Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields

To limit toxicity to normal tissues adjacent to the target tumour volume, radiotherapy is delivered using fractionated regimes whereby the total prescribed dose is given as a series of sequential smaller doses separated by specific time intervals. The impact of fractionation on out-of-field survival and DNA damage responses was determined in AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells using uniform and modulated exposures delivered using a 225 kVp x-ray source. Responses to fractionated schedules (two equal fractions delivered with time intervals from 4 h to 48 h) were compared to those following acute exposures. Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures for the investigated cell lines. Specifically, there is a consistent lack of repair observed in the out-of-field populations during intervals between fractions, confirming the importance of cell signalling to out-of-field responses in a fractionated radiation schedule, and this needs to be confirmed for a wider range of cell lines and conditions.

Dynamics and structure of self-generated magnetics fields on solids following high contrast, high intensity laser irradiation

The dynamics of self-generated magnetic B-fields produced following the interaction of a high contrast, high intensity (I > 10¹⁹W cm^-2) laser beam with thin (3 μm thick) solid (Al or Au) targets is investigated experimentally and numerically. Two main sources drive the growth of B-fields on the target surfaces. B-fields are first driven by laser-generated hot electron currents that relax over ∼10-20 ps. Over longer timescales, the hydrodynamic expansion of the bulk of the target into vacuum also generates B-field induced by non-collinear gradients of density and temperature. The laser irradiation of the target front side strongly localizes the energy deposition at the target front, in contrast to the target rear side, which is heated by fast electrons over a much larger area. This induces an asymmetry in the hydrodynamic expansion between the front and rear target surfaces, and consequently the associated B-fields are found strongly asymmetric. The sole long-lasting (>30 ps) B-fields are the ones growing on the target front surface, where they remain of extremely high strength (∼8-10 MG). These B-fields have been recently put by us in practical use for focusing laser-accelerated protons [B. Albertazzi et al., Rev. Sci. Instrum. 86, 043502 (2015)]; here we analyze in detail their dynamics and structure.

Achieving optimal dose intensity with adjuvant chemotherapy in elderly breast cancer patients:A 10-year retrospective study in a UK institution

The study was to determine if breast cancer patients aged 65 and above could be given adjuvant chemotherapy safely while achieving an acceptable relative dose intensity of at least 85%. We identified all patients aged 65 and over who received adjuvant chemotherapy over the 10 year period, November 1999 to October 2009, and determined the proportion that achieved a relative dose intensity of at least 85% as well as the tolerability of their treatment. A total of 101 patients were identified, with a median age of 69 years (range 65-78).Of these, 25.7% of patients had at least one major comorbidity, 84.2% had a tumor size of 5 cm or less, 73.3% were node positive and 58.4% were hormone receptor positive. The chemotherapy regimens used were AC (Doxorubicin and Cyclophosphamide), FEC (Fluorouracil, Epirubicin, and Cyclophosphamide), CMF (Cyclophosphamide, Methotrexate, and Fluorouracil) and ECMF (Epirubicin followed by CMF). Seventy-nine patients (78.2%) achieved the relative dose intensity of at least 85%. With respect to toxicity, 11.9% of patients developed febrile neutropenia and 23.8% of patients required hospital admission during the treatment period, but there were no treatment-related deaths in the group. A significant proportion of patients aged 65 and above achieved the intended dose intensity of at least 85% over this 10-year period, with manageable toxicity levels. This supports the use of these regimens as adjuvant chemotherapy for breast cancer in this age group. © 2011 Wiley Periodicals, Inc.

Transverse Spreading of Electrons in High-Intensity Laser Fields

We show that for collisions of electrons with a high-intensity laser, discrete photon emissions introduce a transverse beam spread that is distinct from that due to classical (or beam shape) effects. Via numerical simulations, we show that this quantum induced transverse momentum gain of the electron is manifest in collisions with a realistic laser pulse of intensity within reach of current technology, and we propose it as a measurable signature of strong-field quantum electrodynamics.

