Theoretical analysis of the dose dependence of the oxygen enhancement ratio and its relevance for clinical applications

<p>Abstract</p> <p>Background</p> <p>The increased resistance of hypoxic cells to ionizing radiation is usually believed to be the primary reason for treatment failure in tumors with oxygen-deficient areas. This oxygen effect can be expressed quantitatively by the oxygen enhancement ratio (OER). Here we investigate theoretically the dependence of the OER on the applied local dose for different types of ionizing irradiation and discuss its importance for clinical applications in radiotherapy for two scenarios: small dose variations during hypoxia-based dose painting and larger dose changes introduced by altered fractionation schemes.</p> <p>Methods</p> <p>Using the widespread Alper-Howard-Flanders and standard linear-quadratic (LQ) models, OER calculations are performed for T1 human kidney and V79 Chinese hamster cells for various dose levels and various hypoxic oxygen partial pressures (pO2) between 0.01 and 20 mmHg as present in clinical situations <it>in vivo</it>. Our work comprises the analysis for both low linear energy transfer (LET) treatment with photons or protons and high-LET treatment with heavy ions. A detailed analysis of experimental data from the literature with respect to the dose dependence of the oxygen effect is performed, revealing controversial opinions whether the OER increases, decreases or stays constant with dose.</p> <p>Results</p> <p>The behavior of the OER with dose per fraction depends primarily on the ratios of the LQ parameters alpha and beta under hypoxic and aerobic conditions, which themselves depend on LET, pO2 and the cell or tissue type. According to our calculations, the OER variations with dose <it>in vivo </it>for low-LET treatments are moderate, with changes in the OER up to 11% for dose painting (1 or 3 Gy per fraction compared to 2 Gy) and up to 22% in hyper-/hypofractionation (0.5 or 20 Gy per fraction compared to 2 Gy) for oxygen tensions between 0.2 and 20 mmHg typically measured clinically in hypoxic tumors. For extremely hypoxic cells (0.01 mmHg), the dose dependence of the OER becomes more pronounced (up to 36%). For high LET, OER variations up to 4% for the whole range of oxygen tensions between 0.01 and 20 mmHg were found, which were much smaller than for low LET.</p> <p>Conclusions</p> <p>The formalism presented in this paper can be used for various tissue and radiation types to estimate OER variations with dose and help to decide in clinical practice whether some dose changes in dose painting or in fractionation can bring more benefit in terms of the OER in the treatment of a specific hypoxic tumor.</p

Coaching Models of School-Based Prevention and Promotion Programmes: A Qualitative Exploration of UK Teachers' Perceptions

There has been increased interest in recent years regarding the utility of imported universal prevention and promotion (P&P) programmes in UK schools, many of which have a coaching model attached. However, there have been relatively few studies exploring the cultural transferability and social validity of these models, even though evidence suggests that these factors are important to the successful implementation of the programmes, and thus the achievement of the intended outcomes. The aim of the current study was to explore the coaching practices that teachers report experiencing, and to further understanding of the perceived benefts of these coaching practices to teachers. The sample consisted of 33 teachers implementing one of two universal, school-based P&P programmes, Good Behavior Game and Promoting Alternative Thinking Strategies as part of large-scale, randomised controlled trials. Qualitative, semi-structured interviews were conducted, and data were analysed thematically utilising a hybrid approach. Teachers typically reported engaging in six distinct practices with their coaches. While the majority of these practices were in line with coaching literature, there were some discrepancies between intended coaching practices and teachers’ reports. The coaching practices were generally perceived to be acceptable to teachers. Two unanticipated practices, validation and motivation, appeared to be of particular value to teachers, although these are not currently a prominent feature in existing coaching models. The fndings provide implications for improving the development of socially valid coaching models for UK schools

Voting Characteristics of Individuals With Traumatic Brain Injury

Voting is the foundation of democracy. Limited data exist about voting characteristics of individuals with neurologic impairment including those living with a traumatic brain injury (TBI). To statistically examine voting characteristics using a convenience sample of registered voters with TBI during elections held in Mecklenburg County, North Carolina—2007, 2008. Data were collected on 51 participants with TBI during May 2007, 2008 general, and 2008 Presidential Election. (i) There was a significant difference between the Competence Assessment Tool for Voting (CAT‐V) total score of participants with TBI who voted and the CAT‐V total score of participants with TBI who did not vote and the CAT‐V total score predicted voting; (ii) the age of the participants with TBI was predictive of voting; and (iii) being married was inversely related to voting. We find that there is variation in voting even among this small sample interviewed for the present study, and that the variation is predictable. Those with the highest CAT‐Vs are most likely to vote. In addition, we find that traditional predictors of voting simply are not predictors among this TBI group, and even one, whether the person is married, has a negative effect on voting

What Podolsky, Einstein and Others Have Taught Me about Greatness

Continuing scientific progress often results in a focus on technological advancements while ignoring those scientists who have brought them to fruition. By ignoring the life stories and struggles of these scientists, generations of students are being deprived of insight that may serve to encourage them to enter the scientific fields. Furthermore, they may develop a perspective that suggests that these advancements occur with little personal or professional struggle. It is becoming increasingly common to compare scientists based upon their achievements. These comparisons could discourage students from entering the scientific disciplines by suggesting that contributions not equal to or surpassing those of the most celebrated scientists are essentially worthless. This results in a winner-take all attitude. This article details the experiences of one social scientist in his quest to develop a greater understanding of science, scientists and those characteristics that ultimately determine greatness

Game Theory and its Application to Penology

Game theory is the study of the interactions that occur between rational decision-makers and the dynamics that influence strategic behaviors. Paramount to this approach is the realization that an individual’s decisions are often influenced by the actions and/or anticipated actions of others. Of particular importance is Game Theory’s capacity to explain the prison’s disinterest and seeming inability to successfully promote offender rehabilitation. Herein the relationship existing between prisons and prisoners is viewed as a “game” designed to prevent an inmate “win”. As such, contemporary prisoners have (in protest) chosen to oppose all forms of correctional intervention even when doing so is personally detrimental. DOI: 10.5958/2347-6869.2018.00015.

Beyond the Millennium Development Goals: public health challenges in water and sanitation.

Over 1 billion people lack access to improved water sources and 2.6 billion lack access to appropriate sanitation, greatly contributing to the global burden of disease. The international community has committed to reducing by half the proportion of the world's population lacking access to water and sanitation as a part of the Millennium Development Goals (MDGs). However, the disease burden due to poor access, is borne primarily by the poorest countries and the poorest people within them. Simply reducing the proportion of people without adequate access will not automatically result in proportional reductions in the related disease burden. The public health challenge inherent in meeting the MDG targets is ensuring that improvements result in access to water and sanitation for the critical at-risk populations. Innovative approaches are required to ensure the availability of low-cost, simple, and locally acceptable water and sanitation interventions and integrating these approaches into existing social institutions, such as schools, markets, and health facilities