Evaluation of an inactivated Ross River virus vaccine in active and passive mouse immunization models and establishment of a correlate of protection

Ross River Virus has caused reported outbreaks of epidemic polyarthritis, a chronic debilitating disease associated with significant long-term morbidity in Australia and the Pacific region since the 1920s. To address this public health concern, a formalin- and UV-inactivated whole virus vaccine grown in animal protein-free cell culture was developed and tested in preclinical studies to evaluate immunogenicity and efficacy in animal models. After active immunizations, the vaccine dose-dependently induced antibodies and protected adult mice from viremia and interferon α/β receptor knock-out (IFN-α/βR(-/-)) mice from death and disease. In passive transfer studies, administration of human vaccinee sera followed by RRV challenge protected adult mice from viremia and young mice from development of arthritic signs similar to human RRV-induced disease. Based on the good correlation between antibody titers in human sera and protection of animals, a correlate of protection was defined. This is of particular importance for the evaluation of the vaccine because of the comparatively low annual incidence of RRV disease, which renders a classical efficacy trial impractical. Antibody-dependent enhancement of infection, did not occur in mice even at low to undetectable concentrations of vaccine-induced antibodies. Also, RRV vaccine-induced antibodies were partially cross-protective against infection with a related alphavirus, Chikungunya virus, and did not enhance infection. Based on these findings, the inactivated RRV vaccine is expected to be efficacious and protect humans from RRV disease

Sound media musicianship

By the end of the 20th century the shift from professional recording studio to personal computer based recording systems was well established (Chadabe 1997) and musicians could increasingly see the benefits of value adding to the musical process by producing their own musical endeavours. At the Queensland University of Technology (QUT) where we were teaching, the need for a musicianship program that took account of these trends was becoming clear. The Sound Media Musicianship unit described in this chapter was developed to fill this need and ran from 1999 through 2010.

Self-regulation and mastery motivation in individuals with developmental disabilities : barriers, supports, and strategies

The development of the capacity for self-regulation represents an important achievement of childhood and is associated with social, behavioral, and academic competence (Bronson, 2001; Cleary & Zimmerman, 2004). Self-regulation evolves as individuals mature, with its final form integrating emotional, cognitive, and behavioral elements working together to achieve self-selected goals. This evolution is closely intertwined with the innate press to master the environment, labeled mastery motivation (Morgan, Harmon, & Maslin-Cole, 1990), as competence is the aim that underpins mastery motivation.

Physical performance profile of sub-elite juvenile Gaelic Games players and the prevalence of a Relative Age Effect (RAE)

Gaelic Games are the indigenous sports played in Ireland, the most popular being Gaelic football and hurling. The games are contact sports and the physical demands are thought to be similar to those of Australian Rules football, rugby union, rugby league, field hockey, and lacrosse (Delahunt et al., 2011). The difference in chronological age between children in a single age group is known as relative age and its consequences as the RAE, whereby younger players are disadvantaged (Del Campo et al., 2010). The purpose of this study was to describe the physical and performance profile of sub-elite juvenile Gaelic Games players and to establish if a RAE is present in this cohort and any influence physiological moderator variables may have on this. Following receipt of ethical approval (EHSREC11-45), six sub-elite county development squads (Under-14/15/16 age groups, male, n=115) volunteered to partake in the study. Anthropometric data including skin folds and girths were collected. A number of field tests of physical performance including 5 and 20m speed, vertical and broad jump distance, and an estimate of VO2max were carried out. Descriptive data are presented as Mean SD. Juvenile sub-elite Gaelic Games players aged 14.53 0.82 y were 172.87 7.63 cm tall, had a mass of 64.74 11.06 kg, a BMI of 21.57 2.82 kg.m-2 and 9.22 4.78 % body fat. Flexibility, measured by sit and reach was 33.62 6.86 cm and lower limb power measured by vertical and broad jump were 42.19 5.73 and 191.16 25.26 cm, respectively. Participant time to complete 5m, 20m and an agility test (T-Test) was 1.12 0.07, 3.31 0.30 and 9.31 0.55 s respectively. Participant’s estimated VO2max was 48.23 5.05 ml.kg.min-1. Chi-Square analysis of birth month by quartile (Q1 = January-March) revealed that a RAE was present in this cohort, whereby an over-representation of players born in Q1 compared with Q2, Q3 and Q4 was evident (2 = 14.078, df = 3, p = 0.003). Kruskal-Wallis analysis of the data revealed no significant difference in any of the performance parameters based on quartile of birth (Alpha level = 0.05).This study provides a physical performance profile of juvenile sub-elite Gaelic Games players, comparable with those of other sports such as soccer and rugby. This novel data can inform us of the physical requirements of the sport. The evidence of a RAE is similar to that observed in other contact sports such as soccer and rugby league (Carling et al, 2009; Till et al, 2010). Although a RAE exists in this cohort, this cannot be explained by any physical/physiological moderator variables. Carling C et al. (2009). Scandinavian Journal of Medicine and Science in Sport 19, 3-9. Delahunt E et al. (2011). Journal of Athletic Training 46, 241-5. Del Campo DG et al. (2010). Journal of Sport Science and Medicine 9, 190-198. Delorme N et al. (2010). European Journal of Sport Science 10, 91-96. Till K et al. (2010). Scandinavian Journal of Medicine and Science in Sports 20, 320-329.

