Reduction of Murine Cutaneous UVB-Induced Tumor-Infiltrating T Lymphocytes by Dietary Canthaxanthin

The effect of dietary canthaxanthin, retinyl palmitate, or their combination on the tumor-infiltrating T-lymphocyte response (T-TIL) in de novo murine ultraviolet type B irradiation-induced tumors was investigated to elucidate potential mechanisms of action of these compounds. We found that dietary canthaxanthin greatly reduced the number of tumor-infiltrating helper/inducer, suppressor/cytotoxic, and interleukin-2 receptor-positive T lymphocytes and also observed a concomitant statistically significant increase in tumour incidence in canthaxanthin-fed animals. The addition of retinyl palmitate to the canthaxanthin diet ameliorated this negative effect on TIL and the development of skin tumors. We conclude that dietary retinyl palmitate and canthaxanthin can modulate the host T-cell immune response within a growing tumor and may affect tumorigenicity

Abnormal morphology biases haematocrit distribution in tumour vasculature and contributes to heterogeneity in tissue oxygenation

Oxygen heterogeneity in solid tumors is recognized as a limiting factor for therapeutic efficacy. This heterogeneity arises from the abnormal vascular structure of the tumor, but the precise mechanisms linking abnormal structure and compromised oxygen transport are only partially understood. In this paper, we investigate the role that red blood cell (RBC) transport plays in establishing oxygen heterogeneity in tumor tissue. We focus on heterogeneity driven by network effects, which are challenging to observe experimentally due to the reduced fields of view typically considered. Motivated by our findings of abnormal vascular patterns linked to deviations from current RBC transport theory, we calculated average vessel lengths L⎯⎯ and diameters d⎯⎯ from tumor allografts of three cancer cell lines and observed a substantial reduction in the ratio λ=L⎯⎯/d⎯⎯ compared to physiological conditions. Mathematical modeling reveals that small values of the ratio λ (i.e., λ<6 ) can bias hematocrit distribution in tumor vascular networks and drive heterogeneous oxygenation of tumor tissue. Finally, we show an increase in the value of λ in tumor vascular networks following treatment with the antiangiogenic cancer agent DC101. Based on our findings, we propose λ as an effective way of monitoring the efficacy of antiangiogenic agents and as a proxy measure of perfusion and oxygenation in tumor tissue undergoing antiangiogenic treatment

The Importance of Tree Size and Fecundity for Wind Dispersal of Big-Leaf Mahogany

Seed dispersal by wind is a critical yet poorly understood process in tropical forest trees. How tree size and fecundity affect this process at the population level remains largely unknown because of insufficient replication across adults. We measured seed dispersal by the endangered neotropical timber species big-leaf mahogany (Swietenia macrophylla King, Meliaceae) in the Brazilian Amazon at 25 relatively isolated trees using multiple 1-m wide belt transects extended 100 m downwind. Tree diameter and fecundity correlated positively with increased seed shadow extent; but in combination large, high fecundity trees contributed disproportionately to longer-distance dispersal events (>60 m). Among three empirical models fitted to seed density vs. distance in one dimension, the Student-t (2Dt) generally fit best (compared to the negative exponential and inverse power). When seedfall downwind was modelled in two dimensions using a normalised sample, it peaked furthest downwind (c. 25 m) for large, high-fecundity trees; with the inverse Gaussian and Weibull functions providing comparable fits that were slightly better than the lognormal. Although most seeds fell within 30 m of parent trees, relatively few juveniles were found within this distance, resulting in juvenile-to-seed ratios peaking at c. 35–45 m. Using the 2Dt model fits to predict seed densities downwind, coupled with known fecundity data for 2000–2009, we evaluated potential Swietenia regeneration near adults (≤30 m dispersal) and beyond 30 m. Mean seed arrival into canopy gaps >30 m downwind was more than 3× greater for large, high fecundity trees than small, high-fecundity trees. Tree seed production did not necessarily scale up proportionately with diameter, and was not consistent across years, and this resulting intraspecific variation can have important consequences for local patterns of dispersal in forests. Our results have important implications for management and conservation of big-leaf mahogany populations, and may apply to other threatened wind-dispersed Meliaceae trees

