Cancer vaccines: uses of HLA transgenic mice compared to genetically modified mice

Many tumor antigens have been identified that can be targeted by the immune system. Animal models that have been genetically modified to express human HLA molecules instead of their own MHC antigens have shown to be valuable in the discovery of peptides derived from tumor antigens many of which have since been used in clinical trials with varying degrees of success. Although these models are not perfect, they nonetheless allow transplantable tumor models to be developed to evaluate novel vaccination strategies that can then be applied in humans. In addition animals that have been genetically modified to “spontaneously” generate tumors that will grow within their correct environment are of greater value for studying angiogenesis, metastasis and the relationship between the immune system and tumor in a physiological setting. In this review, mice genetically modified to express HLA genes or to spontaneously develop tumors are discussed, highlighting their advantages and limitations as preclinical models for cancer immunotherapy

A Private Sector Perspective on the Celtic Tiger Experience

International Relations/Trade,

Player violence or violent players? Vicarious liability for sports participants

This article analyses two recent English cases concerning the law on vicarious liability for acts of violence and considers their significance in respect of on-field acts of violence in contact sports. It provides an overview of how the law of negligence has developed in the specific context of sports injuries (including the application of the defence of volenti) and critiques the application of vicarious liability to sports cases. This is followed by a consideration of the wider law on vicarious liability for violent employees through a review of Lister v Hesley Hall Ltd [2001] UKHL 22 and a deeper consideration of Mattis v Pollock [2003] EWCA Civ 887. The article continues with an analysis of how those decisions have changed the legal landscape in respect of violent sports participants, looking in particular at reported cases from three jurisdictions in which that issue has been raised

The convertible engine: A dual-mode propulsion system

A variable inlet guide vane (VIGV) convertible engine that could be used to power future high-speed rotorcraft was tested on an outdoor stand. The engine ran stably and smoothly in the turbofan, turboshaft, and dual (combined fan and shaft) power modes. In the turbofan mode with the VIGV open, fuel consumption was comparable to that of a conventional turbofan engine. In the turboshaft mode with the VIGV closed, fuel consumption was higher than that of present turboshaft engines because power was wasted in churning fan-tip air flow. In dynamic performance tests with a specially built digital engine control and using a waterbrake dynamometer for shaft load, the engine responded effectively to large steps in thrust command and shaft torque. Previous mission analyses of a conceptual X-wing rotorcraft capable of 400-knot cruise speed were revised to account for more fan-tip churning power loss that was originally estimated. The calculations confirm that using convertible engines rather than separate life and cruise engines would result in a smaller, lighter craft with lower fuel use and direct operating cost

Outdoor test stand performance of a convertible engine with variable inlet guide vanes for advanced rotorcraft propulsion

A variable inlet guide van (VIGV) type convertible engine that could be used to power future high-speed rotorcraft was tested on an outdoor stand. The engine ran stably and smoothly in the turbofan, turboshaft, and dual (combined fan and shaft) power modes. In the turbofan mode with the VIGV open fuel consumption was comparable to that of a conventional turbofan engine. In the turboshaft mode with the VIGV closed fuel consumption was higher than that of present turboshaft engines because power was wasted in churning fan-tip airflow. In dynamic performance tests with a specially built digital engine control and using a waterbrake dynamometer for shaft load, the engine responded effectively to large steps in thrust command and shaft torque. Previous mission analyses of a conceptual X-wing rotorcraft capable of 400-knot cruise speed were revised to account for more fan-tip churning power loss than was originally estimated. The new calculations confirm that using convertible engines rather than separate lift and cruise engines would result in a smaller, lighter craft with lower fuel use and direct operating cost

Test stand performance of a convertible engine for advanced V/STOL and rotorcraft propulsion

A variable inlet guide vane (VIGV) convertible engine that could be used to power future high-speed V/STOL and rotorcraft was tested on an outdoor stand. The engine ran stably and smoothly in the turbofan, turboshaft, and dual (combined fan and shaft) power modes. In the turbofan mode with the VIGV open, fuel consumption was comparable to that of a conventional turbofan engine. In the turboshaft mode with the VIGV closed, fuel consumption was higher than that of present turboshaft engines because power was wasted in churning fan-tip air flow. In dynamic performance tests with a specially built digital engine control and using a waterbrake dynamometer for shaft load, the engine responded effectively to large steps in thrust command and shaft torque

