Investigating the influence of respiratory motion on the radiation induced bystander effect in modulated radiotherapy

Respiratory motion introduces complex spatio-temporal variations in the dosimetry of radiotherapy and may contribute towards uncertainties in radiotherapy planning. This study investigates the potential radiobiological implications occurring due to tumour motion in areas of geometric miss in lung cancer radiotherapy. A bespoke phantom and motor-driven platform to replicate respiratory motion and study the consequences on tumour cell survival in vitro was constructed. Human non-small-cell lung cancer cell lines H460 and H1299 were irradiated in modulated radiotherapy configurations in the presence and absence of respiratory motion. Clonogenic survival was calculated for irradiated and shielded regions. Direction of motion, replication of dosimetry by multi-leaf collimator (MLC) manipulation and oscillating lead shielding were investigated to confirm differences in cell survival. Respiratory motion was shown to significantly increase survival for out-of-field regions for H460/H1299 cell lines when compared with static irradiation (p <0.001). Significantly higher survival was found in the in-field region for the H460 cell line (p <0.030). Oscillating lead shielding also produced these significant differences. Respiratory motion and oscillatory delivery of radiation dose to human tumour cells has a significant impact on in- and out-of-field survival in the presence of non-uniform irradiation in this in vitro set-up. This may have important radiobiological consequences for modulated radiotherapy in lung cancer. 

Investigating the Potential Impact of Four-dimensional Computed Tomography (4DCT) on Toxicity, Outcomes and Dose Escalation for Radical Lung Cancer Radiotherapy

AIMS: To investigate the potential dosimetric and clinical benefits predicted by using four-dimensional computed tomography (4DCT) compared with 3DCT in the planning of radical radiotherapy for non-small cell lung cancer.

MATERIALS AND METHODS:
Twenty patients were planned using free breathing 4DCT then retrospectively delineated on three-dimensional helical scan sets (3DCT). Beam arrangement and total dose (55 Gy in 20 fractions) were matched for 3D and 4D plans. Plans were compared for differences in planning target volume (PTV) geometrics and normal tissue complication probability (NTCP) for organs at risk using dose volume histograms. Tumour control probability and NTCP were modelled using the Lyman-Kutcher-Burman (LKB) model. This was compared with a predictive clinical algorithm (Maastro), which is based on patient characteristics, including: age, performance status, smoking history, lung function, tumour staging and concomitant chemotherapy, to predict survival and toxicity outcomes. Potential therapeutic gains were investigated by applying isotoxic dose escalation to both plans using constraints for mean lung dose (18 Gy), oesophageal maximum (70 Gy) and spinal cord maximum (48 Gy).

RESULTS:
4DCT based plans had lower PTV volumes, a lower dose to organs at risk and lower predicted NTCP rates on LKB modelling (P < 0.006). The clinical algorithm showed no difference for predicted 2-year survival and dyspnoea rates between the groups, but did predict for lower oesophageal toxicity with 4DCT plans (P = 0.001). There was no correlation between LKB modelling and the clinical algorithm for lung toxicity or survival. Dose escalation was possible in 15/20 cases, with a mean increase in dose by a factor of 1.19 (10.45 Gy) using 4DCT compared with 3DCT plans.

CONCLUSIONS:
4DCT can theoretically improve therapeutic ratio and dose escalation based on dosimetric parameters and mathematical modelling. However, when individual characteristics are incorporated, this gain may be less evident in terms of survival and dyspnoea rates. 4DCT allows potential for isotoxic dose escalation, which may lead to improved local control and better overall survival.

Mature students – participation in maths support and progression

Maths support at the Learning Development Service takes the form of drop-in contact, one-to-one appointments and workshops. Analysis over three years from 2010/11 to 2012/13 shows that 45% of one-to-one appointments involved a mature student, defined at Queen’s University Belfast (QUB) as one who has had a break in full-time study (normally a minimum of two years). This is a very high proportion given that 4% of students at QUB are mature. Considering engineering undergraduates only, the fraction of one-to-one appointments involving mature students was also 45%. This study can report a wide variation in terms of progression of mature students in engineering and aims to consider how more traditional undergraduate learners could be persuaded to adopt the attitudes of mature students in partaking of maths support.

