Sex- and age-dependent association of SLC11A1 polymorphisms with tuberculosis in Chinese: a case control study

BACKGROUND: Host genetic factors are important determinants in tuberculosis (TB). The SLC11A1 (or NRAMP1) gene has been studied extensively for genetic association with TB, but with inconsistent findings. In addition, no study has yet looked into the effect of sex and age on the relationship between SLC11A1 polymorphisms and TB. METHODS: A case-control study was conducted. In total, 278 pulmonary TB patients and 282 sex- and age-matched controls without TB were recruited. All subjects were ethnic Chinese. On the basis of linkage disequilibrium pattern, three genetic markers from SLC11A1 and one from the nearby IL8RB locus were selected and examined for association with TB susceptibility. These markers were genotyped using single strand conformation polymorphism analysis or fragment analysis of amplified products. RESULTS: Statistically significant differences in allele (P = 0.0165, OR = 1.51) and genotype (P = 0.0163, OR = 1.59) frequencies of the linked markers SLC6a/b (classically called D543N and 3'UTR) of the SLC11A1 locus were found between patients and controls. With stratification by sex, positive associations were identified in the female group for both allele (P = 0.0049, OR = 2.54) and genotype (P = 0.0075, OR = 2.74) frequencies. With stratification by age, positive associations were demonstrated in the young age group (age ≤65 years) for both allele (P = 0.0047, OR = 2.52) and genotype (P = 0.0031, OR = 2.92) frequencies. All positive findings remained significant even after correction for multiple comparisons. No significant differences were noted in either the male group or the older age group. No significant differences were found for the other markers (one SLC11A1 marker and one IL8RB marker) either. CONCLUSION: This study confirmed the association between SLC11A1 and TB susceptibility and demonstrated for the first time that the association was restricted to females and the young age group

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Some aspects of fluvial erosion in three small catchments, New Territories, Hong Kong

published_or_final_versionGeography and GeologyMasterMaster of Philosoph

The effects of information bias and riding frequency on noise annoyance to a new railway extension in Hong Kong

We investigate how two non-acoustic factors, information bias and riding frequency, can affect the annoyance response of an urban population to noise created by a new railway line. The study shows that information bias is asymmetrical. Respondents receiving only information on positive measures taken by the authority to reduce noise emission are more tolerant of the noise impact, but those receiving only critical views tend to be more annoyed because they feel that not all measures to reduce noise have been employed. Additionally people who use the line frequently are more tolerant to the noise impact than those who do not. Information bias seems to have a temporary masking effect over riding frequency lasting for a few weeks after railway opening. This suggest that whilst free flow of information provided by the authority can help alleviate annoyance response, encouraging the people affected to make use of the new infrastructure may be useful to reduce public resistance and noise annoyance

Facility siting in the Asia-Pacific: perspectives on knowledge production and application

This volume explores the management of conflicts arising from the siting of unwanted projects in the Asia-Pacific, a region inadequately explored by the relevant literature. The work includes studies on a variety of locations, including Hong Kong, Japan, Mainland China, Taiwan, Vietnam, Singapore, and others. Contributions are drawn from several leading scholars intimately familiar with the locations under study, and employ theoretical, comparative, and policy-based approaches to analysis of environmental conflict, risk management, and public participation. The editors also provide introductory and concluding sections in which the siting issues under discussion are summarized and contextualized. The result is a collection that serves as an invaluable aid and source of information for policymakers, environmentalists, and scholars of the Asia-Pacific and elsewhere

STRATEGIC ENVIRONMENTAL ASSESSMENT IN CHINA: OPPORTUNITIES, ISSUES AND CHALLENGES

Based on literature reviews, case studies and other information available on the web, this paper examines the evolution and status of strategic environmental assessment in China by reviewing the progress that has been made; discussing the issues and problems encountered and exploring the best way forward. It is suggested that the Chinese EIA system has evolved over the years to cope with the rapidity and scale of development in China and the current emphasis on Plan EIA is probably the most appropriate form of SEA given the political reality and complicated institution setup. Given China's environmental and resource problems, the paper affirms the potential role of SEA in fostering a sustainable and harmonious society and the need to mainstream sustainability considerations in the formulation of national plans and strategies. To circumvent political resistance from line agencies, the paper suggests that SEA can be applied, in various names and forms, to national and provincial socio-economic plans.Strategic environmental assessment, stakeholder analysis, national socio-economic plan

Partial and Total Annoyance Due to Road Traffic Noise Combined with Aircraft or Railway Noise: Structural Equation Analysis

International audienc