72 research outputs found

    From Houses to Hillsides: Support for Adaptive Housing on Hong Kong's Slopes

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    Hong Kong’s urban development is governed by the mountainous terrain of the city. The city is growing, and easily developable low-lying flat land is becoming increasingly scarce. As a result, Hong Kong’s development is conflicted between the hillsides of the landscape and the urban built environment. On one hand, the avoidance of hillsides, characterized as liabilities, has created a hyper-dense environment where real estate economics and speculation separate public and private housing sectors with little opportunity for alternative affordable housing options. On the other hand, as urban expansion encroaches ever closer to the slopes of the city, new strategies for slope stabilization infrastructure are required for improved safety and resilience. With no resolution to this spatial struggle, informal settlements arise to create affordability through the absence of formal regulation, but these structures pose psycho-social and physical risks to their inhabitants. Rather than attempting to provide housing in an all-or-nothing manner, we can think of housing as an incremental process where citizens foster their social and economic capital. By acknowledging informality as a process that functions within the market, we break down the legal apartheid between formal and informal, and begin to design with, rather than against, bottom-up approaches to high-density urban living. Through the redesign of slope infrastructure with architectural foundations, and the integration of services and amenities, we plant the seeds for building to occur on a site that would otherwise be avoided by conventional development. Expanding on existing geotechnical and slope landscaping methods, the man-made slope in the Mei Tung Estate in Kowloon is transformed into a support framework acting as both the stabilization for the slope and the foundation for transformative infill housing. It provides the basic services for occupation where homes can grow with participatory design and collective action. This foundation is not only a spot on which residents can build, but as a component of the three-dimensional public realm of the city, it also offers opportunities to foster social capital within the larger Hong Kong society to improve social cohesion and integration. The focus is on providing the architectural framework in which healthy, safe, and economical inhabitant-driven building can occur. Housing is not a product for the inhabitant, but a process in which families can make a place to call home

    Corpus of Mandarin Child Language: a preliminary study on the acquisition of semantic content categories in Mandarin-speaking preschoolers

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    In studying language acquisition in children, sizable research studies have been focusing on the investigation of form and lexical semantics. This study aims to establish a child language database annotated both syntactically with part of speech and semantically with semantic content category to supplement the study of child language acquisition in the semantic domain beyond lexical level. The Corpus of Mandarin Child Language (CMCL) that documented the production of different semantic content categories by Mandarin-speaking children was established. Naturalistic language samples of 82 native Mandarin-speaking children aged 25–60 months, divided into three age groups, were obtained. The corresponding semantic content categories coded in each utterance were tagged according to previous studies, in addition to the annotations of part of speech. MLU and lexical diversity were examined and the usage and acquisition of different semantic content categories were also analyzed. The results regarding syntactic complexity and lexical diversity replicated the typical language acquisition pattern from previous studies, which supported the validity of the data obtained in the CMCL. To investigate the trajectory of acquisition of various semantic content categories by age, a 90% acquisition criterion was used. Our findings regarding the acquisition order of semantic content category were basically in line with previous studies in general, with some minor differences. This acquisition order observed is largely explained by the cognitive and syntactic complexity associated with the semantic content category, with additional influence from language specific properties and cultural specific factors of Mandarin. In addition, with the tags in both part-of-speech and semantic content category, the CMCL potentially provides a platform for examining the form-content interface in early child language acquisition, which also implies significantly on the theoretical and clinical ground

    Identification of microbial community in the urban environment: The concordance between conventional culture and nanopore 16S rRNA sequencing