The Creativity of Mothering: Intensity, Anxiety and Normative Accountability

This chapter focuses on the question of how to explain agency in the context of motherhood. In so doing, it seeks to go beyond the tendency to focus exclusively on the burden of coordination which institutional structures generate for mothers, in order to examine the evaluative burden which normative structures demand of this role. Drawing on interview material with 40 middle class mothers across two research sites in the UK and US, the paper develops a three-part typology of maternal role performance. This relies on the insights of contemporary action theory, with its emphasis on emotionally configured intersubjective interpretation of normative structures, and more specifically on Joas’s pragmatist theorisation of social action as a creative process. The paper argues that maternal agency takes three distinct ideal-typical forms, namely romantic expressivism, rational instrumentalism, and pragmatism. These are conceived as distinct creative responses to the evaluative demands of motherhood, as the agents go about interpreting situated norms, needs and interests.

Ultrafast charge dynamics initiated by high-intensity, ultrashort laser-matter interaction

The interaction of high‐intensity laser pulses with matter releases instantaneously ultra‐large currents of highly energetic electrons, leading to the generation of highly‐transient, large‐amplitude electric and magnetic fields. We report results of recent experiment in which such charge dynamics have been studied by using proton probing techniques able to provide maps of the electrostatic fields with high spatial and temporal resolution. The dynamics of ponderomotive channelling in underdense plasmas have been studied in this way, as also the processes of Debye sheath formation and MeV ion front expansion at the rear of laser‐irradiated thin metallic foils. An application employing laser‐driven impulsive fields for energy‐selective ion beam focusing is also presented.

Responding to mental health statutory drivers: experience of a low intensity cognitive behavioural therapy programme

Objectives Stress control (SC), a brief psycho-education course, was implemented to increase access to psychological therapies in line with Northern Irish mental health service statutory drivers. The first aim of this study was to gauge the efficacy of SC in a robust manner with clinical significance testing. The second aim was to assess whether demographics traditionally ‘hard-to-reach’ – males, younger adults and those from deprived areas – accessed SC. The third aim was to elucidate what prompted their access and the experiences of attendees at SC. Methods Attendees at SC were 170 adults over six iterations of the course. Pre- and post-questionnaires included the Depression Anxiety Stress Scales – 21, captured demographic details and qualitative feedback, which was subject to a mixed-methods analysis. Results SC attendees reported significant decreases on depression, anxiety and stress sub-scales post-intervention. Moreover, 38.71% ( n =36) of attendees who completed SC exhibited clinically significant improvement afterwards on one or more sub-scale. Attendance figures for males, younger adults and those classified as socioeconomically deprived were modest. Patterns within the data suggested prospective success for targeting these cohorts. Conclusions SC attracted people in need of mental healthcare input and affected quantifiable change within those people’s lives, while satisfying statutory demands for service delivery in an accessible community context. Recommendations to increase engagement with those traditionally ‘hard-to-reach’ for psychological services are provided, which, if implemented, have the potential to achieve further compliance with Northern Irish mental health statutory drivers.

Helium line intensity ratio in microwave-generated plasmas

The line intensity ratio method provides a nonintrusive diagnostic for the measurement of electron temperature in microwave-generated plasmas. For optically thin plasmas of low density, a line intensity method using He I lines can often be used, and is based on the fact that the electron impact excitation rate coefficients for helium singlet and triplet states are insensitive to electron density but differ as a function of the electron temperature. Line intensity measurements are presented from microwave-generated helium plasmas. Both steady-state corona and collision-radiative theoretical models are used to evaluate the ground and excited state populations. The line ratio versus electron temperature obtained from both of these methods are compared with the results from measurements. However, it is not possible to diagnose the electron temperature from the line ratios alone due to the presence of significant opacity and nonnegligible 1s2s S-3 metastable fraction in the plasma. (C) 2004 American Institute of Physics.

Protocol for the isotoxic intensity modulated radiotherapy (IMRT) in stage III non-small cell lung cancer (NSCLC): a feasibility study.

