The Effects of X-irradiation and Anti-lymphocyte Serum on the Responses to Tumour Allografts

The growth of a CBA mammary adenocarcinoma has been studied following transplantation to syngeneic and allogeneic recipients, with particular reference to the susceptibilities of the primary and secondary responses elicited by the tumour allografts, to impairment by whole-body X-irradiation and by treatment with rabbit-anti-mouse lymphocyte serum. In syngeneic recipients, the diameter of tumour implants increases linearly with time and there is no difference in the growth curves in females and in males. Later tumour generations grow faster than earlier generations. In allogeneic recipients, there is a relationship between the tumour diameter on day 21 (T) and the dose of X-irradiation (D) administered before implantation

A role for topoisomerase IIα in the formation of radiation-induced chromatid breaks

Chromatid breaks in cells exposed to low dose irradiation are thought to be initiated by DNA double-strand breaks (DSB), and the frequency of chromatid breaks has been shown to increase in DSB rejoining deficient cells. However, the underlying causes of the wide variation in frequencies of G2 chromatid breaks (or chromatid ‘radiosensitivity') in irradiated T-lymphocytes from different normal individuals and cancer cases are as yet unclear. Here we report evidence that topoisomerase IIα expression level is a factor determining chromatid radiosensitivity. We have exposed the promyelocytic leukaemic cell line (HL60) and two derived variant cell lines (MX1 and MX2) that have acquired resistance to mitoxantrone and low expression of topoisomerase II α, to low doses of γ-radiation and scored the induced chromatid breaks. Chromatid break frequencies were found to be significantly lower in the variant cell lines, compared with their parental HL60 cell line. Rejoining of DSB in the variant cell lines was similar to that in the parental HL60 strain. Our results indicate the indirect involvement of topoisomerase IIα in the formation of radiation-induced chromatid breaks from DSB, and suggest topoisomerase IIα as a possible factor in the inter-individual variation in chromatid radiosensitivity

A value-based approach to optimizing long-term maintenance plans for a multi-asset k-out-of-N system

Devising a long-term maintenance plan for a system of large infrastructure assets is an exacting task. Any maintenance activity that induces system downtime can incur a massive production or service loss. This problem becomes increasingly challenging for a system of which the performance is based on the collective output of assets. Current approaches that optimise each asset in isolation or consider a binary performance relationship insufficiently address this issue because the negligence of performance interactions among assets results in an inaccurate cost estimation. To overcome these hurdles, we formulate a mathematical model that explicitly demonstrates dynamic risk of production loss according to the system aggregate output. Further, we propose an integrated solution method that couples a finite loop search with a Genetic Algorithm. Application of our model to a real-world case study has proved to simultaneously strike the balance between cost and risk. Validated by Monte Carlo simulation, the proposed model has shown to outperform existing approaches. By systematically scheduling maintenance actions over the planning horizon, the resultant strategy has demonstrated to offer considerable maintenance cost savings and significantly prolong the average asset life. Sensitivity analyses also evince the robustness of the proposed model under the volatility in key parameters.EPSRC (This does not appear on the submitted manuscript yet, but will be added in the final proof

Chromosomal radiosensitivity in G2-phase lymphocytes identifies breast cancer patients with distinctive tumour characteristics

A substantial proportion of women with breast cancer exhibit an abnormally high radiosensitivity as measured by the frequency of chromatid breaks induced in G2-phase, PHA stimulated lymphocytes. Chromatid break frequencies were compared for a cohort of previously untreated sporadic breast cancer patients and hospital outpatient controls. In the breast cancer group 46% showed high radiosensitivity compared to 14% of controls (P< 0.001). Comparison of those breast cancer patients with a high G2radiosensitivity (G2RS) versus those with a low G2RS showed no difference in menopausal status or age but the high G2RS group had on average a lower score on the Nottingham Prognostic Index. Predicted survival in the high G2RS group at 15 years was 55% compared to 36% for the low G2RS group. Furthermore, 81% of tumours from the high G2RS were oestrogen receptor positive compared to 45% from the low G2RS group. Thus high G2RS identifies a sub-population of patients with distinctive tumour characteristics and with a predicted improved prognosis as compared with those in the low G2RS group. Our findings imply that besides influencing risk of breast cancer the genetic factors determining G2radiosensitivity also influence the tumour characteristics and prognosis in these patients. © 2001 Cancer Research Campaign  http://www.bjcancer.co

Identification of Movement Strategies during the Sit-to-Walk Movement in Patients with Knee Osteoarthritis

Patients with osteoarthritis (OA) of the knee commonly alter their movement to compensate for deficiencies. This study presents a new numerical procedure for classifying sit-to-walk (STW) movement strategies. Ten control and twelve OA participants performed the STW task in a motion capture laboratory. A full body biomechanical model was used. Participants were instructed to sit in a comfortable self-selected position on a stool height adjusted to 100% of their knee height and then stand and pick up an object from a table in front of them. Three matrices were constructed defining the progression of the torso, feet and hands in the sagittal plane along with a fourth expressing the location of the hands relative to the knees. Hierarchical clustering (HC) was used to identify different strategies. Trials were also classified as to whether the left (L) and right (R) extremities used a matching strategy (bilateral) or not (asymmetrical). Fisher’s exact test was used to compare this between groups. Clustering of the torso matrix dichotomised the trials in two major clusters; subjects leaning forward (LF) or not. The feet and hands matrices revealed sliding the foot backward (FB) and moving an arm forward (AF) strategies respectively. Trials not belonging in the AF cluster were submitted to the last HC of the fourth matrix exposing three additional strategies, the arm pushing through chair (PC), arm pushing through knee (PK) and arm not used (NA). The control participants used the LF+FBR+PK combination most frequently whereas the OA participants used the AFR+PCL. OA patients used significantly more asymmetrical arm strategies, p=0.034. The results demonstrated that control and OA participants favour different STW strategies. The OA patients asymmetrical arm behaviour possibly indicates compensating for weakness of the affected leg. These strategy definitions may be useful to assess post-operative outcomes and rehabilitation progress