Lessons from using iPads to understand young children's creativity

This paper explores how iPads can be used as part of a child-centred data collection approach to understanding young children’s creativity. Evidence is presented from a pilot study about 3- to 5-year-old children’s creative play. Researchers’ reflective accounts of children’s engagement with iPad video diaries and free to use apps were logged across two early educational settings over a three-month period. Findings suggest that iPads offer a mechanism to allow children to express their creative play and to encourage involvement in the research process. However, bespoke research software to use with early years children is required to improve this process

Dissociable effects of APOE ε4 and β-amyloid pathology on visual working memory

Although APOE ε4 carriers are at substantially higher risk of developing Alzheimer’s disease than noncarriers, controversial evidence suggests that APOE ε4 might confer some advantages, explaining the survival of this gene (antagonistic pleiotropy). In a population-based cohort born in one week in 1946 (assessed aged 69–71 years), we assessed differential effects of APOE ε4 and β-amyloid pathology (quantified using 18F-Florbetapir-PET) on visual working memory (object–location binding). In 398 cognitively normal participants, APOE ε4 and β-amyloid had opposing effects on object identification, predicting better and poorer recall, respectively. ε4 carriers also recalled locations more precisely, with a greater advantage at higher β-amyloid burden. These results provide evidence of superior visual working memory in ε4 carriers, showing that some benefits of this genotype are demonstrable in older age, even in the preclinical stages of Alzheimer’s disease

Primary Hyperparathyroidism Patients with Positive Preoperative Sestamibi Scan and Negative Ultrasound Are More Likely to Have Posteriorly Located Upper Gland Adenomas (PLUGs)

BackgroundStandard preoperative imaging for primary hyperparathyroidism usually includes sestamibi scanning (MIBI) and ultrasound (US). In a subset of patients with a positive MIBI and a negative US, we hypothesize that the parathyroid adenomas are more likely to be located posteriorly in the neck, where anatomically they are more difficult to detect by US.MethodsWe retrospectively reviewed the records of 661 patients treated for primary hyperparathyroidism between 2004 and 2009 at a tertiary referral center. We included patients who for their first operation had a MIBI that localized a single lesion in the neck and an US that found no parathyroid adenoma. We excluded patients with persistent or recurrent hyperparathyroidism, and patients with MIBIs that were negative, that had more than one positive focus, or that had foci outside of the neck. Sixty-six cases were included in the final analysis.ResultsA total of 54 patients (83%) had a single adenoma, 4 (6%) had double adenomas, and 7 (11%) had hyperplasia. Thirty-three patients (51%) had a single upper gland adenoma; 19 of these (58%) were posteriorly located upper gland adenomas (PLUGs). PLUGs occurred more often on the right side than on the left (P = 0.048, Fisher's test). PLUGs were also larger than other single adenomas (mean 1.85 vs. 1.48 cm, P = 0.021, t-test). Seventy-six percent of patients successfully underwent a unilateral or focused exploration. Six patients (9%) had persistent disease, which is double our group's overall average (4-5%).ConclusionsPrimary hyperparathyroid patients with preoperative positive MIBI and negative US are more likely to have PLUGs