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    IntroductionMicrobes in the built environment have been implicated as a source of infectious diseases. Bacterial culture is the standard method for assessing the risk of exposure to pathogens in urban environments, but this method only accounts for <1% of the diversity of bacteria. Recently, full-length 16S rRNA gene analysis using nanopore sequencing has been applied for microbial evaluations, resulting in a rise in the development of long-read taxonomic tools for species-level classification. Regarding their comparative performance, there is, however, a lack of information.MethodsHere, we aim to analyze the concordance of the microbial community in the urban environment inferred by multiple taxonomic classifiers, including ARGpore2, Emu, Kraken2/Bracken and NanoCLUST, using our 16S-nanopore dataset generated by MegaBLAST, as well as assess their abilities to identify culturable species based on the conventional culture results.ResultsAccording to our results, NanoCLUST was preferred for 16S microbial profiling because it had a high concordance of dominant species and a similar microbial profile to MegaBLAST, whereas Kraken2/Bracken, which had similar clustering results as NanoCLUST, was also desirable. Second, for culturable species identification, Emu with the highest accuracy (81.2%) and F1 score (29%) for the detection of culturable species was suggested.DiscussionIn addition to generating datasets in complex communities for future benchmarking studies, our comprehensive evaluation of the taxonomic classifiers offers recommendations for ongoing microbial community research, particularly for complex communities using nanopore 16S rRNA sequencing

    A clinicopathological study of non-functioning pituitary neuroendocrine tumours using the World Health Organization 2022 classification

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    BackgroundThe 2022 World Health Organization (WHO) classification of pituitary neuroendocrine tumour (PitNET) supersedes the previous one in 2017 and further consolidates the role of transcription factors (TF) in the diagnosis of PitNET. Here, we investigated the clinical utility of the 2022 WHO classification, as compared to that of 2017, in a cohort of patients with non-functioning PitNET (NF-PitNET).MethodsA total of 113 NF-PitNET patients who underwent resection between 2010 and 2021, and had follow-up at Queen Mary Hospital, Hong Kong, were recruited. Surgical specimens were re-stained for the three TF: steroidogenic factor (SF-1), T-box family member TBX19 (TPIT) and POU class 1 homeobox 1 (Pit-1). The associations of different NF-PitNET subtypes with tumour-related outcomes were evaluated by logistic and Cox regression analyses.ResultsBased on the 2022 WHO classification, the majority of NF-PitNET was SF-1-lineage tumours (58.4%), followed by TPIT-lineage tumours (18.6%), tumours with no distinct lineage (16.8%) and Pit-1-lineage tumours (6.2%). Despite fewer entities than the 2017 classification, significant differences in disease-free survival were present amongst these four subtypes (Log-rank test p=0.003), specifically between SF-1-lineage PitNET and PitNET without distinct lineage (Log-rank test p<0.001). In multivariable Cox regression analysis, the subtype of PitNET without distinct lineage (HR 3.02, 95% CI 1.28-7.16, p=0.012), together with tumour volume (HR 1.04, 95% CI 1.01-1.07, p=0.017), were independent predictors of a composite of residual or recurrent disease.ConclusionThe 2022 WHO classification of PitNET is a clinically useful TF and lineage-based system for subtyping NF-PitNET with different tumour behaviour and prognosis

    Sequential algorithm to stratify liver fibrosis risk in overweight/obese metabolic dysfunction-associated fatty liver disease

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    BackgroundNon-diabetic overweight/obese metabolic dysfunction-associated fatty liver disease (MAFLD) represents the largest subgroup with heterogeneous liver fibrosis risk. Metabolic dysfunction promotes liver fibrosis. Here, we investigated whether incorporating additional metabolic risk factors into clinical evaluation improved liver fibrosis risk stratification among individuals with non-diabetic overweight/obese MAFLD.Materials and methodsComprehensive metabolic evaluation including 75-gram oral glucose tolerance test was performed in over 1000 participants from the New Hong Kong Cardiovascular Risk Factor Prevalence Study (HK-NCRISPS), a contemporary population-based study of HK Chinese. Hepatic steatosis and fibrosis were evaluated based on controlled attenuation parameter and liver stiffness (LS) measured using vibration-controlled transient elastography, respectively. Clinically significant liver fibrosis was defined as LS ≥8.0 kPa. Our findings were validated in an independent pooled cohort comprising individuals with obesity and/or polycystic ovarian syndrome.ResultsOf the 1020 recruited community-dwelling individuals, 312 (30.6%) had non-diabetic overweight/obese MAFLD. Among them, 6.4% had LS ≥8.0 kPa. In multivariable stepwise logistic regression analysis, abnormal serum aspartate aminotransferase (AST) (OR 7.95, p<0.001) and homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.5 (OR 5.01, p=0.008) were independently associated with LS ≥8.0 kPa, in a model also consisting of other metabolic risk factors including central adiposity, hypertension, dyslipidaemia and prediabetes. A sequential screening algorithm using abnormal AST, followed by elevated HOMA-IR, was developed to identify individuals with LS ≥8.0 kPa, and externally validated with satisfactory sensitivity (>80%) and negative predictive value (>90%).ConclusionA sequential algorithm incorporating AST and HOMA-IR levels improves fibrosis risk stratification among non-diabetic overweight/obese MAFLD individuals

