Information seeking behavior of police officers in Hong Kong: an exploratory study

Open URL - http://www.academic-conferences.org/pdfs/ICICKM10-Booklet.pdfThe information seeking behavior of a random sample of 40 Hong Kong Police Force (HKPF) officers was investigated from the perspectives of: information seeking behavior; type of searching undertaken; level of sophistication of searching; ability to retrieve required information, and use of the HKPF Library (HKPFL). Frameworks such as: the information seeking process (Chowdhury 2004); the information management cycle (Choo, 1998); and the Information seeking of professionals model (Leckie, Pettigrew & Sylvain 1996), were applied. Data gathering methods included: survey; interview; observation; and case study. Results indicate that the respondents are not, overall, effective information seekers. The respondents generally apply simple retrieval techniques despite perceiving them to be less effective than more advanced techniques. The respondents were often unable to effectively frame simple enquiries. A novice member was less effective and slower at retrieving information than an experienced member, suggesting that transfer of organizational members’ knowledge of information seeking to newer members could be valuable. The sampled HKPF members prefer using print materials to electronic materials or web pages, although these formats are also popular. 27 (67.5%) respondents visit the HKPFL two or less times per week, while 36 (90%) respondents visit the HKPFL website two or less times per week. Most respondents use the HKPFL for leisure rather than work related purposes, although this behavior is both position and department sensitive. Most respondents prefer to browse the collections on shelves and seek help from librarians instead of searching the library catalogue. Recommendations for improving HKPF members’ information skills include: information literacy instruction for new recruits; promoting the HKPFL as an information hub; providing guides for use; and further developing the HKPFL to match members’ information needs by improving collections.published_or_final_versionThe 7th International Conference on Intellectual Capital, Knowledge Management & Organisational Learning (ICICKM 2010), Hong Kong, China, 11-12 November 2010. In Proceedings of 7th ICICKM, 2010, p. 11-1

Identification of SCN1A and PCDH19 mutations in Chinese children with Dravet syndrome

Background: Dravet syndrome is a severe form of epilepsy. Majority of patients have a mutation in SCN1A gene, which encodes a voltage-gated sodium channel. A recent study has demonstrated that 16% of SCN1A-negative patients have a mutation in PCDH19, the gene encoding protocadherin-19. Mutations in other genes account for only a very small proportion of families. TSPYL4 is a novel candidate gene within the locus 6q16.3-q22.31 identified by linkage study. Objective: The present study examined the mutations in epileptic Chinese children with emphasis on Dravet syndrome. Methods: A hundred children with severe epilepsy were divided into Dravet syndrome and non-Dravet syndrome groups and screened for SCN1A mutations by direct sequencing. SCN1A-negative Dravet syndrome patients and patients with phenotypes resembling Dravet syndrome were checked for PCDH19 and TSPYL4 mutations. Results: Eighteen patients (9 males, 9 females) were diagnosed to have Dravet syndrome. Among them, 83% (15/18) had SCN1A mutations including truncating (7), splice site (2) and missense mutations (6). The truncating/splice site mutations were associated with moderate to severe degree of intellectual disability (p<0.05). During the progression of disease, 73% (11/15) had features fitting into the diagnostic criteria of autism spectrum disorder and 53% (8/15) had history of vaccination-induced seizures. A novel PCDH19 p.D377N mutation was identified in one SCN1A-negative female patient with Dravet syndrome and a known PCDH19 p.N340S mutation in a female non-Dravet syndrome patient. The former also inherited a TSPYL4 p.G60R variant. Conclusion: A high percentage of SCN1A mutations was identified in our Chinese cohort of Dravet syndrome patients but none in the rest of patients. We demonstrated that truncating/splice site mutations were linked to moderate to severe intellectual disability in these patients. A de novo PCDH19 missense mutation together with an inherited TSPYL4 missense variant were identified in a patient with Dravet syndrome. © 2012 Kwong et al.published_or_final_versio

Histological regression of squamous esophageal carcinoma assessed by percentage of residual viable cells after neoadjuvant chemoradiation is an important prognostic factor