The impact of old age on cancer-specific and non-cancer-related survival following elective potentially curative surgery for Dukes A/B colorectal cancer

Previous studies have suggested that survival following surgery for colorectal cancer is poorer in the elderly. However, the findings were inconsistent and none of the studies adjusted for case mix. The aim of this study was to establish whether there were age-related differences in cancer (colorectal)-specific and non-cancer (colorectal)-related survival in patients undergoing elective potentially curative resection for Dukes stage A/B colorectal cancer. One thousand and forty three patients who underwent elective potentially curative resection for Dukes' A/B colorectal cancer between 1991 and 1994 in 11 hospitals in Scotland were included in the study. Ten year cancer-specific and non-cancer-related survival and the hazard ratios were calculated according to age groups (<64; 65–74/>74 years). On follow-up 273 patients died of their cancer and 328 died of non-cancer-related causes. At 10 years, overall survival was 45%, cancer specific was 70% and non-cancer-related survival was 64%. On multivariate analysis of all factors, age (HR 1.38, 95% CI 1.18–1.62, P<0.001), sex (HR 1.74, 95% CI 1.36–2.23, P<0.001), site (HR 1.42, 95% CI 1.11–1.81, P<0.01) and Dukes' stage (HR 1.71, 1.19–2.47, P<0.01) were independently associated with cancer-specific survival. On multivariate analysis of all factors, age (HR 2.14, 1.84–2.49, P<0.001), sex (HR 1.43, 1.15–1.79, P<0.01) and deprivation (HR 1.30, 1.09–1.55, P<0.01) were independently associated with non-cancer-related survival. The results of this study show that increasing age impacts negatively both on cancer-specific and non-cancer-related survival following elective potentially curative resection for node-negative colorectal cancer. However, the effect of increasing age is greater on the non-cancer-related survival. These results suggest that cancer-specific and non-cancer-related mortality should be considered separately in survival analysis of these cancer patients

A clinical risk score to predict 3-, 5- and 10-year survival in patients undergoing surgery for Dukes B colorectal cancer

<p>Background: The prognosis of patients with Dukes stage B colorectal cancer is unpredictable and there is continuing interest in simply and reliably identifying patients at high risk of developing recurrence and dying of their disease. The aim of this study was to devise a clinical risk score to predict 3-, 5- and 10-year survival in patients undergoing surgery for Dukes stage B colorectal cancer.</p> <p>Methods: A total of 1350 patients who underwent surgery for Dukes stage B colorectal cancer between 1991 and 1994 in 11 hospitals in Scotland were included in the analysis.</p> <p>Results: On follow-up, 926 patients died of whom 479 died of their cancer. At 10 years, cancer-specific survival was 61% and overall survival was 38%. On multivariate analysis, age ≥75 (hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.15-1.82, P=0.001), emergency presentation (HR 1.59, 95% CI 1.27-1.99, P<0.001) and anastomotic leak (HR 2.17, 95% CI 1.24-3.78, P<0.01) were independently associated with cancer-specific survival in colon cancer. On multivariate analysis, only age ≥75 (HR 1.58, 95% CI 1.14-2.18, P<0.01) was associated with cancer-specific survival in rectal cancer. Age, presentation and anastomotic leak hazards could be simply added to form a clinical risk score from 0 to 2 in colon cancer. In patients with Dukes B stage colon cancer, the cancer-specific survival at 5 years for patients with a cumulative score 0 was 81%, 1 was 67% and 2 was 63%. The cancer-specific survival rate at 10 years for patients with a clinical risk score of 0 was 72%, 1 was 58% and 2 was 53%.</p> <p>Conclusion: The results of this study, in a mature cohort, introduce a new simple clinical risk score for patients undergoing surgery for Dukes B colon cancer. This provides a solid foundation for the examination of the impact of additional factors and treatment on prediction of 3-, 5- and 10-year cancer-specific survival.</p&gt