Patrick Curry interview with Tom Shippey

Patrick Curry interview with Tom Shippey in November 201

Taking Free Flap Surgery Abroad: A Collaborative Approach to a Complex Surgical Problem.

Accessibility to health care, especially complex surgical care, represents one of the major health care disparities in developing countries. While surgical teams may be willing to travel to these areas to help address these needs, there are many logistical and ethical dilemmas inherent in this pursuit. We reviewed our approach to the establishment of the team-based surgical outreach program, wherein we perform head and neck free tissue transfer surgery in Haiti. We describe the challenges encountered in the delivery of surgical care as well as ethical dilemmas relevant to surgical outreach trips, highlighting an approach reliant on strong local cooperation. Despite the obstacles in place, our experience shows that free flap surgery can be successfully and ethically performed in these areas of great need

The flow of colloidal suspensions through porous media

The information in this bulletin was condensed from a dissertation submitted by the senior author to the Graduate Faculty of the University of Missouri in partial fulfillment of the requirements for the degree of Doctor of Philosophy--P. [2].Digitized 2007 AES.Includes bibliographical references (pages 31-32)

Less Noise and More Green : Tolkien\u27s Ideology for England

This essay explores Tolkien’s work (especially The Lord of the Rings) in terms of what I identify as his three central concerns, described here as English culture, nature and ethics. I also defend the work against its detractors, especially cultural materialists. I am more concerned with the reception of the work (e.g. its contemporary meanings) than its production

TP53-inducible Glycolysis and Apoptosis Regulator (TIGAR) Metabolically Reprograms Carcinoma and Stromal Cells in Breast Cancer.

A subgroup of breast cancers has several metabolic compartments. The mechanisms by which metabolic compartmentalization develop in tumors are poorly characterized. TP53 inducible glycolysis and apoptosis regulator (TIGAR) is a bisphosphatase that reduces glycolysis and is highly expressed in carcinoma cells in the majority of human breast cancers. Hence we set out to determine the effects of TIGAR expression on breast carcinoma and fibroblast glycolytic phenotype and tumor growth. The overexpression of this bisphosphatase in carcinoma cells induces expression of enzymes and transporters involved in the catabolism of lactate and glutamine. Carcinoma cells overexpressing TIGAR have higher oxygen consumption rates and ATP levels when exposed to glutamine, lactate, or the combination of glutamine and lactate. Coculture of TIGAR overexpressing carcinoma cells and fibroblasts compared with control cocultures induce more pronounced glycolytic differences between carcinoma and fibroblast cells. Carcinoma cells overexpressing TIGAR have reduced glucose uptake and lactate production. Conversely, fibroblasts in coculture with TIGAR overexpressing carcinoma cells induce HIF (hypoxia-inducible factor) activation with increased glucose uptake, increased 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3), and lactate dehydrogenase-A expression. We also studied the effect of this enzyme on tumor growth. TIGAR overexpression in carcinoma cells increases tumor growth in vivo with increased proliferation rates. However, a catalytically inactive variant of TIGAR did not induce tumor growth. Therefore, TIGAR expression in breast carcinoma cells promotes metabolic compartmentalization and tumor growth with a mitochondrial metabolic phenotype with lactate and glutamine catabolism. Targeting TIGAR warrants consideration as a potential therapy for breast cancer

Tumor Metabolism in the Microenvironment of Nodal Metastasis in Head and Neck Squamous Cell Carcinoma

ABSTRACT Introduction: Monocarboxylate transporter 4 (MCT4) is a cell membrane transporter of lactate. MCT4 is a tumor-specific marker of oxidative stress, glycolysis and hypoxia in tumor stromal cells. We investigated HPV positive and negative tumors with regional metastases to cervical lymph nodes (LN) to study how the metastatic tumor cells interact with their microenvironment. By selecting cancers with extracapsular extension (ECE), we intended to evaluate the interaction between metastases and the surrounding extranodal tissue. Methods: Clinical data were collected from 24 advanced stage oropharyngeal squamous cell carcinoma (OPSCC) patients with neck LN metastasis. All patients presented with at least N1 disease and had ECE. Sixteen cases were negative for HPV and eight were positive. Ten patients (42%) had ECE \u3c 1 mm, and 14 (58%) had ECE \u3e than 1 mm. The extent of ECE was quantified on H&E stains by distance from the edge of capsule. The paraffin-embedded metastatic LN sections were stained with MCT4 and quantification was accomplished using the Aperio Co-localization algorithm. Results: High stromal MCT4 expression was strongly associated with the extent of ECE regardless of HPV status (p=0.031). The stromal MCT4 expression in ECE area was significantly higher as opposed to the surrounding extranodal tissue adjacent to intact capsule (p\u3c0.001). We also found a borderline difference in expression of MCT4 in HPV- LN with ECE \u3e1mm vs. \u3c1mm(p=0.06). Conclusions: MCT4 is a marker of oxidative stress and higher expression of stromal MCT4 in ECE area is significantly correlated with the extent of ECE. The stromal cells separating nests of cancer cells in ECE area have apparent expression of the MCT4. Together these findings provide new insight into the critical role of stromal MCT4 in nodal metastasis and ECE in OPSCC and it may be useful to develop a novel prognostic marker and new anti-cancer agents

