Human enterovirus 71 and hand, foot and mouth disease

Hand, foot and mouth disease (HFMD) is generally a benign febrile exanthematous childhood disease caused by human enteroviruses. The route of transmission is postulated to be faeco-oral in developing areas but attributed more to respiratory droplet in developed areas. Transmission is facilitated by the prolonged environmental survival of these viruses and their greater resistance to biocides. Serious outbreaks with neurological and cardiopulmonary complications caused by human enterovirus 71 (HEV-71) seem to be commoner in the Asian Pacific region than elsewhere in the world. This geographical predilection is unexplained but could be related to the frequency of intra- and inter-typic genetic recombinations of the virus, the host populations' genetic predisposition, environmental hygiene, and standard of healthcare. Vaccine development could be hampered by the general mildness of the illness and rapid genetic evolution of the virus. Antivirals are not readily available; the role of intravenous immunoglobulin in the treatment of serious complications should be investigated. Monitoring of this disease and its epidemiology in the densely populated Asia Pacific epicentre is important for the detection of emerging epidemics due to enteroviruses. Copyright © 2010 Cambridge University Press.published_or_final_versio

A data-driven approach to preprocessing Illumina 450K methylation array data

As the most stable and experimentally accessible epigenetic mark, DNA methylation is of great interest to the research community. The landscape of DNA methylation across tissues, through development and in disease pathogenesis is not yet well characterized. Thus there is a need for rapid and cost effective methods for assessing genome-wide levels of DNA methylation. The Illumina Infinium HumanMethylation450 (450K) BeadChip is a very useful addition to the available methods for DNA methylation analysis but its complex design, incorporating two different assay methods, requires careful consideration. Accordingly, several normalization schemes have been published. We have taken advantage of known DNA methylation patterns associated with genomic imprinting and X-chromosome inactivation (XCI), in addition to the performance of SNP genotyping assays present on the array, to derive three independent metrics which we use to test alternative schemes of correction and normalization. These metrics also have potential utility as quality scores for datasets.|The standard index of DNA methylation at any specific CpG site is β = M/(M + U + 100) where M and U are methylated and unmethylated signal intensities, respectively. Betas (βs) calculated from raw signal intensities (the default GenomeStudio behavior) perform well, but using 11 methylomic datasets we demonstrate that quantile normalization methods produce marked improvement, even in highly consistent data, by all three metrics. The commonly used procedure of normalizing betas is inferior to the separate normalization of M and U, and it is also advantageous to normalize Type I and Type II assays separately. More elaborate manipulation of quantiles proves to be counterproductive.|Careful selection of preprocessing steps can minimize variance and thus improve statistical power, especially for the detection of the small absolute DNA methylation changes likely associated with complex disease phenotypes. For the convenience of the research community we have created a user-friendly R software package called wateRmelon, downloadable from bioConductor, compatible with the existing methylumi, minfi and IMA packages, that allows others to utilize the same normalization methods and data quality tests on 450K data

Spatial analytical methods for deriving a historical map of physiological equivalent temperature of Hong Kong

Physiological Equivalent Temperature (PET) has been widely used as an indicator for impacts of climate change on thermal comfort of humans. The effects of thermal stress are often examined using longitudinal observational studies over many years. A major problem in retrospective versus prospective studies is that it is not feasible to go back in time to measure historical data not collected in the past. These data must be reconstructed for the baseline period to enable comparative analysis of change and its human impact. This paper describes a systematic method for constructing a PET map using spatial analytical procedures. The procedures involve estimating PET values (based on the RayMan model and four key parameters of temperature, relative humidity, wind velocity, and mean radiant temperature) at a spatially disaggregated level comprising of a grid of 100 m × 100 m cells. The method can be applied to other geographic locations pending availability of basic meteorological and morphological data of the locations.postprin

The role of acculturation in the relationship between self-stigma and psychological distress among Chinese American breast cancer survivors

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this record.Attitudes about breast cancer have improved in the USA, yet stigma is still present in some ethnic and immigrant populations and affecting survivors’ experiences. Chinese American breast cancer survivors report negative beliefs and stigma to be a major stressor; this could result in mental health consequences. We hypothesized that greater self-stigma will be related to greater psychological distress (namely, depressive symptoms, and perceived stress). Furthermore, we expected that the association between self-stigma and psychological distress will be stronger among Chinese American breast cancer survivors who are less acculturated to the USA than those who are highly acculturated. One hundred and thirty-six Chinese American breast cancer survivors completed questionnaires that measured self-stigma, acculturation, depressive symptoms, perceived stress, and demographic information. Hierarchical linear regressions were conducted to examine the main effect of stigma on depressive symptoms and perceived stress, and the moderating effect of acculturation. As predicted, self-stigma was associated with greater depressive symptoms and perceived stress among Chinese American breast cancer survivors, especially those who are less acculturated. Self-stigma may play a part in psychological adjustment among Chinese American breast cancer survivors. Interventions that incorporate techniques to reduce self-stigma could be beneficial for Chinese American breast cancer survivors, especially for those who are less acculturated to American society.Herald Cancer AssociationAmerican Cancer Societ

