Perception of urban park soundscape

A number of studies have been initiated to explore how to improve the soundscape quality in urban parks. However, good soundscape quality in parks cannot be provided without a thorough understanding of the complex relationships among sound, environment, and individuals. As acoustic comfort is considered to be an important outcome of soundscape quality, this study investigates the relative impacts of the factors influencing acoustic comfort evaluation by formulating a multivariate ordered logit model. This study also explores the inter-relationships among acoustic comfort evaluation, acceptability of the environment, and preference to stay in a park using a path model. A total of 595 valid responses were obtained from interview surveys administered in four parks in Hong Kong while objective sound measurements were carried out at the survey spots concurrently. The findings unveil that acoustic comfort evaluation, besides visual comfort evaluation of landscape, also plays an important role on users’ acceptability of the urban park environment. Compared with all the studied acoustic related factors, acoustic comfort evaluation serves as a better proxy for park users’ preference to stay in urban parks. Hearing the breeze will significantly increase the likelihood of individuals in giving high acoustic comfort evaluation. Conversely, hearing the sounds from heavy vehicles or sounds from bikes will significantly reduce the likelihood in giving a high acoustic evaluation.Department of Building Services EngineeringDepartment of Mechanical Engineerin

Perception of urban park soundscape

A number of studies have been initiated to explore how to improve the soundscape quality in urban parks. However, good soundscape quality in parks cannot be provided without a thorough understanding of the complex relationships among sound, environment, and individuals. As acoustic comfort is considered to be an important outcome of soundscape quality, this study investigates the relative impacts of the factors influencing acoustic comfort evaluation by formulating a multivariate ordered logit model. This study also explores the inter-relationships among acoustic comfort evaluation, acceptability of the environment, and preference to stay in a park using a path model. A total of 595 valid responses were obtained from interview surveys administered in four parks in Hong Kong while objective sound measurements were carried out at the survey spots concurrently. The findings unveil that acoustic comfort evaluation, besides visual comfort evaluation of landscape, also plays an important role on users' acceptability of the urban park environment. Compared with all the studied acoustic related factors, acoustic comfort evaluation serves as a better proxy for park users' preference to stay in urban parks. Hearing the breeze will significantly increase the likelihood of individuals in giving high acoustic comfort evaluation. Conversely, hearing the sounds from heavy vehicles or sounds from bikes will significantly reduce the likelihood in giving a high acoustic evaluation

Non-mitotic proliferation of malignant cancer cells revealed through live-cell imaging of primary and cell-line cultures

Abstract Introduction Anti-mitosis has been a key strategy of anti-cancer therapies, targeting at a fundamental property of cancer cells, their non-controllable proliferation due to overactive mitotic divisions. For improved anti-cancer therapies, it is important to find out whether cancer cells can proliferate independent of mitosis and become resistant to anti-mitotic agents. Results In this study, live-cell imaging was applied to both primary-cultures of tumor cells, and immortalized cancer cell lines, to detect aberrant proliferations. Cells isolated from various malignant tumors, such as Grade-III hemangiopericytoma, atypical meningioma, and metastatic brain tumor exhibit distinct cellular behaviors, including amoeboid sequestration, tailing, tunneling, nucleic DNA leakage, as well as prokaryote-like division such as binary fission and budding-shedding, which are collectively referred to and reported as ‘non-mitotic proliferation’ in this study. In contrast, benign tumors including Grade-I hemangiopericytoma and meningioma were not obvious in such behaviors. Moreover, when cultured in medium free of any anti-cancer drugs, cells from a recurrent Grade-III hemangiopericytoma that had been subjected to pre-operation adjuvant chemotherapy gradually shifted from non-mitotic proliferation to abnormal mitosis in the form of daughter number variation (DNV) and endomitosis, and eventually regular mitosis. Similarly, when treated with the anti-cancer drugs Epirubicin or Cisplatin, the cancer cell lines HeLa and A549 showed a shift from regular mitosis to abnormal mitosis, and further to non-mitosis as the dominant mode of proliferation with increasing drug concentrations. Upon removal of the drugs, the cells reversed back to regular mitosis with only minor occurrences of abnormal mitosis, accompanied by increased expression of the stem cell markers ALDH1, Sox, Oct4 and Nanog. Conclusions The present study revealed that various types of malignant, but not benign, cancer cells exhibited cellular behaviors indicative of non-mitotic proliferation such as binary fission, which was typical of prokaryotic cell division, suggesting cell level atavism. Moreover, reversible transitions through the three modes of proliferation, i.e., mitosis, abnormal mitosis and non-mitosis, were observed when anticancer drug concentrations were grossly increased inducing non-mitosis or decreased favoring mitosis. Potential clinical significance of non-mitotic proliferation in cancer drug resistance and recurrence, and its relationship with cancer stem cells are worthy of further studies