A phase II study of mitomycin C and oral etoposide for advanced adenocarcinoma of the upper gastrointestinal tract

Background: Mitomycin C and etoposide have both demonstrated activity against gastric carcinoma. Etoposide is a topoisomerase II inhibitor with evidence for phase-specific and schedule-dependent activity. Patients and method. Twenty-eight consecutive patients with advanced upper gastrointestinal adenocarcinoma were treated with intravenous (i.v.) bolus mitomycin C 6 mg/m2 on day 1 every 21 days to a maximum of four courses. Oral etoposide capsules 50 mg b.i.d. (or 35 mg b.i.d. liquid) were administered days 1 to 10 extending to 14 days in subsequent courses if absolute neutrophil count >1.5 x 109/l on day 14 of first course, for up to six courses. Results: Twenty-six patients were assessed for response of whom 12 had measurable disease and 14 evaluable disease. Four patients had a documented response (one complete remission, three partial remissions) with an objective response rate of 15% (95% confidence interval (95% CI) 4%-35%). Eight patients had stable disease and 14 progressive disease. The median survival was six months. The schedule was well tolerated with no treatment-related deaths. Nine patients experienced leucopenia (seven grade II and two grade III). Nausea and vomiting (eight grade II, one grade III), fatigue (eight grade II, two grade III) and anaemia (seven grade II, two grade III) were the predominant toxicities. Conclusion: This out-patient schedule is well tolerated and shows modest activity in the treatment of advanced upper gastrointestinal adenocarcinoma. Further studies using protracted schedules of etoposide both orally and as infusional treatment should be developed.

Quality of life and survival in patients treated with radical chemoradiation alone for oesophageal cancer

Aims: To report cancer-specific and health-related quality-of-life outcomes in patients undergoing radical chemoradiation (CRT) alone for oesophageal cancer. Materials and methods: Between 1998 and 2005, 56 patients with oesophageal cancer received definitive radical CRT, due to local disease extent, poor general health, or patient choice. Data from European Organization for Research and Treatment of Cancer quality-of-life questionnaires QLQ-30 and QLQ-OES24 were collected prospectively. Questionnaires were completed at diagnosis, and at 3, 6 and 12 months after CRT where applicable. Results: The median follow-up was 18 months. The median overall survival was 14 months, with a 51, 26 and 13% 1-, 3- and 5-year survival, respectively. At 12 months after treatment there was a significant improvement compared with before treatment with respect to dysphagia and pain. Global health scores were not significantly affected. Conclusions: Considering the relatively short long-term survival for this cohort of patients, maximising the quality of those final months should be very carefully borne in mind from the outset. The health-related quality-of-life data reported herein helps to establish benchmarks for larger evaluation within randomised clinical trials. © 2007 The Royal College of Radiologists.

