Writing the History of the British Stage, 1660-1900

A monograph on British theatre historiography from its emergence in the Restoration to its foundation as an academic discipline in the early 20th century.

All the World's a Stage: Facilitating Discovery Science and Improved Cancer Care through the Global Alliance for Genomics and Health

The recent explosion of genetic and clinical data generated from tumor genome analysis presents an unparalleled opportunity to enhance our understanding of cancer, but this opportunity is compromised by the reluctance of many in the scientific community to share datasets and the lack of interoperability between different data platforms. The Global Alliance for Genomics and Health is addressing these barriers and challenges through a cooperative framework that encourages "team science" and responsible data sharing, complemented by the development of a series of application program interfaces that link different data platforms, thus breaking down traditional silos and liberating the data to enable new discoveries and ultimately benefit patients.

A comparison between accelerated hypofractionation and stereotactic ablative radiotherapy (SABR) for early-stage non-small cell lung cancer (NSCLC): Results of a propensity score-matched analysis

BACKGROUND AND PURPOSE: Stereotactic ablative radiotherapy (SABR) has become standard for inoperable early-stage non-small cell lung cancer (NSCLC). However, there is no randomized evidence demonstrating benefit over more fractionated radiotherapy. We compared accelerated hypofractionation (AH) and SABR using a propensity score-matched analysis.

MATERIALS AND METHODS: From 1997-2007, 119 patients (T1-3N0M0 NSCLC) were treated with AH (48-60Gy, 12-15 fractions). Prior to SABR, this represented our institutional standard. From 2008-2012, 192 patients (T1-3N0M0 NSCLC) were treated with SABR (48-52Gy, 4-5 fractions). A total of 114 patients (57 per cohort) were matched (1:1 ratio, caliper: 0.10) using propensity scores.

RESULTS: Median follow-up (range) for the AH cohort was 36.3 (2.5-109.1) months, while that for the SABR group was 32.5 (0.3-62.6)months. Three-year overall survival (OS) and local control (LC) rates were 49.5% vs. 72.4% [p=0.024; hazard ratio (HR): 2.33 (1.28, 4.23), p=0.006] and 71.9% vs. 89.3% [p=0.077; HR: 5.56 (1.53, 20.2), p=0.009], respectively. On multivariable analysis, tumour diameter and PET staging were predictive for OS, while the only predictive factor for LC was treatment cohort.

CONCLUSIONS: OS and LC were improved with SABR, although OS is more closely related to non-treatment factors. This represents one of the few studies comparing AH to SABR for early-stage lung cancer.

Comprehensive numerical modelling of the performance of a second harmonic generation stage coupled with a low-gain optical parametric amplifier

We present a comprehensive model for predicting the full performance of a second harmonic generation-optical parametric amplification system that aims at enhancing the temporal contrast of laser pulses. The model simultaneously takes into account all the main parameters at play in the system such as the group velocity mismatch, the beam divergence, the spectral content, the pump depletion, and the length of the nonlinear crystals. We monitor the influence of the initial parameters of the input pulse and the interdependence of the two related non-linear processes on the performance of the system and show its optimum configuration. The influence of the initial beam divergence on the spectral and the temporal characteristics of the generated pulse is discussed. In addition, we show that using a crystal slightly longer than the optimum length and introducing small delay between the seed and the pump ensures maximum efficiency and compensates for the spectral shift in the optical parametric amplification stage in case of chirped input pulse. As an example, calculations for bandwidth transform limited and chirped pulses of sub-picosecond duration in beta barium borate crystal are presented.

The Virgin Father (Revival of 2009 production):The Virgin Father: A Stage Play (Revival of 2009 production)

A stage play touring Cushendall, Down Arts Centre, The Playhouse Derry/Londonderry, with a further one-week run at the Lyric Theatre, Belfast.

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.

Immune-derived PD-L1 gene expression defines a subgroup of stage II/III colorectal cancer patients with favorable prognosis that may be harmed by adjuvant chemotherapy