Clinical application of whole exome sequencing for paediatric undiagnosed diseases in Hong Kong: experience from first sixty cases

Oral Free Paper Session: Oral Presentation 5published_or_final_versio

Promotion of collaboration between medical and dental professionals

Includes bibliographical references (p. 25-26).published_or_final_versio

Genome-Wide DNA Methylation Analysis of Chinese Patients with Systemic Lupus Erythematosus Identified Hypomethylation in Genes Related to the Type I Interferon Pathway

published_or_final_versio

Isolation and characterization of dromedary camel coronavirus UAE-HKU23 from dromedaries of the Middle East: minimal serological cross-reactivity between MERS coronavirus and dromedary camel coronavirus UAE-HKU23

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Access and Unmet Needs of Orphan Drugs in 194 Countries and Six Areas: a Global Policy Review with Content Analysis

Objectives: Three hundred million people living with rare diseases worldwide are disproportionately deprived of in-time diagnosis and treatment compared with other patients. This review provides an overview of global policies that optimize development, licensing, pricing, and reimbursement of orphan drugs. Methods: Pharmaceutical legislation and policies related to access and regulation of orphan drugs were examined from 194 World Health Organization member countries and 6 areas. Orphan drug policies (ODPs) were identified through internet search, emails to national pharmacovigilance centers, and systematic academic literature search. Texts from selected publications were extracted for content analysis. Results: One hundred seventy-two drug regulation documents and 77 academic publications from 162 countries/areas were included. Ninety-two of 200 countries/areas (46.0%) had documentation on ODPs. Thirty-four subthemes from content analysis were categorized into 6 policy themes, namely, orphan drug designation, marketing authorization, safety and efficacy requirements, price regulation, incentives that encourage market availability, and incentives that encourage research and development. Countries/areas with ODPs were statistically wealthier (gross national income per capita = $10 875 vs$3950, P < .001). Country/area income was also positively correlated with the scope of the respective ODP (correlation coefficient = 0.57, P < .001). Conclusions: Globally, the number of countries with an ODP has grown rapidly since 2013. Nevertheless, disparities in geographical distribution and income levels affect the establishment of ODPs. Furthermore, identified policy gaps in price regulation, incentives that encourage market availability, and incentives that encourage research and development should be addressed to improve access to available and affordable orphan drugs

Diagnostic value of whole-exome sequencing in Chinese pediatric-onset neuromuscular patients

BACKGROUND: Neuromuscular disorders (NMDs) comprise a group of heterogeneous genetic diseases with a broad spectrum of overlapping the clinical presentations that makes diagnosis challenging. Notably, the recent introduction of whole-exome sequencing (WES) is introducing rapid changes on the genetic diagnosis of NMDs. We aimed to investigate the diagnostic value of WES for pediatric-onset NMDs. METHODS: We applied integrated diagnostic approach and performed WES in 50 Chinese subjects (30 males, 20 females) with undiagnosed pediatric-onset NMDs despite previous specific tests. The patients were categorized in four subgroups according to phenotyping and investigation findings. Variants on NMDs gene list and open exome analysis for those with initial negative findings were identified. RESULTS: WES identified causative variants in ACTA1 (n = 2), POMT1, COL6A1 (n = 2), MTMR2, LMNA, SELENON, DNM2, TGFB1, MPZ, IGHMBP2, and LAMA2 in 13 patients. Two subjects have variants of uncertain significance (VUSs) in TTN and SCN11A, unlikely to be pathogenic due to incompatible phenotypes. The mean interval time from symptom onset to genetic diagnosis was 10.4 years (range from 1 month to 33 years). The overall diagnostic yield of WES in our cohort was 26%. Open exome analysis was necessary to identify the pathogenic variant in TGFB1 that caused skeletal dysplasia with neuromuscular presentation. CONCLUSION: Our study shows a clear role of WES in the pathway of integrated diagnostic approach to shorten the diagnostic odyssey in patients with rare NMDs