Background: Whether the TNM staging system is applicable after neoadjuvant chemoradiation in esophageal cancer is controversial. The aim of this study was to evaluate the prognostic value of histopathological regression of the primary tumor in postchemoradiated patients. Materials and Methods: The pretherapeutic and pathological ypTNM stages of patients who have had neoadjuvant chemoradiation followed by esophagectomy were analyzed. The percentage of residual viable cells of the primary tumor (ypV) and other clinicopathological factors were tested for their prognostic value. Results: Of 175 recruited patients, 55 (31.4%) achieved pathological complete response. The median survival of these 55 patients was significantly longer than those with other disease stages (124.8 vs 21.1 months) (P <.001). Gender, ypT, ypN, ypTNM, and ypV stage were significant prognostic factors in univariate analysis. In patients without nodal metastases, the median survival in patients with residual viable cells in the primary tumor (ypV?) was 24.6 months, compared with that of 124.8 months in those with no viable cells (ypV0) (P =.043). In those who had nodal metastases, the median survival of patients with ypV0 and ypV? were 21.2 months and 17.4 months respectively (P =.37). Cox regression analysis showed that male gender, high percentage of residual viable cells (ypV), and positive nodal status (ypN1) were independent predictors of poor prognosis. Conclusions: In patients who underwent neoadjuvant chemoradiation therapy, histopathological regression of the primary tumor indicated by percentage of residual viable cells is an important prognostic factor in addition to nodal status and gender. © The Author(s) 2010.published_or_final_versionSpringer Open Choice, 01 Dec 201

Anti-cancer effects of a novel quinoline derivative 83b1 on human esophageal squamous cell carcinoma through Down-Regulation of COX-2 mRNA and PGE2

published_or_final_versio

Key exploited species as surrogates for coastal conservation in an oceanic archipelago: insights from topshells and limpets from Madeira (NE Atlantic Ocean)

As lapas e os caramujos estão entre os herbívoros mais bem adaptados ao intertidal do Atlântico Nordeste. Estas espécies-chave fornecem serviços ecossistémicos valiosos, desempenhando um papel fundamental no equilíbrio ecológico do intertidal e têm um elevado valor económico, estando sujeitas a altos níveis de exploração e representando uma das atividades económicas mais rentáveis na pesca de pequena escala no arquipélago da Madeira. Esta dissertação visa preencher as lacunas existentes na história de vida e dinâmica populacional destas espécies, e aferir os efeitos da regulamentação da apanha nos mananciais explorados. A abordagem conservacionista implícita ao longo desta tese pretende promover: (i) a regulamentação adequada da apanha de caramujos (Phorcus sauciatus) e (ii) a avaliação dos efeitos da regulamentação da apanha de lapas nas populações exploradas (Patella aspera, Patella candei). Atualmente, os mananciais de lapas e caramujos são explorados perto do rendimento máximo sustentável, e a monitorização e fiscalização são fundamentais para evitar a futura sobre-exploração. A regulamentação da apanha de lapas produziu um efeito positivo nas espécies de lapas exploradas, com um aumento no tamanho, na proporção de indivíduos reprodutores, no tamanho de maturação e num maior equilíbrio na proporção de sexos. A apanha de caramujos não está regulamentada e com o atual nível de exploração ocorrem alterações na estrutura de tamanhos, abundância e potencial reprodutivo das populações exploradas, pelo que urge implementar a regulamentação da apanha desta espécie, por forma a mitigar os efeitos negativos desta atividade. O efeito da proximidade das populações humanas e acessibilidade costeira na estrutura de tamanhos e abundância de gastrópodes explorados mostrou que a proporção de reprodutores e a abundância eram geralmente menores em áreas mais próximas das populações humanas e em áreas mais acessíveis. Os efeitos das Áreas Marinhas Protegidas na proteção das populações de lapas resultaram num aumento diferencial do tamanho, da maturidade sexual e da captura por unidade de esforço de acordo com o grau de proteção. O esclarecimento e envolvimento das comunidades locais, reguladores, decisores políticos e partes interessadas, baseados em informação e educação, são cruciais para uma gestão eficaz e sustentável destes gastrópodes marinhos e ecossistemas a médio e longo prazo.Limpets and topshells are among the most successful intertidal grazers in the North-eastern Atlantic. These keystone species play a pivotal role in structuring rocky shores communities, and provoding valuable ecosystem services. Than have an important economic value, being subject to high levels of exploitation and representing one of the most profitable economic activities in small-scale fisheries in the archipelago of Madeira. This thesis aims to fill the gaps on the life-traits and population dynamics of these species, and assess the effects of harvesting regulations on the exploited stocks. A focus on conservation is implicit throughout this thesis since it addresses the promotion of: (i) proper regulation of the unregulated harvesting of topshells (Phorcus sauciatus) and (ii) provide additional information on the effects of harvesting regulations on limpets (Patella aspera, Patella candei). Currently, limpets and topshells stocks are being exploited near the maximum sustainable yield and monitoring and enforcement must be accomplished to avoid future overexploitation. Conservation measures prompted a positive effect on both exploited limpet species with an increase in length, reproductive individuals, size-at-first maturity and a more balanced sex-ratio after harvesting regulations. The harvesting of topshells is not regulated and with the current level of exploitation there are changes in the size structure, abundance and reproductive potential of the exploited populations, so it is imperative to implement the harvesting regulations for this species, in order to mitigate the negative effects of harvesting. The effect of proximity to human settlements and coastal accessibility on the size-structure and abundance of exploited gastropods showed that the mean-size, proportion of reproductive individuals and abundance were generally smaller in areas closer to human settlements and in more accessible areas. The effects of protection from the Marine Protected Areas on limpet populations resulted in a differential increase on size, size-at-first maturity and catch-per-unit-effort according to the degree of protection. The understanding and commitment of local communities, regulators, policymakers and stakeholders, based on information and education are crucial to the effective management and to ensure the sustainability of these marine gastropods and ecosystems at medium and long term