Introduction The majority of stage III patients with non-small cell lung cancer (NSCLC) are unsuitable for concurrent chemoradiotherapy, the non-surgical gold standard of care. As the alternative treatment options of sequential chemoradiotherapy and radiotherapy alone are associated with high local failure rates, various intensification strategies have been employed. There is evidence to suggest that altered fractionation using hyperfractionation, acceleration, dose escalation, and individualisation may be of benefit. The MAASTRO group have pioneered the concept of ‘isotoxic’ radiotherapy allowing for individualised dose escalation using hyperfractionated accelerated radiotherapy based on predefined normal tissue constraints. This study aims to evaluate whether delivering isotoxic radiotherapy using intensity modulated radiotherapy (IMRT) is achievable.

Methods and analysis Isotoxic IMRT is a multicentre feasibility study. From June 2014, a total of 35 patients from 7 UK centres, with a proven histological or cytological diagnosis of inoperable NSCLC, unsuitable for concurrent chemoradiotherapy will be recruited. A minimum of 2 cycles of induction chemotherapy is mandated before starting isotoxic radiotherapy. The dose of radiation will be increased until one or more of the organs at risk tolerance or the maximum dose of 79.2 Gy is reached. The primary end point is feasibility, with accrual rates, local control and overall survival our secondary end points. Patients will be followed up for 5 years.

Ethics and dissemination The study has received ethical approval (REC reference: 13/NW/0480) from the National Research Ethics Service (NRES) Committee North West—Greater Manchester South. The trial is conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP). The trial results will be published in a peer-reviewed journal and presented internationally.

Trial registration number NCT01836692; Pre-results.

Efficacy and Acceptability of Reduced Intensity Constraint-Induced Movement Therapy for Children Aged 9–11 years with Hemiplegic Cerebral Palsy: A Pilot Study

OBJECTIVE: Assess efficacy and acceptability of reduced intensity constraint-induced movement therapy (CIMT) in children with cerebral palsy (CP).

METHODS: Single-subject research design and semi-structured interviews. Children (9-11y) with hemiplegia underwent five baseline assessments followed by two weeks CIMT. Six further assessments were performed during treatment and follow-up phases. The primary outcome was the Melbourne Assessment of Unilateral Upper Limb Function (MUUL). Quantitative data were analysed using standard single-subject methods and qualitative data by thematic analysis.

RESULTS: Four of the seven participants demonstrated statistically significant improvements in MUUL (3-11%, p < .05). Two participants achieved significant improvements in active range of motion but strength and tone remained largely unchanged. Qualitative interviews highlighted limitations of the restraint, importance of family involvement, and coordination of treatment with education.

CONCLUSIONS: Reduced intensity CIMT may be effective for some children in this population; however it is not suitable for all children with hemiplegia.

SWORD: an intelligent vibratory wearable device to improve rehabilitation in stroke patients

Anualmente ocorrem cerca de 16 milhões AVCs em todo o mundo. Cerca de metade dos sobreviventes irá apresentar défice motor que necessitará de reabilitação na janela dos 3 aos 6 meses depois do AVC. Nos países desenvolvidos, é estimado que os custos com AVCs representem cerca de 0.27% do Produto Interno Bruto de cada País. Esta situação implica um enorme peso social e financeiro. Paradoxalmente a esta situação, é aceite na comunidade médica a necessidade de serviços de reabilitação motora mais intensivos e centrados no doente. Na revisão do estado da arte, demonstra-se o arquétipo que relaciona metodologias terapêuticas mais intensivas com uma mais proficiente reabilitação motora do doente. Revelam-se também as falhas nas soluções tecnológicas existentes que apresentam uma elevada complexidade e custo associado de aquisição e manutenção. Desta forma, a pergunta que suporta o trabalho de doutoramento seguido inquire a possibilidade de criar um novo dispositivo de simples utilização e de baixo custo, capaz de apoiar uma recuperação motora mais eficiente de um doente após AVC, aliando intensidade com determinação da correcção dos movimentos realizados relativamente aos prescritos. Propondo o uso do estímulo vibratório como uma ferramenta proprioceptiva de intervenção terapêutica a usar no novo dispositivo, demonstra-se a tolerabilidade a este tipo de estímulos através do teste duma primeira versão do sistema apenas com a componente de estimulação num primeiro grupo de 5 doentes. Esta fase validará o subsequente desenvolvimento do sistema SWORD. Projectando o sistema SWORD como uma ferramenta complementar que integra as componentes de avaliação motora e intervenção proprioceptiva por estimulação, é descrito o desenvolvimento da componente de quantificação de movimento que o integra. São apresentadas as diversas soluções estudadas e o algoritmo que representa a implementação final baseada na fusão sensorial das medidas provenientes de três sensores: acelerómetro, giroscópio e magnetómetro. O teste ao sistema SWORD, quando comparado com o método de reabilitação tradicional, mostrou um ganho considerável de intensidade e qualidade na execução motora para 4 dos 5 doentes testados num segundo grupo experimental. É mostrada a versatilidade do sistema SWORD através do desenvolvimento do módulo de Tele-Reabilitação que complementa a componente de quantificação de movimento com uma interface gráfica de feedback e uma ferramenta de análise remota da evolução motora do doente. Finalmente, a partir da componente de quantificação de movimento, foi ainda desenvolvida uma versão para avaliação motora automatizada, implementada a partir da escala WMFT, que visa retirar o factor subjectivo da avaliação humana presente nas escalas de avaliação motora usadas em Neurologia. Esta versão do sistema foi testada num terceiro grupo experimental de cinco doentes.

