Emerging aspects of oesophageal and gastro-oesophageal junction cancer histopathology – an update for the surgical oncologist

Adenocarcinoma of the oesophagus and gastro-oesophageal junction are rapidly increasing in incidence and have a well described sequence of carcinogenesis: the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. During recent years there have been changes in the knowledge surrounding disease progression, cancer management and histopathology specimen reporting. Tumours around the gastro-oesophageal junction (GOJ) pose several specific challenges. Numerous difficulties arise when the existing TNM staging systems for gastric and oesophageal cancers are applied to GOJ tumours. The issues facing the current TNM staging and GOJ tumour classification systems are reviewed in this article. Recent evidence regarding the importance of several histopathologically derived prognostic factors, such as circumferential resection margin status and lymph node metastases, have implications for specimen reporting. With the rising use of multimodal treatments for oesophageal cancer it is important that the response of the tumour to this therapy is carefully documented pathologically. In addition, several controversial and novel areas such as endoscopic mucosal resection, lymph node micrometastases and the sentinel node concept are being studied. We aim to review these aspects, with special relevance to oesophageal and gastro-oesophageal cancer specimen reporting, to update the surgical oncologist with an interest in upper gastrointestinal cancer

Designing 3-D prints for blind and partially sighted audiences in museums : exploring the needs of those living with sight loss

Modern museum practice embraces equal access for all, but access for blind and partially-sighted (BPS) audience remains problematic given the ocularcentricity of museums. Many museum professionals and BPS visitors remain frustrated by the degree of accessibility on offer. The use of 3-D printed replicas as a handling surrogate represents a solution, allowing BPS visitors to engage tactually with museum content while minimizing risk. However, the design of such replicas is poorly researched. This exploratory examination of the design of 3-D printed replicas utilizes semi-structured interviews, sensory observations and content analysis to examine BPS perceptions of museum objects in the absence of interpretational support. Interpretation was dominantly multisensory, while participants found it easier to determine material traits than object traits, with textual, geometrical and optical properties being of use. Assistive approaches rather than major alterations were favored. Overall, museum professionals should consider how the process of 3-D printing influences BPS perception

New frontiers in belowground ecology for plant protection from root-feeding insects

Herbivorous insect pests living in the soil represent a significant challenge to food security given their persistence, the acute damage they cause to plants and the difficulties associated with managing their populations. Ecological research effort into rhizosphere interactions has increased dramatically in the last decade and we are beginning to understand, in particular, the ecology of how plants defend themselves against soil-dwelling pests. In this review, we synthesise information about four key ecological mechanisms occurring in the rhizosphere or surrounding soil that confer plant protection against root herbivores. We focus on root tolerance, root resistance via direct physical and chemical defences, particularly via acquisition of silicon-based plant defences, integration of plant mutualists (microbes and entomopathogenic nematodes, EPNs) and the influence of soil history and feedbacks. Their suitability as management tools, current limitations for their application, and the opportunities for development are evaluated. We identify opportunities for synergy between these aspects of rhizosphere ecology, such as mycorrhizal fungi negatively affecting pests at the root-interface but also increasing plant uptake of silicon, which is also known to reduce herbivory. Finally, we set out research priorities for developing potential novel management strategies

Visually assessed breast density, breast cancer risk and the importance of the craniocaudal view

Contains fulltext : 69403.pdf (publisher's version ) (Open Access)INTRODUCTION: Mammographic density is known to be a strong risk factor for breast cancer. A particularly strong association with risk has been observed when density is measured using interactive threshold software. This, however, is a labour-intensive process for large-scale studies. METHODS: Our aim was to determine the performance of visually assessed percent breast density as an indicator of breast cancer risk. We compared the effect on risk of density as measured with the mediolateral oblique view only versus that estimated as the average density from the mediolateral oblique view and the craniocaudal view. Density was assessed using a visual analogue scale in 10,048 screening mammograms, including 311 breast cancer cases diagnosed at that screening episode or within the following 6 years. RESULTS: Where only the mediolateral oblique view was available, there was a modest effect of breast density on risk with an odds ratio for the 76% to 100% density relative to 0% to 25% of 1.51 (95% confidence interval 0.71 to 3.18). When two views were available, there was a considerably stronger association, with the corresponding odds ratio being 6.77 (95% confidence interval 2.75 to 16.67). CONCLUSION: This indicates that a substantial amount of information on risk from percentage breast density is contained in the second view. It also suggests that visually assessed breast density has predictive potential for breast cancer risk comparable to that of density measured using the interactive threshold software when two views are available. This observation needs to be confirmed by studies applying the different measurement methods to the same individuals

Microbiome and infectivity studies reveal complex polyspecies tree disease in Acute Oak Decline

Decline-diseases are complex and becoming increasingly problematic to tree health globally. Acute Oak Decline (AOD) is characterized by necrotic stem lesions and galleries of the bark-boring beetle, Agrilus biguttatus, and represents a serious threat to oak. Although multiple novel bacterial species and Agrilus galleries are associated with AOD lesions, the causative agent(s) are unknown. The AOD pathosystem therefore provides an ideal model for a systems-based research approach to address our hypothesis that AOD lesions are caused by a polymicrobial complex. Here we show that three bacterial species, Brenneria goodwinii, Gibbsiella quercinecans and Rahnella victoriana, are consistently abundant in the lesion microbiome and possess virulence genes used by canonical phytopathogens that are expressed in AOD lesions. Individual and polyspecies inoculations on oak logs and trees demonstrated that B. goodwinii and G. quercinecans cause tissue necrosis and, in combination with A. biguttatus, produce the diagnostic symptoms of AOD. We have proved a polybacterial cause of AOD lesions, providing new insights into polymicrobial interactions and tree disease. This work presents a novel conceptual and methodological template for adapting Koch’s postulates to address the role of microbial communities in disease