Targeting VEGFR-1 and VEGFR2-expressing non-tumor cells is essential for esophageal cancer therapy

Increasing appreciation of tumor heterogeneity and the tumor-host interaction has stimulated interest in developing novel therapies that target both tumor cells and tumor microenvironment. Bone marrow derived cells (BMDCs) constitute important components of the tumor microenvironment. In this study, we aim to investigate the significance of VEGFR1- and VEGFR2-expressing non-tumor cells, including BMDCs, in esophageal cancer (EC) progression and in VEGFR1/VEGFR2-targeted therapies. Here we report that VEGFR1 or VEGFR2 blockade can significantly attenuate VEGF-induced Src and Erk signaling, as well as the proliferation and migration of VEGFR1+ and VEGFR2+ bone marrow cells and their pro-invasive effect on cancer cells. Importantly, our in vivo data show for the first time that systemic blockade of VEGFR1+ or VEGFR2+ non-tumor cells with neutralizing antibodies is sufficient to significantly suppress esophageal tumor growth, angiogenesis and metastasis in mice. Moreover, our tissue microarray study of human EC clinical specimens showed the clinicopathological significance of VEGFR1 and VEGFR2 in EC, which suggest that anti-VEGFR1/VEGFR2 therapies may be particularly beneficial for patients with aggressive EC. In conclusion, this study demonstrates the important contributions of VEGFR1+ and VEGFR2+ non-tumor cells in esophageal cancer progression, and substantiates the validity of these receptors as therapeutic targets for this deadly disease.published_or_final_versio

Nuclear Localization of DNAJB6 is Associated with Survival of Patients with Esophageal Cancer and Reduces AKT Signaling and Proliferation of Cancer Cells