Abstinence from alcohol may indeed be the best policy: 32 month longitudinal outcomes among adolescents in the United Kingdom.

The present study investigated the longitudinal relationship between alcohol consumption at age 13, and at age 16. Alcohol-specific measures were frequency of drinking, amount consumed at last use and alcohol related harms. Self-report data were gathered from 1113 high school students at T1, and 981 students at T2. Socio-demographic data were gathered, as was information on context of use, alcohol-related knowledge and attitudes, four domains of aggression and delay reward discounting. Results indicated that any consumption of alcohol, even supervised consumption, at T1 was associated with significantly poorer outcomes at T2. In other words, compared to those still abstinent at age 13, those engaging in alcohol use in any context reported significantly more frequent drinking, more alcohol-related harms and more units consumed at last use at age 16. Results also support the relationship between higher levels of physical aggression at T1 and a greater likelihood of more problematic alcohol use behaviours at T2. The findings support other evidence suggesting that abstinence in early adolescence has better longitudinal outcomes that supervised consumption of alcohol. These results suggest support for current guidance on adolescent drinking in the United Kingdom (UK).

Understanding macroalgal dispersal in a complex hydrodynamic environment: a combined population genetic and physical modelling approach

Gene flow in macroalgal populations can be strongly influenced by spore or gamete dispersal. This, in turn, is influenced by a convolution of the effects of current flow and specific plant reproductive strategies. Although several studies have demonstrated genetic variability in macroalgal populations over a wide range of spatial scales, the associated current data have generally been poorly resolved spatially and temporally. In this study, we used a combination of population genetic analyses and high-resolution hydrodynamic modelling to investigate potential connectivity between populations of the kelp Laminaria digitata in the Strangford Narrows, a narrow channel characterized by strong currents linking the large semi-enclosed sea lough, Strangford Lough, to the Irish Sea. Levels of genetic structuring based on six microsatellite markers were very low, indicating high levels of gene flow and a pattern of isolation-by-distance, where populations are more likely to exchange migrants with geographically proximal populations, but with occasional long-distance dispersal. This was confirmed by the particle tracking model, which showed that, while the majority of spores settle near the release site, there is potential for dispersal over several kilometres. This combined population genetic and modelling approach suggests that the complex hydrodynamic environment at the entrance to Strangford Lough can facilitate dispersal on a scale exceeding that proposed for L. digitata in particular, and the majority of macroalgae in general. The study demonstrates the potential of integrated physical–biological approaches for the prediction of ecological changes resulting from factors such as anthropogenically induced coastal zone changes.

Investigation into the radiobiological consequences of pre-treatment verification imaging with megavoltage X-rays in radiotherapy

Objective: The aim of this study was to investigate the effect of pre-treatment verification imaging with megavoltage (MV) X-rays on cancer and normal cell survival in vitro and to compare the findings with theoretically modelled data. Since the dose received from pre-treatment imaging can be significant, incorporation of this dose at the planning stage of treatment has been suggested.

Methods: The impact of imaging dose incorporation on cell survival was investigated by clonogenic assay, irradiating DU-145 prostate cancer, H460 non-small cell lung cancer and AGO-1522b normal tissue fibroblast cells. Clinically relevant imaging-to-treatment times of 7.5 minutes and 15 minutes were chosen for this study. The theoretical magnitude of the loss of radiobiological efficacy due to sublethal damage repair was investigated using the Lea-Catcheside dose protraction factor model.

Results: For the cell lines investigated, the experimental data showed that imaging dose incorporation had no significant impact upon cell survival. These findings were in close agreement with the theoretical results.