18FDG uptake during induction chemoradiation for oesophageal cancer fails to predict histomorphological tumour response

To determine whether [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) could predict the pathological response in oesophageal cancer after only the first week of neoadjuvant chemoradiation. Thirty-two patients with localised oesophageal cancer had a pretreatment PET scan and a repeat after the first week of chemoradiation. The change in mean maximum standardised uptake value (SUV) and volume of metabolically active tissue (MTV) was compared with the tumour regression grade (TRG) in the final histology. Those who achieved a TRG of 1 and 2 were deemed responders and 3-5 nonresponders. In the responders (28%), the SUV fell from 12.6 (±6.3) to 8.1 (±2.9) after 1 week of chemoradiation (P = 0.070). In nonresponders (72%), the results were 9.7 (±5.4) and 7.1 (±3.8), respectively (P = 0.003). The MTV in responders fell from 36.6 (±22.7) to 22.3 (±10.4) cm3 (P = 0.180), while in nonresponders, this fell from 35.9 (±36.7) to 31.9 (±52.7) cm3 (P = 0.405). There were no significant differences between responders and nonresponders. The hypothesis that early repeat FDG-PET scanning may predict histomorphologic response was not proven. This may reflect an inflammatory effect of radiation that obscures tumour-specific metabolic changes at this time. This assessment may have limited application in predicting response to multimodal regimens for oesophageal cancer. © 2006 Cancer Research UK.

Estimation of the burden of malignant neoplasms by DALYs in Shandong Province [应用伤残调整寿命年测量山东省恶性肿瘤疾病负担的研究]

Objective: To evaluate the burden of malignant neoplasms in Shandong Province in order to provide scientific evidence for policy-making. Methods: The main data for this study were from Shandong third cause of death sampling survey in 2006 and Shandong 2007 cancer prevalence survey. YLLs, YLDs, DALYs and disability weights of each type of cancers were calculated according to the global burdens of disease （GBD） methodology. The direct method was used to estimate YLDs. The uncertainty analysis was conducted following the methodology in GBD study. Results: The total cancers burden in Shandong population was 1 383 thousands DALYs. Lung cancer, liver cancer, stomach cancer and esophagus cancer were the top four cancers with the highest health burden. The burden of the four major cancers together accounted for 71.45% of the total burden of all cancers. 95% of the total burden of malignant tumors was caused by premature death, and only 5.26% of the total cancer burden was due to disability. The uncertainty of total burden estimate was around±11%， the uncertainty of YLDs was bigger than that of YLLs. Conclusion: The health burden due to cancers in Shandong population is heavier than that of the national average level. Liver cancer, lung cancer and stomach cancer should be the major cancers for disease control and prevention in Shandong.

Gene expression analysis of diagnostic biopsies predicts pathological response to neoadjuvant chemoradiotherapy of esophageal cancer

OBJECTIVE: This study explored gene expression differences in predicting response to chemoradiotherapy in esophageal cancer. PURPOSE:: A major pathological response to neoadjuvant chemoradiation is observed in about 40% of esophageal cancer patients and is associated with favorable outcomes. However, patients with tumors of similar histology, differentiation, and stage can have vastly different responses to the same neoadjuvant therapy. This dichotomy may be due to differences in the molecular genetic environment of the tumor cells. BACKGROUND DATA: Diagnostic biopsies were obtained from a training cohort of esophageal cancer patients (13), and extracted RNA was hybridized to genome expression microarrays. The resulting gene expression data was verified by qRT-PCR. In a larger, independent validation cohort (27), we examined differential gene expression by qRT-PCR. The ability of differentially-regulated genes to predict response to therapy was assessed in a multivariate leave-one-out cross-validation model. RESULTS: Although 411 genes were differentially expressed between normal and tumor tissue, only 103 genes were altered between responder and non-responder tumor; and 67 genes differentially expressed >2-fold. These included genes previously reported in esophageal cancer and a number of novel genes. In the validation cohort, 8 of 12 selected genes were significantly different between the response groups. In the predictive model, 5 of 8 genes could predict response to therapy with 95% accuracy in a subset (74%) of patients. CONCLUSIONS: This study has identified a gene microarray pattern and a set of genes associated with response to neoadjuvant chemoradiation in esophageal cancer. The potential of these genes as biomarkers of response to treatment warrants further investigation. Copyright © 2009 by Lippincott Williams & Wilkins.