Abstract BACKGROUND & AIMS: The DnaJ (Hsp40) homolog, subfamily B, member 6 (DNAJB6) is part of a family of proteins that regulate chaperone activities. One of its isoforms, DNAJB6a, contains a nuclear localization signal and regulates β-catenin signaling during breast cancer development. We investigated the role of DNAJB6 in pathogenesis of esophageal squamous cell carcinoma (ESCC). METHODS: We performed immunohistochemical analyses of primary ESCC samples and lymph node metastases from a cohort of 160 patients, who underwent esophagectomy with no pre-operative chemo-radiotherapy at Hong Kong Queen Mary Hospital. Data were collected on patient outcomes over a median time of 12.1±2.9 months. Retrospective survival association analyses were performed. Wild-type and mutant forms of DNAJB6a were overexpressed in cancer cell lines (KYSE510, KYSE 30TSI, KYSE140, and KYSE70TS), which were analyzed in proliferation and immunoblot assays, or injected subcutaneously into nude mice. Levels of DNAJB6 were knocked down in ESCC cell lines (KYSE450 and T.Tn), immortalized normal esophageal epithelial cell lines (NE3 and NE083), and other cells with short hairpin RNAs or by genome engineering. Bimolecular fluorescence complementation was used to study interactions between proteins in living cells. RESULTS: In primary ESCC samples, patients whose tumors had high nuclear levels of DNAJB6 had longer overall survival times (19.2±1.8 months; 95% confidence interval [CI], 15.6-22.8 months) than patients whose tumors had low nuclear levels of DNAJB6 (12.6±1.4 months; 95% CI, 9.8-15.4 months; P=.004, by log rank test). Based on Cox regression analysis, patients whose tumors had high nuclear levels of DNAJB6 had a lower risk of death than those with low levels (hazard ratio=0.562; 95% CI, 0.379-0.834; P=.004). Based on log rank analysis and Cox regression analysis, the combination of nuclear level of DNAJB6 and the presence of lymph node metastases at diagnosis could be used to stratify patients into groups with good or bad outcomes (P<.0005 for both analyses). There was a negative association between the nuclear level of DNAJB6 and the presence of lymph node metastases (P=.022; Pearson χ2 test). Cancer cell lines that overexpressed DNAJB6a formed tumors more slowly in nude mice than control cells or cells that expressed a mutant form of DNAJB6a that did not localize to the nucleus. DNAJB6 knockdown in cancer cell lines promoted their growth as xenograft tumors in mice. A motif of histidine, proline, and aspartic acid (HPD) in the J domain of DNAJB6a was required for its tumor suppressive effects and signaling via AKT1. Loss of DNAJB6a resulted in upregulation of AKT signaling in cancer cell lines and immortalized esophageal epithelial cells. Expression of a constitutively active form of AKT1 restored proliferation to tumor cells that overexpressed DNAJB6a, and DNAJB6a formed a complex with AKT1 in living cells. Expression of DNAJB6a reduced the sensitivity of ESCC to AKT inhibitors; the expression level of DNAJB6a affected AKT signaling in multiple cancer cell lines. CONCLUSIONS: Nuclear localization of DNAJB6 is associated with longer survival times of patients with ESCC. DNAJB6a reduces AKT signaling, and DNAJB6 expression in cancer cells reduces their proliferation and growth of xenograft tumors in mice. DNAJB6a might be developed as biomarker for progression of ESCC.postprin

Large-scale plasma proteomic profiling identifies a high-performance biomarker panel for Alzheimer's disease screening and staging

INTRODUCTION: Blood proteins are emerging as candidate biomarkers for Alzheimer's disease (AD). We systematically profiled the plasma proteome to identify novel AD blood biomarkers and develop a high-performance, blood-based test for AD. METHODS: We quantified 1160 plasma proteins in a Hong Kong Chinese cohort by high-throughput proximity extension assay and validated the results in an independent cohort. In subgroup analyses, plasma biomarkers for amyloid, tau, phosphorylated tau, and neurodegeneration were used as endophenotypes of AD. RESULTS: We identified 429 proteins that were dysregulated in AD plasma. We selected 19 “hub proteins” representative of the AD plasma protein profile, which formed the basis of a scoring system that accurately classified clinical AD (area under the curve = 0.9690–0.9816) and associated endophenotypes. Moreover, specific hub proteins exhibit disease stage-dependent dysregulation, which can delineate AD stages. DISCUSSION: This study comprehensively profiled the AD plasma proteome and serves as a foundation for a high-performance, blood-based test for clinical AD screening and staging