RNF43 germline and somatic mutation in serrated neoplasia pathway and its association with BRAF mutation

OBJECTIVE: Serrated polyps (hyperplastic polyps, sessile or traditional serrated adenomas), which can arise in a sporadic or polyposis setting, predispose to colorectal cancer (CRC), especially those with microsatellite instability (MSI) due to MLH1 promoter methylation (MLH1(me+)). We investigate genetic alterations in the serrated polyposis pathway. DESIGN: We used a combination of exome sequencing and target gene Sanger sequencing to study serrated polyposis families, sporadic serrated polyps and CRCs, with validation by analysis of The Cancer Genome Atlas (TCGA) cohort, followed by organoid-based functional studies. RESULTS: In one out of four serrated polyposis families, we identified a germline RNF43 mutation that displayed autosomal dominant cosegregation with the serrated polyposis phenotype, along with second-hit inactivation through loss of heterozygosity or somatic mutations in all serrated polyps (16), adenomas (5) and cancer (1) examined, as well as coincidental BRAF mutation in 62.5% of the serrated polyps. Concurrently, somatic RNF43 mutations were identified in 34% of sporadic sessile/traditional serrated adenomas, but 0% of hyperplastic polyps (p=0.013). Lastly, in MSI CRCs, we found significantly more frequent RNF43 mutations in the MLH1(me+) (85%) versus MLH1(me-) (33.3%) group (p<0.001). These findings were validated in the TCGA MSI CRCs (p=0.005), which further delineated a significant differential involvement of three Wnt pathway genes between these two groups (RNF43 in MLH1(me+); APC and CTNNB1 in MLH1(me-)); and identified significant co-occurrence of BRAF and RNF43 mutations in the MSI (p<0.001), microsatellite stable (MSS) (p=0.002) and MLH1(me+) MSI CRCs (p=0.042). Functionally, organoid culture of serrated adenoma or mouse colon with CRISPR-induced RNF43 mutations had reduced dependency on R-spondin1. CONCLUSIONS: These results illustrate the importance of RNF43, along with BRAF mutation in the serrated neoplasia pathway (both the sporadic and familial forms), inform genetic diagnosis protocol and raise therapeutic opportunities through Wnt inhibition in different stages of evolution of serrated polyps

Mitochondrial diseases in Hong Kong: prevalence, clinical characteristics and genetic landscape

Abstract Objective To determine the prevalence of mitochondrial diseases (MD) in Hong Kong (HK) and to evaluate the clinical characteristics and genetic landscape of MD patients in the region. Methods This study retrospectively reviewed the phenotypic and molecular characteristics of MD patients from participating public hospitals in HK between January 1985 to October 2020. Molecularly and/or enzymatically confirmed MD cases of any age were recruited via the Clinical Analysis and Reporting System (CDARS) using relevant keywords and/or International Classification of Disease (ICD) codes under the HK Hospital Authority or through the personal recollection of treating clinicians among the investigators. Results A total of 119 MD patients were recruited and analyzed in the study. The point prevalence of MD in HK was 1.02 in 100,000 people (95% confidence interval 0.81–1.28 in 100,000). 110 patients had molecularly proven MD and the other nine were diagnosed by OXPHOS enzymology analysis or mitochondrial DNA depletion analysis with unknown molecular basis. Pathogenic variants in the mitochondrial genome (72 patients) were more prevalent than those in the nuclear genome (38 patients) in our cohort. The most commonly involved organ system at disease onset was the neurological system, in which developmental delay, seizures or epilepsy, and stroke-like episodes were the most frequently reported presentations. The mortality rate in our cohort was 37%. Conclusion This study is a territory-wide overview of the clinical and genetic characteristics of MD patients in a Chinese population, providing the first available prevalence rate of MD in Hong Kong. The findings of this study aim to facilitate future in-depth evaluation of MD and lay the foundation to establish a local MD registry