Spiking neural network model of sound localisation using the interaural intensity difference

In this paper, a spiking neural network (SNN) architecture to simulate the sound localization ability of the mammalian auditory pathways using the interaural intensity difference cue is presented. The lateral superior olive was the inspiration for the architecture, which required the integration of an auditory periphery (cochlea) model and a model of the medial nucleus of the trapezoid body. The SNN uses leaky integrateand-fire excitatory and inhibitory spiking neurons, facilitating synapses and receptive fields. Experimentally derived headrelated transfer function (HRTF) acoustical data from adult domestic cats were employed to train and validate the localization ability of the architecture, training used the supervised learning algorithm called the remote supervision method to determine the azimuthal angles. The experimental results demonstrate that the architecture performs best when it is localizing high-frequency sound data in agreement with the biology, and also shows a high degree of robustness when the HRTF acoustical data is corrupted by noise.

Traços de personalidade, estados emocionais e condução : um estudo comparativo entre condutores de ambos os sexos

Tese de doutoramento, Ciências e Tecnologias da Saúde (Desenvolvimento Humano e Social), Universidade de Lisboa, Faculdade de Medicina, 2014

Can illusory deviant stimuli be used as attentional distractors to record vMMN in a passive three stimulus oddball paradigm?

A passive three stimulus oddball paradigm was used to investigate Visual Mismatch Negativity (vMMN) a component of the Event Related Potential (ERP) believed to represent a central pre-attentive change mechanism. Responses to a change in orientation were recorded to monochrome stimuli presented to subjects on a computer screen. One of the infrequent stimuli formed an illusory figure (Kanizsa Square) aimed to capture spatial attention in the absence of an active task. Nineteen electrodes (10-20 system) were used to record the electroencephalogram in fourteen subjects (ten females) mean age 34.5 years. ERPs to all stimuli consisted of a positive negative positive complex recorded maximally over lateral occipital areas. The negative component was greater for deviant and illusory deviant compared to standard stimuli in a time window of 170-190 ms. A P3a component over frontal/central electrodes to the illusory deviant but not to the deviant stimulus suggests the illusory figure was able to capture attention and orientate subjects to the recording. Subtraction waveforms revealed visual discrimination responses at occipital electrodes, which may represent vMMN. In a control study with 13 subjects (11 females; mean age 29.23 years), using an embedded active attention task, we confirmed the existence of an earlier (150-170 ms) and attenuated vMMN. Recordings from an intracranial case study confirmed separation of N1 and discrimination components to posterior and anterior occipital areas, respectively. We conclude that although the illusory figure captured spatial attention in its own right it did not draw sufficient attentional resources from the standard-deviant comparison as revealed when using a concurrent active task.

Using an anisotropic semivariogram of acoustic backscatter intensity to determine the effects of river and tidal forces on the spatial structure of the Gold River delta

Senior thesis written for Oceanography 445