Recognition of O6MeG lesions by MGMT and mismatch repair proficiency may be a prerequisite for low-dose radiation hypersensitivity

Low-dose hyper-radiosensitivity (HRS) is the phenomenon whereby cells exposed to radiation doses of less than approximately 0.5 Gy exhibit increased cell killing relative to that predicted from back-extrapolating high-dose survival data using a linear-quadratic model. While the exact mechanism remains to be elucidated, the involvement of several molecular repair pathways has been documented. These processes in turn are also associated with the response of cells to O6-methylguanine (O6MeG) lesions. We propose a model in which the level of low-dose cell killing is determined by the efficiency of both pre-replicative repair by the DNA repair enzyme O6-methylguanine methyltransferase (MGMT) and post-replicative repair by the DNA mismatch repair (MMR) system. We therefore hypothesized that the response of cells to low doses of radiation is dependent on the expression status of MGMT and MMR proteins. MMR (MSH2, MSH6, MLH1, PMS1, PMS2) and MGMT protein expression signatures were determined in a panel of normal (PWR1E, RWPE1) and malignant (22RV1, DU145, PC3) prostate cell lines and correlated with clonogenic survival and cell cycle analysis. PC3 and RWPE1 cells (HRS positive) were associated with MGMT and MMR proficiency, whereas HRS negative cell lines lacked expression of at least one (MGMT or MMR) protein. MGMT inactivation had no significant effect on cell survival. These results indicate a possible role for MMR-dependent processing of damage produced by low doses of radiation.

Birth technology competence: a concept analysis

Aim. To identify birth technology competencies used by midwives to support women during the birthing process and to explore the concept of birth technology competence in midwifery practice in order to inform both education and practice. Objective. To define attributes of birth technology competence. Method. The Chinn and Kramer framework for concept analysis was used to examine sources including popular and professional literature, government reports and statutory regulation. The model allows for the exploration of three areas of experience, which interact to form the meaning of an idea or concept – feelings, values and attitudes associated with the concept, the symbolic label for the concept and the concept itself. Results. Exploration of the literature led to the development of exemplar cases that illuminate tentative attributes of the concept, contained within three domains – interpersonal skills, professional knowledge and clinical proficiency. Implications. Following testing in midwifery practice to ensure its transferability into the clinical context, the theoretical perspective developed here will provide a basis to inform education and practice in relation to the use of technology.

Ethnography of technological competence in clinical midwifery practice

Background. Concept analysis has identified three domains in the competent use of birth technology â?? interpersonal skills, professional knowledge and clinical proficiency â?? and tentative criteria for birth technology competence. Aim. Fieldwork was undertaken to observe, confirm and explore pre-defined attributes of birth technology competence. Method. The Swartz-Barcott and Kim (2000) hybrid model of concept development was expanded to include an ethnographic observation of theory in action. Findings. Key attributes of birth technology competence found in â??real-worldâ?? midwifery practice were skills in using the machines, decision-making and traditional midwifery skills. Conclusions. The confusion surrounding the use of technology in midwifery practice needs to be addressed by both professionals and educationalists. Midwives should be taught to value traditional midwifery skills alongside those of machine skills. The identification of a model of appropriate technology use is needed in midwifery.

Prosodic Characteristics of Skilled Reading: Fluency and Expressiveness in 8- 10-year-old Readers

Statistical methods of describing prosody were used to study fluency, expressiveness and their relationship among 8-10-year-old readers. There were robust relationships between expressiveness and variables associated with pitch mobility; and between fluency and measures associated with temporal organization. Interactions indicated that the relationships were not simple. Differences between groups depended on sentence content and position. Some measures offer a basis for rules aimed at assigning individuals to skill categories. The effects suggest psychological hypotheses about the underlying mechanisms.