the latest
version. Some minor errors were also corrected.Comment: 21 pages, 5 figure
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