A general reaction-diffusion model of acidity in cancer invasion

We model the metabolism and behaviour of a developing cancer tumour in the context of its microenvironment, with the aim of elucidating the consequences of altered energy metabolism. Of particular interest is the Warburg Effect, a widespread preference in tumours for cytosolic glycolysis rather than oxidative phosphorylation for glucose breakdown, as yet incompletely understood. We examine a candidate explanation for the prevalence of the Warburg Effect in tumours, the acid-mediated invasion hypothesis, by generalising a canonical non-linear reaction–diffusion model of acid-mediated tumour invasion to consider additional biological features of potential importance. We apply both numerical methods and a non-standard asymptotic analysis in a travelling wave framework to obtain an explicit understanding of the range of tumour behaviours produced by the model and how fundamental parameters govern the speed and shape of invading tumour waves. Comparison with conclusions drawn under the original system—a special case of our generalised system—allows us to comment on the structural stability and predictive power of the modelling framework

Adapting a communication coaching intervention for obstetric sonographers delivering unexpected news: A qualitative study

Introduction: Despite widespread recognition that communicating unexpected news during obstetric ultrasound examinations is challenging, there is a dearth of research investigating how to teach evidence-based communication to sonographers. Communication Coaching is a supportive, positive method that has previously been associated with improvements in communication, patient satisfaction, and reduced burnout in clinicians. However, to date, no study has coached sonographers. This study explored stakeholders’ views on a proposed Communication Coaching intervention and used these data to adapt the intervention for use with qualified obstetric sonographers. Methods: Semi-structured interviews were conducted with people who have a vested interest in unexpected news delivery and thematic analysis was conducted on the data. Eight sonographers, six people with lived experience of receiving unexpected news and six representatives from third-sector organisations who support expectant parents were recruited (18 women; 2 men, aged between 21 and 75 years). Results: Participants viewed the planned Communication Coaching intervention favourably and suggested adaptations. The two main themes were (1) the practicalities of coaching, and (2) content. The first theme had four subthemes: (a) brief and flexible structure, (b) online modality, (c) sensitive and positive coach and (d) organisational awareness. The second theme had three subthemes: (a) specific language and behaviour recommendations, (b) adaptable to different service-users and situations and (c) confer relevant emotional skills and techniques. Conclusions: Communication Coaching could be a feasible and acceptable intervention for qualified sonographers if specific, limited adaptations are made as recommended by the stakeholders. Further evaluation of the intervention in practice is necessary

An fMRI Investigation of Preparatory Set in the Human Cerebral Cortex and Superior Colliculus for Pro- and Anti-Saccades

Previous studies have identified several cortical regions that show larger BOLD responses during preparation and execution of anti-saccades than pro-saccades. We confirmed this finding with a greater BOLD response for anti-saccades than pro-saccades during the preparation phase in the FEF, IPS and DLPFC and in the FEF and IPS in the execution phase. We then applied multi-voxel pattern analysis (MVPA) to establish whether different neural populations are involved in the two types of saccade. Pro-saccades and anti-saccades were reliably decoded during saccade execution in all three cortical regions (FEF, DLPFC and IPS) and in IPS during saccade preparation. This indicates neural specialization, for programming the desired response depending on the task rule, in these regions. In a further study tailored for imaging the superior colliculus in the midbrain a similar magnitude BOLD response was observed for pro-saccades and anti-saccades and the two saccade types could not be decoded with MVPA. This was the case both for activity related to the preparation phase and also for that elicited during the execution phase. We conclude that separate cortical neural populations are involved in the task-specific programming of a saccade while in contrast, the SC has a role in response preparation but may be less involved in high-level, task-specific aspects of the control of saccades

Employing the Gini coefficient to measure participation inequality in treatment-focused Digital Health Social Networks

Digital Health Social Networks (DHSNs) are common; however, there are few metrics that can be used to identify participation inequality. The objective of this study was to investigate whether the Gini coefficient, an economic measure of statistical dispersion traditionally used to measure income inequality, could be employed to measure DHSN inequality. Quarterly Gini coefficients were derived from four long-standing DHSNs. The combined data set included 625,736 posts that were generated from 15,181 actors over 18,671 days. The range of actors (8–2323), posts (29–28,684), and Gini coefficients (0.15–0.37) varied. Pearson correlations indicated statistically significant associations between number of actors and number of posts (0.527–0.835, p < .001), and Gini coefficients and number of posts (0.342–0.725, p < .001). However, the association between Gini coefficient and number of actors was only statistically significant for the addiction networks (0.619 and 0.276, p < .036). Linear regression models had positive but mixed R2 results (0.333–0.527). In all four regression models, the association between Gini coefficient and posts was statistically significant (t = 3.346–7.381, p < .002). However, unlike the Pearson correlations, the association between Gini coefficient and number of actors was only statistically significant in the two mental health networks (t = −4.305 and −5.934, p < .000). The Gini coefficient is helpful in measuring shifts in DHSN inequality. However, as a standalone metric, the Gini coefficient does not indicate optimal numbers or ratios of actors to posts, or effective network engagement. Further, mixed-methods research investigating quantitative performance metrics is required

A qualitative evaluation of a novel intervention using insight into tobacco industry tactics to prevent the uptake of smoking in school-aged children