A recent phase 2 study of metastatic colorectal carcinoma (CRC) patients showed that mismatch repair gene status was predictive of clinical response to PD-1-targeting immune checkpoint blockade. Further examination revealed strong correlation between PD-L1 protein expression and microsatellite instability (MSI) in stage IV CRC, suggesting that the amount of PD-L1 protein expression could identify late stage patients who may benefit from immunotherapy. To assess whether the clinical associations between PD-L1 gene expression and MSI identified in metastatic CRC are also present in stage II/III CRC, we used in silico analysis to elucidate the cell types expressing the PD-L1 gene. We found a significant association of PD-L1 gene expression with MSI in early stage CRC (P < 0.001) and show that unlike in non-CRC tumors, PD-L1 is derived predominantly from the immune infiltrate. We demonstrate that PD-L1 gene expression has positive prognostic value in the adjuvant disease setting (PD-L1low v PD-L1high HR = 9.09; CI, 2.11-39.10). PD-L1 gene expression had predictive value, as patients with high PD-L1 expression appear to be harmed by standard-of-care treatment (HR = 4.95; CI,1.10-22.35). Building on the promising results from the metastatic CRC PD-1-targeting trial, we provide compelling evidence that PD-L1high/MSI/immunehigh stage II/III CRC patients should not receive standard chemotherapy. This conclusion supports the rationale to clinically evaluate this patient subgroup for PD-1 blockade treatment.

Local object gist: meaningful shapes and spatial layout at a very early stage of visual processing

In his introduction, Pinna (2010) quoted one of Wertheimer’s observations: “I stand at the window and see a house, trees, sky. Theoretically I might say there were 327 brightnesses and nuances of color. Do I have ‘327’? No. I have sky, house, and trees.” This seems quite remarkable, for Max Wertheimer, together with Kurt Koffka and Wolfgang Koehler, was a pioneer of Gestalt Theory: perceptual organisation was tackled considering grouping rules of line and edge elements in relation to figure-ground segregation, i.e., a meaningful object (the figure) as perceived against a complex background (the ground). At the lowest level – line and edge elements – Wertheimer (1923) himself formulated grouping principles on the basis of proximity, good continuation, convexity, symmetry and, often forgotten, past experience of the observer. Rubin (1921) formulated rules for figure-ground segregation using surroundedness, size and orientation, but also convexity and symmetry. Almost a century of research into Gestalt later, Pinna and Reeves (2006) introduced the notion of figurality, meant to represent the integrated set of properties of visual objects, from the principles of grouping and figure-ground to the colour and volume of objects with shading. Pinna, in 2010, went one important step further and studied perceptual meaning, i.e., the interpretation of complex figures on the basis of past experience of the observer. Re-establishing a link to Wertheimer’s rule about past experience, he formulated five propositions, three definitions and seven properties on the basis of observations made on graphically manipulated patterns. For example, he introduced the illusion of meaning by comics-like elements suggesting wind, therefore inducing a learned interpretation. His last figure shows a regular array of squares but with irregular positions on the right side. This pile of (ir)regular squares can be interpreted as the result of an earthquake which destroyed part of an apartment block. This is much more intuitive, direct and economic than describing the complexity of the array of squares.

Évolution de l'identité professionnelle d'étudiantes de niveaux collégial et universitaire dans le contexte de la réalisation d'un stage en milieu de garde québécois ou international

La présente étude a comme objectif d'évaluer l'impact du stage pratique comme situation d'apprentissage dans le développement de l'identité professionnelle. Le cadre conceptuel fait référence à une perspective interactionniste où transige une dialectique entre le sujet et le monde de la socialisation professionnelle: donc, d'une identité négociée en fonction des valeurs du milieu d'éducation et des intérêts de l'individu. Des mesures de ce construit sont prises en compte avant et après la réalisation du stage, puis sont comparées au construit collectif associé aux milieux de stage. Le choix méthodologique s'est porté vers la méthode Q qui s'avère une approche compatible avec l'étude des systèmes de valeurs des individus (Stephenson, 1953). Ainsi, la technique du Q-Sort consiste en une priorisation impliquant un tri d'énoncés de nature qualitative. Le traitement statistique permet ensuite d'examiner l'interrelation d'attitudes individuelles privilégiées par un groupe de répondants. L'échantillon se compose de stagiaires en milieux de garde du collégial (n= ll), de niveau universitaire (n=12) et d'éducatrices (n=81 ) provenant du Québec, de la France, de la Belgique et du Mali. Le Q-sort se compose de 79 énoncés distribués selon une répartition quasi-normale à choix forcés dans sept catégories. L'analyse statistique porte sur les matrices inversées de données afin d'évaluer le degré de rapprochement entre les individus dans la priorisation des valeurs en se basant sur les corrélations et les analyses factorielles. Les résultats mettent en évidence le degré de rapprochement entre les systèmes de valeurs des éducatrices québécoises et ceux des intervenants des autres pays. Quant à l'impact du stage sur les étudiantes, celui-ci se traduit par un éloignement, un rapprochement ou un maintien aux valeurs des éducatrices des milieux de garde. L'étude démontre qu'il s'avère possible d'évaluer l'impact de la formation pratique sur les valeurs liées à l'identité professionnelle tant sur le plan qualitatif que quantitatif.