Conclusions: For the conditions investigated, the results suggest that allowance for the imaging dose at the planning stage of treatment should not adversely affect treatment efficacy.

Advances in Knowledge: There is a paucity of data in the literature on imaging effects in radiotherapy. This paper presents a systematic study of imaging dose effects on cancer and normal cell survival, providing both theoretical and experimental evidence for clinically relevant imaging doses and imaging-to-treatment times. The data provide a firm foundation for further study into this highly relevant area of research.

Generation of neutral and high-density electron–positron pair plasmas in the laboratory

Electron–positron pair plasmas represent a unique state of matter, whereby there exists an intrinsic and complete symmetry between negatively charged (matter) and positively charged (antimatter) particles. These plasmas play a fundamental role in the dynamics of ultra-massive astrophysical objects and are believed to be associated with the emission of ultra-bright gamma-ray bursts. Despite extensive theoretical modelling, our knowledge of this state of matter is still speculative, owing to the extreme difficulty in recreating neutral matter–antimatter plasmas in the laboratory. Here we show that, by using a compact laser-driven setup, ion-free electron–positron plasmas with unique characteristics can be produced. Their charge neutrality (same amount of matter and antimatter), high-density and small divergence finally open up the possibility of studying electron–positron plasmas in controlled laboratory experiments.

Laser-driven generation of collimated ultra-relativistic positron beams

We report on recent experimental results concerning the generation of collimated (divergence of the order of a few mrad) ultra-relativistic positron beams using a fully optical system. The positron beams are generated exploiting a quantum-electrodynamic cascade initiated by the propagation of a laser-accelerated, ultra-relativistic electron beam through high-Z solid targets. As long as the target thickness is comparable to or smaller than the radiation length of the material, the divergence of the escaping positron beam is of the order of the inverse of its Lorentz factor. For thicker solid targets the divergence is seen to gradually increase, due to the increased number of fundamental steps in the cascade, but it is still kept of the order of few tens of mrad, depending on the spectral components in the beam. This high degree of collimation will be fundamental for further injection into plasma-wakefield afterburners.

Motion Management for Radical Radiotherapy in Non-small Cell Lung Cancer

Intrafraction tumour motion is an issue that is of increased interest in the era of image-guided radiotherapy. It is particularly relevant for non-small cell lung cancer, for which a number of recent developments are in use to aid with motion management in the delivery of radical radiotherapy. The ability to deliver hypofractionated ablative doses, such as in stereotactic radiotherapy, has been aided by improvements in the ability to analyse tumour motion and amend treatment delivery. In addition, accounting for tumour motion can enable dose escalation to occur by reducing the normal tissue being irradiated by virtue of a reduction in target volumes. Motion management for lung tumours incorporates five key components: imaging, breath-hold techniques, abdominal compression, respiratory tracking and respiratory gating. These will be described, together with the relevant benefits and associated complexities. Many studies have described improved dosimetric coverage and reduced normal tissue complication probability rates when using motion management techniques. Despite the widespread uptake of many of these techniques, there is a paucity of literature reporting improved outcome in overall survival and local control for patients whenever motion management techniques are used. This overview will review the extent of lung tumour motion, ways in which motion is detected and summarise the key methods used in motion management.

A-level Mathematics Module Choice and Subsequent Performance in First Year of an Engineering Degree

The A-level Mathematics qualification is based on a compulsory set of pure maths modules and a selection of applied maths modules. The flexibility in choice of applied modules has led to concerns that many students would proceed to study engineering at university with little background in mechanics. A survey of aerospace and mechanical engineering students in our university revealed that a combination of mechanics and statistics (the basic module in both) was by far the most popular choice of optional modules in A-level Mathematics, meaning that only about one-quarter of the class had studied mechanics beyond the basic module within school mathematics. Investigation of student performance in two core, first-year engineering courses, which build on a mechanics foundation, indicated that any benefits for students who studied the extra mechanics at school were small. These results give concern about the depth of understanding in mechanics gained during A-level Mathematics.