Background: Evidence from the US Truth campaign suggests that interventions focusing on tobacco industry tactics can be effective in preventing smoking uptake by children. Operation Smoke Storm is the first school-based intervention based on this premise and comprises three classroom sessions in which students act as secret agents uncovering tobacco industry tactics through videos, quizzes, discussions, and presentations. We report a qualitative evaluation of its acceptability. Methods: We conducted eight focus groups with 79 students aged 11-12 who participated in Operation Smoke Storm at two UK schools in Autumn 2013, and 20 interviews with teachers who delivered the intervention. These were digitally audio-recorded, transcribed verbatim and analysed using the framework method. Results: Students enjoyed the secret agent scenario and reported acquiring new knowledge about smoking and the tobacco industry, which seemed to strengthen their aversion to smoking. Teachers felt confident delivering the ‘off the shelf’ resource, although they would have welcomed more background information about the topic and guidance on steering discussions. Teachers highlighted a need for the resource to be flexible and not dependent on lesson length, teacher confidence, or expertise. Students and teachers endorsed the idea of developing a booster component for older students and supported the development of printed information complementing the resource to encourage parents to support their child not to smoke. Conclusions: These findings demonstrate that Operation Smoke Storm can be delivered by teachers to raise awareness about smoking-related issues. The ideas and issues raised are now being used to improve and extend the resource for further evaluation

Quality of life and cost-effectiveness of interferon-alpha in malignant melanoma: results from randomised trial

A definitive conclusion regarding the value of low-dose extended duration adjuvant interferon-alpha therapy in the treatment of malignant melanoma is only possible once data on health-related quality of life (HRQoL) and costs have been considered. This trial randomised 674 patients to interferon alpha-2a (3 megaunits three times per week for 2 years or until recurrence) or placebo. Health-related quality of life (QoL) was to be assessed up to 60 months using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. Data for the economic analysis, including cost information and the EQ-5D were also collected. Patients in the observation (OBS) group had significantly better mean follow-up quality of on five dimensions of the EORTC QLQ-C30 functional scales: role functioning (P=0.033), emotional functioning (P=0.003), cognitive functioning (P=0.001), social functioning (P=0.003) and global health status (P=0.001). Patients in the OBS group had significantly better mean follow-up symptom scores on seven dimensions of the EORTC QLQ-C30 V1 symptom scales. Economic data showed that costs were £3066 higher in the interferon group and produces an incremental cost per quality-adjusted life year of £41 432 at 5 years. The results show that interferon has significant effects on QoL and symptomatology and is unlikely to be cost-effective in this patient group in the UK

A Genetic Screen Reveals Arabidopsis Stomatal and/or Apoplastic Defenses against Pseudomonas syringae pv. tomato DC3000

Bacterial infection of plants often begins with colonization of the plant surface, followed by entry into the plant through wounds and natural openings (such as stomata), multiplication in the intercellular space (apoplast) of the infected tissues, and dissemination of bacteria to other plants. Historically, most studies assess bacterial infection based on final outcomes of disease and/or pathogen growth using whole infected tissues; few studies have genetically distinguished the contribution of different host cell types in response to an infection. The phytotoxin coronatine (COR) is produced by several pathovars of Pseudomonas syringae. COR-deficient mutants of P. s. tomato (Pst) DC3000 are severely compromised in virulence, especially when inoculated onto the plant surface. We report here a genetic screen to identify Arabidopsis mutants that could rescue the virulence of COR-deficient mutant bacteria. Among the susceptible to coronatine-deficient Pst DC3000 (scord) mutants were two that were defective in stomatal closure response, two that were defective in apoplast defense, and four that were defective in both stomatal and apoplast defense. Isolation of these three classes of mutants suggests that stomatal and apoplastic defenses are integrated in plants, but are genetically separable, and that COR is important for Pst DC3000 to overcome both stomatal guard cell- and apoplastic mesophyll cell-based defenses. Of the six mutants defective in bacterium-triggered stomatal closure, three are defective in salicylic acid (SA)-induced stomatal closure, but exhibit normal stomatal closure in response to abscisic acid (ABA), and scord7 is compromised in both SA- and ABA-induced stomatal closure. We have cloned SCORD3, which is required for salicylic acid (SA) biosynthesis, and SCORD5, which encodes an ATP-binding cassette (ABC) protein, AtGCN20/AtABCF3, predicted to be involved in stress-associated protein translation control. Identification of SCORD5 begins to implicate an important role of stress-associated protein translation in stomatal guard cell signaling in response to microbe-associated molecular patterns and bacterial infection

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Visually Driven Activation in Macaque Areas V2 and V3 without Input from the Primary Visual Cortex

Creating focal lesions in primary visual cortex (V1) provides an opportunity to study the role of extra-geniculo-striate pathways for activating extrastriate visual cortex. Previous studies have shown that more than 95% of neurons in macaque area V2 and V3 stop firing after reversibly cooling V1 [1], [2], [3]. However, no studies on long term recovery in areas V2, V3 following permanent V1 lesions have been reported in the macaque. Here we use macaque fMRI to study area V2, V3 activity patterns from 1 to 22 months after lesioning area V1. We find that visually driven BOLD responses persist inside the V1-lesion projection zones (LPZ) of areas V2 and V3, but are reduced in strength by ∼70%, on average, compared to pre-lesion levels. Monitoring the LPZ activity over time starting one month following the V1 lesion did not reveal systematic changes in BOLD signal amplitude. Surprisingly, the retinotopic organization inside the LPZ of areas V2, V3 remained similar to that of the non-lesioned hemisphere, suggesting that LPZ activation in V2, V3 is not the result of input arising from nearby (non-lesioned) V1 cortex. Electrophysiology recordings of multi-unit activity corroborated the BOLD observations: visually driven multi-unit responses could be elicited inside the V2 LPZ, even when the visual stimulus was entirely contained within the scotoma induced by the V1 lesion. Restricting the stimulus to the intact visual hemi-field produced no significant BOLD modulation inside the V2, V3 LPZs. We conclude that the observed activity patterns are largely mediated by parallel, V1-bypassing, subcortical pathways that can activate areas V2 and V3 in the absence of V1 input. Such pathways may contribute to the behavioral phenomenon of blindsight