A new method for spatially resolving the turbulence driving mixture in the ISM with application to the Small Magellanic Cloud

Turbulence plays a crucial role in shaping the structure of the interstellar medium. The ratio of the three-dimensional density contrast ($\sigma_{\rho/\rho_0}$) to the turbulent sonic Mach number ($\mathcal{M}$) of an isothermal, compressible gas describes the ratio of solenoidal to compressive modes in the turbulent acceleration field of the gas, and is parameterised by the turbulence driving parameter: $b=\sigma_{\rho/\rho_0}/\mathcal{M}$. The turbulence driving parameter ranges from $b=1/3$ (purely solenoidal) to $b=1$ (purely compressive), with $b=0.38$ characterising the natural mixture (1/3~compressive, 2/3~solenoidal) of the two driving modes. Here we present a new method for recovering $\sigma_{\rho/\rho_0}$, $\mathcal{M}$, and $b$, from observations on galactic scales, using a roving kernel to produce maps of these quantities from column density and centroid velocity maps. We apply our method to high-resolution HI emission observations of the Small Magellanic Cloud (SMC) from the GASKAP-HI survey. We find that the turbulence driving parameter varies between $b\sim 0.3$ and $b\sim 1.0$ within the main body of the SMC, but the median value converges to $b\sim0.51$, suggesting that the turbulence is overall driven more compressively ($b>0.38$). We observe no correlation between the $b$ parameter and HI or H$\alpha$ intensity, indicating that compressive driving of HI turbulence cannot be determined solely by observing HI or H$\alpha$ emission density, and that velocity information must also be considered. Further investigation is required to link our findings to potential driving mechanisms such as star-formation feedback, gravitational collapse, or cloud-cloud collisions.Comment: 20 pages, 16 figures, accepted to MNRA

Quantitative and textural analysis of magnetization transfer and diffusion images in the early detection of brain metastases.

PURPOSE: The sensitivity of the magnetization transfer ratio (MTR) and apparent diffusion coefficient (ADC) for early detection of brain metastases was investigated in mice and humans. METHODS: Mice underwent MRI twice weekly for up to 31 d following intracardiac injection of the brain-homing breast cancer cell line MDA-MB231-BR. Patients with small cell lung cancer underwent quarterly MRI for 1 year. MTR and ADC were measured in regions of metastasis and matched contralateral tissue at the final time point and in registered regions at earlier time points. Texture analysis and linear discriminant analysis were performed to detect metastasis-containing slices. RESULTS: Compared with contralateral tissue, mouse metastases had significantly lower MTR and higher ADC at the final time point. Some lesions were visible at earlier time points on the MTR and ADC maps: 24% of these were not visible on corresponding T2 -weighted images. Texture analysis using the MTR maps showed 100% specificity and 98% sensitivity for metastasis at the final time point, with 77% sensitivity 2-4 d earlier and 46% 5-8 d earlier. Only 2 of 16 patients developed metastases, and their penultimate scans were normal. CONCLUSIONS: Some brain metastases may be detected earlier on MTR than conventional T2 ; however, the small gain is unlikely to justify "predictive" MRI. Magn Reson Med 77:1987-1995, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.The authors gratefully acknowledge the Cambridge Institute Biological Resources Unit for expert animal care and technical assistance, the Histopathology Core Facility, Drs Joe Frank and Diane Palmieri for providing the cell line, the advice of Dr. Dan Tozer, and the support of Cancer Research UK [grant number C14303/A17197], the Brian Cross Memorial Trust, the Addenbrooke’s Charitable Trust, the University of Cambridge, Hutchison Whampoa Ltd, the Cambridge Experimental Cancer Medicine Centre, and the NIHR Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from Wiley via https://doi.org/10.1002/mrm.2625

Rituximab in B-Cell Hematologic Malignancies: A Review of 20 Years of Clinical Experience

Rituximab is a human/murine, chimeric anti-CD20 monoclonal antibody with established efficacy, and a favorable and well-defined safety profile in patients with various CD20-expressing lymphoid malignancies, including indolent and aggressive forms of B-cell non-Hodgkin lymphoma. Since its first approval 20 years ago, intravenously administered rituximab has revolutionized the treatment of B-cell malignancies and has become a standard component of care for follicular lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia, and mantle cell lymphoma. For all of these diseases, clinical trials have demonstrated that rituximab not only prolongs the time to disease progression but also extends overall survival. Efficacy benefits have also been shown in patients with marginal zone lymphoma and in more aggressive diseases such as Burkitt lymphoma. Although the proven clinical efficacy and success of rituximab has led to the development of other anti-CD20 monoclonal antibodies in recent years (e.g., obinutuzumab, ofatumumab, veltuzumab, and ocrelizumab), rituximab is likely to maintain a position within the therapeutic armamentarium because it is well established with a long history of successful clinical use. Furthermore, a subcutaneous formulation of the drug has been approved both in the EU and in the USA for the treatment of B-cell malignancies. Using the wealth of data published on rituximab during the last two decades, we review the preclinical development of rituximab and the clinical experience gained in the treatment of hematologic B-cell malignancies, with a focus on the well-established intravenous route of administration. This article is a companion paper to A. Davies, et al., which is also published in this issue