Whole-exome sequencing reveals critical genes underlying metastasis in oesophageal squamous cell carcinoma

Oesophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers, owing to a high frequency of metastasis. However, little is known about the genomic landscape of metastatic ESCC. To identify the genetic alterations that underlie ESCC metastasis, whole-exome sequencing was performed for 41 primary tumours and 15 lymph nodes (LNs) with metastatic ESCCs. Eleven cases included matched primary tumours, synchronous LN metastases, and non-neoplastic mucosa. Approximately 50–76% of the mutations identified in primary tumours appeared in the synchronous LN metastases. Metastatic ESCCs harbour frequent mutations of TP53, KMT2D, ZNF750, and IRF5. Importantly, ZNF750 was recurrently mutated in metastatic ESCC. Combined analysis from current and previous genomic ESCC studies indicated more frequent ZNF750 mutation in diagnosed cases with LN metastasis than in those without metastasis (14% versus 3.4%, n = 629, P = 1.78 × 10–5). The Cancer Genome Atlas data further showed that ZNF750 genetic alterations were associated with early disease relapse. Previous ESCC studies have demonstrated that ZNF750 knockdown strongly promotes proliferation, migration, and invasion. Collectively, these results suggest a role for ZNF750 as a metastasis suppressor. TP53 is highly mutated in ESCC, and missense mutations are associated with poor overall survival, independently of pathological stage, suggesting that these missense mutations have important functional impacts on tumour progression, and are thus likely to be gain-of-function (GOF) mutations. Additionally, mutations of epigenetic regulators, including KMT2D, TET2, and KAT2A, and chromosomal 6p22 and 11q23 deletions of histone variants, which are important for nucleosome assembly, were detected in 80% of LN metastases. Our study highlights the important role of critical genetic events including ZNF750 mutations, TP53 putative GOF mutations and nucleosome disorganization caused by genetic lesions seen with ESCC metastasis.No Full Tex

Aberrant large tumor suppressor 2 (LATS2) gene expression correlates with EGFR mutation and survival in lung adenocarcinomas

BACKGROUND: Large tumor suppressor 2 (LATS2) gene is a putative tumor suppressor gene with potential roles in regulation of cell proliferation and apoptosis in lung cancer. The aim of this study is to explore the association of aberrant LATS2 expression with EGFR mutation and survival in lung adenocarcinoma (AD), and the effects of LATS2 silencing in both lung AD cell lines. METHODS: LATS2 mRNA and protein expression in resected lung AD were correlated with demographic characteristics, EGFR mutation and survival. LATS2-specific siRNA was transfected into four EGFR wild-type (WT) and three EGFR mutant AD cell lines and the changes in LATS2 expression and relevant signaling molecules before and after LATS2 knockdown were assayed. RESULTS: Fifty resected lung AD were included (M:F=23:27, smokers:non-smokers=19:31, EGFR mutant:wild-type=21:29) with LATS2 mRNA levels showed no significant difference between gender, age, smoking and pathological stages while LATS2 immunohistochemical staining on an independent set of 79 lung AD showed similar trend. LATS2 mRNA level was found to be a significant independent predictor for survival status (disease-free survival RR=0.217; p=0.003; Overall survival RR=0.238; p=0.036). siRNA-mediated suppression of LATS2 expression resulted in augmentation of ERK phosphorylation in EGFR wild-type AD cell lines with high basal LATS2 expression, discriminatory modulation of Akt signaling between EGFR wild-type and mutant cells, and induction of p53 accumulation in AD cell lines with low baseline p53 levels. CONCLUSIONS: LATS2 expression level is predictive of survival in patients with resected lung AD. LATS2 may modulate and contribute to tumor growth via different signaling pathways in EGFR mutant and wild-type tumors.postprin