Mathematics background of engineering students in Northern Ireland and Finland

The Organisation for Economic Co-operation and Development investigated numeracy proficiency among adults of working age in 23 countries across the world. Finland had the highest mean numeracy proficiency for people in the 16 – 24 age group while Northern Ireland’s score was below the mean for all the countries. An international collaboration has been undertaken to investigate the prevalence of mathematics within the secondary education systems in Northern Ireland and Finland, to highlight particular issues associated with transition into university and consider whether aspects of the Finnish experience are applicable elsewhere. In both Northern Ireland and Finland, at age 16, about half of school students continue into upper secondary level following their compulsory education. The upper secondary curriculum in Northern Ireland involves a focus on three subjects while Finnish students study a very wide range of subjects with about two-thirds of the courses being compulsory. The number of compulsory courses in maths is proportionally large; this means that all upper secondary pupils in Finland (about 55% of the population) follow a curriculum which has a formal maths content of 8%, at the very minimum. In contrast, recent data have indicated that only about 13% of Northern Ireland school leavers studied mathematics in upper secondary school. The compulsory courses of the advanced maths syllabus in Finland are largely composed of pure maths with a small amount of statistics but no mechanics. They lack some topics (for example, in advanced calculus and numerical methods for integration) which are core in Northern Ireland. This is not surprising given the much broader curriculum within upper secondary education in Finland. In both countries, there is a wide variation in the mathematical skills of school leavers. However, given the prevalence of maths within upper secondary education in Finland, it is to be expected that young adults in that country demonstrate high numeracy proficiency.

Interpreting A-level Mathematics grades – as easy as A, B, C?

Many concerns have been expressed that students’ basic mathematical skills have deteriorated during the 1990s and there has been disquiet that current A-level grading does not distinguish adequately between the more able students. This study reports the author’s experiences of teaching maths to large classes of first-year engineering students and aims to enhance understanding of levels of mathematical competence in more recent years. Over the last four years, the classes have consisted of a very large proportion of highly qualified students – about 91% of them had at least grade B in A-level Mathematics. With a small group of students having followed a non-traditional route to university (no A-level maths) and another group having benefitted through taking A-level Further Mathematics at school, the classes have contained a very wide range of mathematical backgrounds. Despite the introductory maths course at university involving mainly repetition of A-level material, students’ marks were spread over a very wide range – for example, A-level Mathematics grade B students have scored across the range 16 – 97%. Analytical integration is the topic which produced the largest variation in performance across the class but, in contrast, the A-level students generally performed well in differentiation. Initial analysis suggests some stability in recent years in the mathematical proficiency of students with a particular A-level Mathematics grade. Allowing choice of applied maths modules as part of the A-level maths qualification increases the variety of students’ mathematical backgrounds and their selection from mechanics, statistics or decision maths is not clear from the final qualification.

Developing mathematics support for first-year engineering students with non-traditional mathematics backgrounds

A maths support system for first-year engineering students with non-traditional entry qualifications has involved students working through practice questions structured to correspond with the maths module which runs in parallel. The setting was informal and there was significant one-to-one assistance. The non-traditional students (who are known to be less well prepared mathematically) were explicitly contacted in the first week of their university studies regarding the maths support and they generally seemed keen to participate. However, attendance at support classes was relatively low, on average, but varied greatly between students. Students appreciated the personal help and having time to ask questions. It seemed that having a small group of friends within the class promoted attendance – perhaps the mutual support or comfort that they all had similar mathematical difficulties was a factor. The classes helped develop confidence. Attendance was hindered by the class being timetabled too soon after the relevant lecture and students were reluctant to come with no work done beforehand. Although students at risk due to their mathematical unpreparedness can easily be identified at an early stage of their university career, encouraging them to partake of the maths support is an ongoing, major problem.