Chaste : Cancer, Heart and Soft Tissue Environment

Funding: UK Engineering and Physical Sciences Research Council [grant number EP/N509711/1 (J.K.)].Chaste (Cancer, Heart And Soft Tissue Environment) is an open source simulation package for the numerical solution of mathematical models arising in physiology and biology. To date, Chaste development has been driven primarily by applications that include continuum modelling of cardiac electrophysiology (‘Cardiac Chaste’), discrete cell-based modelling of soft tissues (‘Cell-based Chaste’), and modelling of ventilation in lungs (‘Lung Chaste’). Cardiac Chaste addresses the need for a high-performance, generic, and verified simulation framewor kfor cardiac electrophysiology that is freely available to the scientific community. Cardiac chaste provides a software package capable of realistic heart simulations that is efficient, rigorously tested, and runs on HPC platforms. Cell-based Chaste addresses the need for efficient and verified implementations of cell-based modelling frameworks, providing a set of extensible tools for simulating biological tissues. Computational modelling, along with live imaging techniques, plays an important role in understanding the processes of tissue growth and repair. A wide range of cell-based modelling frameworks have been developed that have each been successfully applied in a range of biological applications. Cell-based Chaste includes implementations of the cellular automaton model, the cellular Potts model, cell-centre models with cell representations as overlapping spheres or Voronoi tessellations, and the vertex model. Lung Chaste addresses the need for a novel, generic and efficient lung modelling software package that is both tested and verified. It aims to couple biophysically-detailed models of airway mechanics with organ-scale ventilation models in a package that is freely available to the scientific community.Publisher PDFPeer reviewe

Island Invasion by a Threatened Tree Species: Evidence for Natural Enemy Release of Mahogany (Swietenia macrophylla) on Dominica, Lesser Antilles

Despite its appeal to explain plant invasions, the enemy release hypothesis (ERH) remains largely unexplored for tropical forest trees. Even scarcer are ERH studies conducted on the same host species at both the community and biogeographical scale, irrespective of the system or plant life form. In Cabrits National Park, Dominica, we observed patterns consistent with enemy release of two introduced, congeneric mahogany species, Swietenia macrophylla and S. mahagoni, planted almost 50 years ago. Swietenia populations at Cabrits have reproduced, with S. macrophylla juveniles established in and out of plantation areas at densities much higher than observed in its native range. Swietenia macrophylla juveniles also experienced significantly lower leaf-level herbivory (∼3.0%) than nine co-occurring species native to Dominica (8.4–21.8%), and far lower than conspecific herbivory observed in its native range (11%–43%, on average). These complimentary findings at multiple scales support ERH, and confirm that Swietenia has naturalized at Cabrits. However, Swietenia abundance was positively correlated with native plant diversity at the seedling stage, and only marginally negatively correlated with native plant abundance for stems ≥1-cm dbh. Taken together, these descriptive patterns point to relaxed enemy pressure from specialized enemies, specifically the defoliator Steniscadia poliophaea and the shoot-borer Hypsipyla grandella, as a leading explanation for the enhanced recruitment of Swietenia trees documented at Cabrits

Hidden, visceral and traumatic: a dramaturgical approach to men talking about their penis after surgery for penile cancer

YesDrawing upon concepts of expressive equipment and body image, the aim of this study is to explore how men diagnosed and treated for penile cancer construct their penis and its surgical disfigurement (penectomy). Using maximum variation sampling with the intention to acquire the broadest range of experiences of stage of disease and treatment, 27 cisgender men (aged 48-83, x=63) who had surgical treatment consented for their data to be archived for analysis. From a dramaturgical perspective, the constructionist thematic analysis explored direct and indirect talk about the penis after surgery. The analysis showed that through graphic and sequential narratives of dismemberment revealed, participants constructed a post-surgery period in which they both wanted and did-not-want to see their penis. Additionally, participants constructed themselves managing difficult emotions through others and seeing themselves being rejected by a potentially desiring (female) Other. The findings extend research on male genitals by showing how the post-surgery penis can function as something hidden but visceral and traumatic when revealed. Importantly, this paper illustrates body image as expressive equipment where body and identity are formed in the image of manhood, which is an intersubjective (sexual) object between self and other.This paper presents independent research commissioned by the National Institute for Health Research (NIHR) under its Research for Patient Benefit (RfPB) Programme (Grant Reference Number PB-PG-0808-17158).Research Development Fund Publication Prize Award winner, October 2019