Evolving progress in oncologic and operative outcomes for esophageal and junctional cancer : lessons from the experience of a high-volume center

Objective: Modern series from high-volume esophageal centers report an approximate 40% 5-year survival in patients treated with curative intent and postoperative mortality rates of less than 4%. An objective analysis of factors that underpin current benchmarks within high-volume centers has not been performed. Methods: Three time periods were studied, 1990 to 1998 (period 1), 1999 to 2003 (period 2), and 2004 to 2008 (period 3), in which 471, 254, and 342 patients, respectively, with esophageal cancer were treated with curative intent. All data were prospectively recorded, and staging, pathology, treatment, operative, and oncologic outcomes were compared. Results: Five-year disease-specific survival was 28%, 35%, and 44%, and in-hospital postoperative mortality was 6.7%, 4.4%, and 1.7% for periods 1 to 3, respectively (P < .001). Period 3, compared with periods 1 and 2, respectively, was associated with significantly (P < .001) more early tumors (17% vs 4% and 6%), higher nodal yields (median 22 vs 11 and 18), and a higher R0 rate in surgically treated patients (81% vs 73% and 75%). The use of multimodal therapy increased (P < .05) across time periods. By multivariate analysis, age, T stage, N stage, vascular invasion, R status, and time period were significantly (P < .0001) associated with outcome. Conclusions: Improved survival with localized esophageal cancer in the modern era may reflect an increase of early tumors and optimized staging. Important surgical and pathologic standards, including a higher R0 resection rate and nodal yields, and lower postoperative mortality, were also observed. Copyright © 2012 by The American Association for Thoracic Surgery.

Long-term outcomes following neoadjuvant chemoradiotherapy for esophageal cancer

OBJECTIVE: We present and analyze long-term outcomes following multimodal therapy for esophageal cancer, in particular the relative impact of histomorphologic tumor regression and nodal status. PATIENTS AND METHODS: A total of 243 patients [(adenocarcinoma (n = 170) and squamous cell carcinoma (n = 73)] treated with neoadjuvant chemoradiotherapy in the period 1990 to 2004 were followed prospectively with a median follow-up of 60 months. Pathologic stage and tumor regression grade (TRG) were documented, the site of first failure was recorded, and Kaplan-Meier survival curves were plotted. RESULTS: Thirty patients (12%) did not undergo surgery due to disease progression or deteriorated performance status. Forty-one patients (19%) had a complete pathologic response (pCR), and there were 31(15%) stage I, 69 (32%) stage II, and 72 (34%) stage III cases. The overall median survival was 18 months, and the 5-year survival was 27%. The 5-year survival of patients achieving a pCR was 50% compared with 37% in non-pCR patients who were node-negative (P = 0.86). Histomorphologic tumor regression was not associated with pre-CRT cTN stage but was significantly (P < 0.05) associated with ypN stage. By multivariate analysis, ypN status (P = 0.002) was more predictive of overall survival than TRG (P = 0.06) or ypT stage (P = 0.39). CONCLUSION: Achieving a node-negative status is the major determinant of outcome following neoadjuvant chemoradiotherapy. Histomorphologic tumor regression is less predictive of outcome than pathologic nodal status (ypN), and the need to include a primary site regression score in a new staging classification is unclear. © 2007 Lippincott Williams & Wilkins, Inc.

Differential pathologic variables and outcomes across the spectrum of adenocarcinoma of the esophagogastric junction

Background Adenocarcinoma of the esophagogastric junction (AEG) as described by Siewert et al. is classified as one entity in the latest (7th Edition) American Joint Cancer Committee/International Union Against Cancer (AJCC/UICC) manual, compared with the previous mix of esophageal and gastric staging systems. The origin of AEG tumors, esophageal or gastric, and their biology remain controversial, particularly for AEG type II (cardia) tumors. Methods We adapted a large prospective database (n = 520: 180 type I, 182 type II, 158 type III) to compare AEG tumors under the new TNM system Pathological variables associated with prognosis were compared (pT, pN, stage, differentiation, R status, lymphovascular invasion, perineural involvement, number of positive nodes, percent of positive nodes, and tumor length), as well as overall survival. Results Compared with AEG type I tumors, type II and type III tumors had significantly (p\0.05) more advanced pN stages, greater number and percentage of positive nodes, poorer differentiation, more radial margin involvement, and more perineural invasion. In AEG type I, 14/180 patients (8%) had[6 involved nodes (pN3), compared with 16 and 30% of patients classified type II and III, respectively. Median survival was significantly (p = 0.03) improved for type I patients (38 months) compared with those with tumors classified as type II (28 months) and type III (24 months). In multivariate analysis node positivity and pN staging but not AEG site had an impact on survival. Conclusions In this series AEG type I is associated with more favorable pathologic features and improved outcomes compared with AEG type II and III. This may reflect earlier diagnosis, but an alternative possibility, that type I may be a unique paradigm with more favorable biology, requires further study. © Société Internationale de Chirurgie 2010.