Stromal Monocarboxylate Transporter MCT4 is a Poor Prognostic Factor in Squamous Cell Carcinoma

ABSTRACT Introduction: Monocarboxylate transporter 4 (MCT4) is the main exporter of lactate out of cells. It is also a critical component in the glycolytic metabolism of cancer cells. In this study, stromal MCT4 in oral SCC was correlated with risk of recurrence (ROR), extent of primary tumor (pT) and nodal metastasis (pN), perineural invasion (PNI), lymphovascular invasion (LVI), HPV status, extracapsular extension (ECE) and positive margin. Methods: Clinical data were collected for 86 consecutive patients with oral HNSCC. Tissue microarrays (TMA) were constructed from paraffin blocks of resection specimens and stained for MCT4. Immunohistochemistry (IHC) staining was assessed and quantified by digital image analysis with Aperio software. Using a co-localization algorithm we assessed the intensity of staining and the percentage of positive cells in the tumoral stromal cells. Correlations of MCT4 expression with clinicopathological features and survival were studied. Results: Increased IHC staining for MCT4 was strongly associated with an increased risk of recurrence, OR 1.96 (95%CI: 1.17-3.40), presence of PNI, OR 2.25 (95%CI: 1.33-3.95), higher pT, OR 1.68 (95%CI: 0.99-2.89), higher pN, OR 2.07 (95%CI: 1.25-3.57) and presence of LVI, OR 2.21 (95%CI: 1.11-4.67). We didn’t find any significant association between stromal MCT4 expression and HPV status, presence of ECE or positive margin. Conclusions: This study demonstrates that MCT4, a marker of glycolysis in cancer-associated stroma, is highly expressed in oral SCC. The IHC staining pattern of stromal MCT4 suggests that high MCT4 expression appears to be a useful marker for tumor progression and prognosis. We propose MCT4 serves as a new prognostic factor in oral SCC and can act as a potential therapeutic target marker considering pharmacological development of MCT4 inhibitors

Pension Confusion, Uncertainty and Trust in Scotland: An Empirical Analysis

In the context of the new automatic enrolment requirements for all eligible employees to make pension provision for their employees, and the importance of trust in pension provision, this article utilises data from the Scottish Social Attitudes Survey, which, in its 2005 wave, asked correspondents specific questions regarding pension provision. We integrate two different empirical approaches in order to achieve a more robust understanding of pension confusion in Scotland. We find that pension confusion is dominated by pension uncertainty and myopia, but these may be reduced for those working in the financial sector. We consider the implications of these findings for the relationship of trust between employers and their employees, as well as for trust in government pension policy more generally

Adam Smith’s Green Thumb and Malthus’ Three Horsemen: Cautionary tales from classical political economy

This essay identifies a contradiction between the flourishing interest in the environmental economics of the classical period and a lack of critical parsing of the works of its leading representatives. Its focus is the work of Adam Smith and Thomas Malthus. It offers a critical analysis of their contribution to environmental thought and surveys the work of their contemporary devotees. It scrutinizes Smith's contribution to what Karl Polanyi termed the "economistic fallacy," as well as his defenses of class hierarchy, the "growth imperative" and consumerism. It subjects to critical appraisal Malthus's enthusiasm for private property and the market system, and his opposition to market regulation. While Malthus's principal attraction to ecological economists lies in his having allegedly broadened the scope of economics, and in his narrative of scarcity, this article shows that he, in fact, narrowed the scope of the discipline and conceptualized scarcity in a reified and pseudo-scientific way