    CD9 shapes glucocorticoid sensitivity in pediatric B-cell precursor acute lymphoblastic leukemia

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    Resistance to glucocorticoids (GCs), the common agents for remission induction in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), poses a significant therapeutic hurdle. Therefore, dissecting the mechanisms shaping GC resistance could lead to new treatment modalities. Here, we showed that CD9- BCP-ALL cells were preferentially resistant to prednisone and dexamethasone over other standard cytotoxic agents. Concordantly, we identified significantly more poor responders to the prednisone prephase among BCP-ALL patients with a CD9- phenotype, especially for those with adverse presenting features including older age, higher white cell count and BCR-ABL1. Furthermore, gain- and loss-of-function experiments dictated a definitive functional linkage between CD9 expression and GC susceptibility, as demonstrated by the reversal and acquisition of relative GC resistance in CD9low and CD9high BCP-ALL cells, respectively. Despite physical binding to the GC receptor NR3C1, CD9 did not alter its expression, phosphorylation or nuclear translocation but potentiated the induction of GC-responsive genes in GCresistant cells. Importantly, the MEK inhibitor trametinib exhibited higher synergy with GCs against CD9- than CD9+ lymphoblasts to reverse drug resistance in vitro and in vivo. Collectively, our results elucidate a previously unrecognized regulatory function of CD9 in GC sensitivity, and inform new strategies for management of children with resistant BCP-ALL

    Motivations for Undertaking DNA Sequencing-Based Non-invasive Prenatal Testing for Fetal Aneuploidy: A Qualitative Study with Early Adopter Patients in Hong Kong

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    Background A newly introduced cell-free fetal DNA sequencing based non-invasive prenatal testing (DNA-NIPT) detects Down syndrome with sensitivity of 99% at early gestational stage without risk of miscarriage. Attention has been given to its public health implications; little is known from consumer perspectives. This qualitative study aimed to explore women’s motivations for using, and perceptions of, DNA-NIPT in Hong Kong. Methods and Findings In-depth interviews were conducted with 45 women who had undertaken DNA-NIPT recruited by purposive sampling based on socio-demographic and clinical characteristics. The sample included 31 women identified as high-risk from serum and ultrasound based Down syndrome screening (SU-DSS). Thematic narrative analysis examined informed-decision making of the test and identified the benefits and needs. Women outlined a number of reasons for accessing DNA-NIPT: reducing the uncertainty associated with risk probability-based results from SU-DSS, undertaking DNA-NIPT as a comprehensive measure to counteract risk from childbearing especially at advanced age, perceived predictive accuracy and absence of risk of harm to fetus. Accounts of women deemed high-risk or not high-risk are distinctive in a number of respects. High-risk women accessed DNA-NIPT to get a clearer idea of their risk. This group perceived SU-DSS as an unnecessary and confusing procedure because of its varying, protocol-dependent detection rates. Those women not deemed high-risk, in contrast, undertook DNA-NIPT for psychological assurance and to reduce anxiety even after receiving the negative result from SU-DSS. Conclusions DNA-NIPT was regarded positively by women who chose this method of screening over the routine, less expensive testing options. Given its perceived utility, health providers need to consider whether DNA-NIPT should be offered as part of universal routine care to women at high-risk for fetal aneuploidy. If this is the case, then further development of guidelines and quality assurance will be needed to provide a service suited to patients’ needs.ISSN:1932-620
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