Neural regulation of cancer: from mechanobiology to inflammation.

Despite recent progress in cancer research, the exact nature of malignant transformation and its progression is still not fully understood. Particularly metastasis, which accounts for most cancer death, is a very complex process, and new treatment strategies require a more comprehensive understanding of underlying regulatory mechanisms. Recently, the sympathetic nervous system (SNS) has been implicated in cancer progression and beta-blockers have been identified as a novel strategy to limit metastasis. This review discusses evidence that SNS signaling regulates metastasis by modulating the physical characteristics of tumor cells, tumor-associated immune cells and the extracellular matrix (ECM). Altered mechanotype is an emerging hallmark of cancer cells that is linked to invasive phenotype and treatment resistance. Mechanotype also influences crosstalk between tumor cells and their environment, and may thus have a critical role in cancer progression. First, we discuss how neural signaling regulates metastasis and how SNS signaling regulates both biochemical and mechanical properties of tumor cells, immune cells and the ECM. We then review our current knowledge of the mechanobiology of cancer with a focus on metastasis. Next, we discuss links between SNS activity and tumor-associated inflammation, the mechanical properties of immune cells, and how the physical properties of the ECM regulate cancer and metastasis. Finally, we discuss the potential for clinical translation of our knowledge of cancer mechanobiology to improve diagnosis and treatment

Characterization of Epoxy/Amine Networks with Glycidal Polyhedral Oligomeric Silsesquioxane Surface Modified Silica Nanoparticles

Silica nanoparticles were surface modified with octa-functional glycidal polyhedral oligomeric silsesquioxane (G-POSS) and incorporated into an epoxy/amine system in an effort to increase the mechanical performance of the inorganic/organic hybrid material. The silica nanoparticles were first functionalized with 3-aminoprpyltrimethoxysilane (APTMOS) at 5 and 10 weight percent, and then modified with G-POSS at ratios of 1:10 and 1:5 (APTMOS: G-POSS). The modified particles were then incorporated into an epoxy/amine network consisting of diglycidyl ether of bisphenol A (DGEBA) and aromatic amine, diamine diphenyl sulfone (4,4’ DDS) at 1 and 5 weight percent, resulting in 8 different formulations. The incorporation of the modified silica nanoparticles caused changes in crosslink density depending on the amount functionalization density, G-POSS modification, and loading. Samples with nanoparticles of higher functionalization density and lower G-POSS modification exhibited higher crosslink density due to high functionalization and lower free volume. It was determined that incorporation of inorganic POSS cage disrupted network formation and chain packing. Similar trends follow suite with the strength of the material in compressive analysis. The incorporation of the nanoparticles slightly decreased the gel point of the material as compared to that of the control. Furthermore, it was determined that there is an optimum degree of modification and loading that would influence the mechanical properties and performance of the material to its optimal values

Managing the Central Artery/Tunnel Project: An Exploration of Potential Cost Savings

The John W. McCormack Institute of Public Affairs at the University of Massachusetts Boston is an institution whose primary mission is public service. Through public policy research, educational programs, policy practice and the dissemination ofknowledge, the Institute seeks to have a constructive impact on policy formulation, problem solving and public discourse concerning urgent civic challenges facing state and local government in the New England region. In 1996, under Chapter 205 of the 1996 Acts and Resolves, the Massachusetts legislature authorized the Institute to undertake a study *to review and explore possible cost savings within the Central Artery/Third Harbor Tunnel project and report its findings to the House and Senate Committees on Ways and Means and the Joint Committee on Transportation. In devising the scope of study, our focus has been on analyzing costs of the project through the prism of good public policy — that is, to identify the interests of the Commonwealth, as the ultimate owner of the project, in its size and scope, current status, and expected outcomes. Our team consisted of experienced public policy analysts recruited from within the ranks ofthe Institute and outside. It included experts on engineering and construction industry practices in the Commonwealth, but with no past or current involvement in the CA/T program. With this focus and objective, we did not play the role of a financial auditor or an evaluator of the engineering designs. We did not play the role of an in-depth evaluator ofmanagement practices as would an outside management expert. Nor did we attempt to duplicate the legally mandated reviews of the numerous federal and state agencies with continuing responsibly for project oversight. Our role, then, has been that of a neutral broker. The starting point for this review was the cost estimates contained in the Massachusetts Highway Department Finance Plan for the Central Artery/Tunnel Project, dated September 30, 1996, which estimated the overall cost of the project at $10.4+ billion when completed.$4.9 billion has been spent as of June 30, 1996

Abnormalities of the ventilatory equivalent for carbon dioxide in patients with chronic heart failure

Introduction. The relation between minute ventilation (VE) and carbon dioxide production (VCO2) can be characterised by the instantaneous ratio of ventilation to carbon dioxide production, the ventilatory equivalent for CO2 (VEqCO2). We hypothesised that the time taken to achieve the lowest VEqCO2 (time to VEqCO2 nadir) may be a prognostic marker in patients with chronic heart failure (CHF). Methods. Patients and healthy controls underwent a symptom-limited, cardiopulmonary exercise test (CPET) on a treadmill to volitional exhaustion. Results. 423 patients with CHF (mean age 63±12 years; 80% males) and 78 healthy controls (62% males; age 61±11 years) were recruited. Time to VEqCO2 nadir was shorter in patients than controls (327±204 s versus 514±187 s; P=0.0001). Univariable predictors of all-cause mortality included peak oxygen uptake (X 2 =53.0), VEqCO2 nadir (X 2 =47.9), and time to VEqCO2 nadir (X 2 =24.0). In an adjusted Cox multivariable proportional hazards model, peak oxygen uptake (X 2 =16.7) and VEqCO2 nadir (X 2 =17.9) were the most significant independent predictors of all-cause mortality. Conclusion. The time to VEqCO2 nadir was shorter in patients with CHF than in normal subjects and was a predictor of subsequent mortality. © 2012 Lee Ingle et al

Measuring Bonds in Equine-Facilitated Psychotherapy

Equine-facilitated psychotherapy is a type of animal-assisted intervention that has potential to be an effective therapeutic modality in the treatment of psychiatric disorders. It is theorized that a meaningful relationship is formed between client and horse; this relationship is thought to inspire meaningful change in the client. The current study found evidence of human-equine bonds and determined they can be measured quantitatively using adapted bonding scales. This study also explored variables that may impact bonds formed between clients and horse co-therapists. Finally, a potential correlation between the strength of the bond and the severity of symptoms over the course of therapy was investigated

Enlightenment Architectures and the reconstruction of Sir Hans Sloane's Cabinets of Miscellanies

Focusing on Sir Hans Sloane’s catalogue of ‘Miscellanies’, now in the British Museum, this paper asks firstly how Sloane described objects and secondly whether the original contents of the cabinets can be reconstructed from his catalogue. Drawing on a sustained, digitally augmented analysis – the first of its kind – of Sloane’s catalogues, we respond to these questions and offer an initial analysis of the contents of the cabinets that held the miscellaneous objects at Sloane’s manor house in Chelsea. Knowledge of how and why Sloane catalogued this part of his collection has hitherto remained underdeveloped. We argue that his focus on preservation and documentation in his cataloguing did not preclude a research role, but rather was founded on immersive participation. Our work was undertaken as part of a Leverhulme Trust funded research project, Enlightenment Architectures: Sir Hans Sloane’s Catalogues of his Collections (2016–19), a collaboration between the British Museum and University College London