Improve Space and Manpower Utilisation

See also the data for the project http://ink.library.smu.edu.sg/researchdata/17/</p

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

Making sense of coworker friendships : choice, constraint, and (imagined) boundaries.

Workplace friendships are commonly assumed to be voluntarily chosen ties. But are these relationships purely a matter of personal choice? This study has three main concerns: it seeks to understand the different ways by which individuals negotiate and make sense of friendships with peer coworkers; it examines how freedom of choice in friendship may be circumscribed by social arrangements over which one has limited control; and it questions taken-for-granted distinctions between spheres of personal-life and work-life. Through semi-structured in-depth interviews, findings suggest that 1) besides personal choice, the development of workplace friendship is also shaped by the social organization of the workplace over which one has limited control; 2) the patterning of friendships represents a measure of individual agency within one’s socially governed friendship experience; and 3) boundaries separating work-life and personal-life are often blurred in the doing of workplace friendships. This study may add to existing workplace friendship literature, with a qualitative focus on individuals’ subjective meanings.Bachelor of Art

Influence of anterior vaginal mesh with concomitant mid-urethral sling surgery on stress urinary incontinence: Clinical and sonographic outcome

Introduction To clinically and sonographically evaluate the influence of anterior vaginal mesh (AVM) surgery with concomitant mid-urethral sling surgery (MUS) for stress urinary incontinence (SUI). Materials and Methods Women with severe symptomatic pelvic organ prolapse (POP) stage III or IV with concomitant SUI were divided into two groups: Group I had transobturator tape (TOT) and AVM surgery and Group II underwent TOT without AVM surgery. Clinical outcome was assessed pre-operatively and 1 year post-operatively, while ultrasound evaluations were performed after one year. Objective cure was defined as no urinary leakage demonstrable on provocative filling cystometry. Subjective SUI cure was a negative response to Urogenital Distress Inventory Six (UDI-6) (question 3). Results A total of 97 women were recruited, 57 in Group I and 40 in Group II. Three women had symptomatic prolapse in Group I and 5 in Group II. There were no differences in the ultrasound and clinical outcomes between women who had mid-urethral slings with and without AVM. Successful SUI outcome was reported in 85 women. Urethral kinking was demonstrable in 50% of successful cases, but none with failed outcomes. Subanalysis among those with successful SUI outcome (n = 85) and failure (n = 12) revealed the tape, bladder neck and mesh mobility was significantly higher (P \u3c 0.001) among those with SUI success. Conclusions Among women who had MUS, there were no differences in the ultrasound and clinical outcome between those who had AVM or otherwise

Comparison between Elevate Anterior/Apical system and Perigee system in pelvic organ prolapse surgery: clinical and sonographic outcomes

Objective: The aim of this study was to assess the incidence of de novo stress urinary incontinence (SUI) and sonographic features of implanted transvaginal mesh in continent women treated with Elevate™ anterior/apical [single-incision mesh (SIM-A)] or Perigee™ [transvaginal mesh with sacrospinous fixation (TVM + SSF)] in extensive pelvic organ reconstruction surgery. Methods: This prospective observational study was done from May 2010 to January 2013. Patients were recruited from two tertiary centers, and the Elevate™ and Perigee™ systems were compared. Patients who had overt or occult SUI, previous prolapse or mesh insertion were excluded. Result: Fifty-seven patients in the SIM-A group and sixty-one in the TVM + SSF group were analysed. All completed a minimum of 1-year follow-up. Groups were demographically and statistically similar. There was a significantly high incidence of de novo SUI postoperatively in the SIM-A group. The objective and subjective cure rate of pelvic organ prolapse (POP) were comparable between groups, with incidence of mesh erosion in the SIM-A group and three in the TVM + SSF group. Sonographic evaluation showed significant increase in mesh length in the SIM-A group. Conclusion: Elevate™ a offered lower incidence of mesh erosion and comparable results on anatomical POP correction; however, incidence of de novo SUI was high. There is an apparent lengthening of implanted Elevate® mesh sonographically

Association of urodynamics and lower urogenital tract nerve growth factor after synthetic vaginal mesh implantation on a rat model

Aim: By investigating the association of urodynamics and urogenital nerve growth factor (NGF) levels in vaginal mesh surgery, we may be able to associate the likelihood of postoperative lower urinary tract symptoms developing as a result of synthetic mesh implanted for pelvic floor reconstructive surgery. Methods: Thirty-eight female Sprague–Dawley rats were divided into three groups: mesh, sham (no mesh), and control. Urodynamic study and NGF analysis of the urogenital tissues were done and results were compared among all groups. The urodynamic studies of the mesh and sham groups were further divided into the 4th and 10th days. A P-value \u3c 0.05 was considered statistically significant. Results: All rats survived and no complications were observed during the post-implantation period. Histological evaluation showed intense acute inflammatory reaction on days 4 and 7 in the mesh and sham groups when compared to the control. The mesh group showed a larger area of inflammation as compared to the sham. The NGF levels increased significantly in the mesh and sham groups on the 4th and 10th days when compared to the control (P \u3c 0.001, P \u3c 0.001, respectively). Both the mesh and sham groups had shorter voiding interval and lower voiding volume on days 4 and 10 when compared to the control group (P \u3c 0.001, P \u3c 0.001, respectively). The magnitude on increasing NGF level and decreasing voiding interval and voiding volume was significantly more on the mesh group than the sham group. Conclusion: A higher level of NGF in the early days post-transvaginal mesh implantation is associated with a shorter voiding interval and a smaller bladder capacity, which represents abnormal lower urinary tract symptoms following transvaginal mesh implantation

Genome-wide Association Study Identifies Five New Susceptibility Loci For Primary Angle Closure Glaucoma

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 x 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 x 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 x 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 x 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 x 10(-12)). We also confirmed significant association at three previously described loci (P < 5 x 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18)(1), providing new insights into the biology of PACG.485556+Singapore Ministry of Health's National Medical Research Council under its Translational and Clinical Research (TCR) Flagship Programme Grant Stratified Medicine for Primary Angle Closure Glaucoma [NMRC/TCR/008-SERI/2013]Singapore Translational Research (STaR) Investigator Award Singapore Angle Closure Glaucoma Program Characterization, Prevention, and Management [NMRC/STAR/0023/2014]Biomedical Research CouncilAgency for Science, Technology and Research (A-STAR), SingaporeUniversiti Sains Malaysia [RUI 1001/PPSP/812101, RUI 1001/PPSP/812152]Program of Beijing ScholarsLeading Talents-High-Level Talents of the Health System of Beijing [2009-1-05]National Major Scientific and Technological Special Project for 'Significant New Drugs Development' [2011ZX09302-007-05]National Natural Science Foundation of China [81570837

Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma.

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG