Statistical Inference and the Plethora of Probability Paradigms: A Principled Pluralism

The major competing statistical paradigms share a common remarkable but unremarked thread: in many of their inferential applications, different probability interpretations are combined. How this plays out in different theories of inference depends on the type of question asked. We distinguish four question types: confirmation, evidence, decision, and prediction. We show that Bayesian confirmation theory mixes what are intuitively “subjective” and “objective” interpretations of probability, whereas the likelihood-based account of evidence melds three conceptions of what constitutes an “objective” probability

The microbiome in wound repair and tissue fibrosis

Bacterial colonization occurs in all wounds, chronic or acute, and the break in epithelium integrity that defines a wound impairs the forces that shape and constrain the microbiome at that site. This review highlights the interactions between bacterial communities in the wound and the ultimate resolution of the wound or development of fibrotic lesions. Chronic wounds support complex microbial communities comprising a wide variety of bacterial phyla, genera, and species, including some fastidious anaerobic bacteria not identified using culture‐based methods. Thus, the complexity of bacterial communities in wounds has historically been underestimated. There are a number of intriguing possibilities to explain these results that may also provide novel insights into changes and adaptation of bacterial metabolic networks in inflamed and wounded mucosa, including the critical role of biofilm formation. It is well accepted that the heightened state of activation of host cells in a wound that is driven by the microbiota can certainly lead to detrimental effects on wound regeneration, but the microbiota of the wound may also have beneficial effects on wound healing. Studies in experimental systems have clearly demonstrated a beneficial effect for members of the gut microbiota on regulation of systemic inflammation, which could also impact wound healing at sites outside the gastrointestinal tract. The utilization of culture‐independent microbiology to characterize the microbiome of wounds and surrounding mucosa has raised many intriguing questions regarding previously held notions about the cause and effect relationships between bacterial colonization and wound repair and mechanisms involved in this symbiotic relationship.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95009/1/path4118.pd

A tale of two sites: how inflammation can reshape the microbiomes of the gut and lungs

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141495/1/jlb0943.pd

Mathematical modeling of cell population dynamics in the colonic crypt and in colorectal cancer

Colorectal cancer is initiated in colonic crypts. A succession of genetic mutations or epigenetic changes can lead to homeostasis in the crypt being overcome, and subsequent unbounded growth. We consider the dynamics of a single colorectal crypt by using a compartmental approach [Tomlinson IPM, Bodmer WF (1995) Proc Natl Acad Sci USA 92: 11130-11134], which accounts for populations of stem cells, differential cells, and transit cells. That original model made the simplifying assumptions that each cell popuation divides synchronously, but we relax these assumptions by adopting an age-structured approach that models asynchronous cell division, and by using a continuum model. We discuss two mechanims that could regulate the growth of cell numbers and maintain the equilibrium that is normally observed in the crypt. The first will always maintain an equilibrium for all parameter values, whereas the second can allow unbounded proliferation if the net per capita growth rates are large enough. Results show that an increase in cell renewal, which is equivalent to a failure of programmed cell death or of differentiation, can lead to the growth of cancers. The second model can be used to explain the long lag phases in tumor growth, during which news, higher equilibria are reached, before unlimited growth in cell number ensues

Serial characterisation of monocyte and neutrophil function after lung resection.

OBJECTIVES: The primary aim of this prospective study was to perform a comprehensive serial characterisation of monocyte and neutrophil function, circulating monocyte subsets, and bronchoalveolar lavage (BAL) fluid after lung resection. A secondary aim was to perform a pilot, hypothesis-generating evaluation of whether innate immune parameters were associated with postoperative pneumonia. METHODS: Forty patients undergoing lung resection were studied in detail. Blood monocytes and neutrophils were isolated preoperatively and at 6, 24 and 48 h postoperatively. BAL was performed preoperatively and immediately postoperatively. Monocyte subsets, monocyte responsiveness to lipopolysaccharide (LPS) and neutrophil phagocytic capacity were quantified at all time points. Differential cell count, protein and cytokine concentrations were measured in BAL. Pneumonia evaluation at 72 h was assessed using predefined criteria. RESULTS: After surgery, circulating subsets of classical and intermediate monocytes increased significantly. LPS-induced release of proinflammatory cytokines from monocytes increased significantly and by 48 h a more proinflammatory profile was found. Neutrophil phagocytosis demonstrated a small but significant fall. Factors associated with postoperative pneumonia were: increased release of specific proinflammatory and anti-inflammatory cytokines from monocytes; preoperative neutrophilia; and preoperative BAL cell count. CONCLUSIONS: We conclude that postoperative lung inflammation is associated with specific changes in the cellular innate immune response, a better understanding of which may improve patient selection and prediction of complications in the future

Hierarchical model for the scale-dependent velocity of seismic waves

Elastic waves of short wavelength propagating through the upper layer of the Earth appear to move faster at large separations of source and receiver than at short separations. This scale dependent velocity is a manifestation of Fermat's principle of least time in a medium with random velocity fluctuations. Existing perturbation theories predict a linear increase of the velocity shift with increasing separation, and cannot describe the saturation of the velocity shift at large separations that is seen in computer simulations. Here we show that this long-standing problem in seismology can be solved using a model developed originally in the context of polymer physics. We find that the saturation velocity scales with the four-third power of the root-mean-square amplitude of the velocity fluctuations, in good agreement with the computer simulations.Comment: 7 pages including 3 figure

Differential response to bacteria, and TOLLIP expression, in the human respiratory tract.

OBJECTIVES: The observation that pathogenic bacteria are commonly tolerated in the human nose, yet drive florid inflammation in the lung, is poorly understood, partly due to limited availability of primary human cells from each location. We compared responses to bacterial virulence factors in primary human nasal and alveolar cells, and characterised the distribution of Toll-interacting protein (TOLLIP; an inhibitor of Toll-like receptor (TLR) signalling) in the human respiratory tract. METHODS: Primary cells were isolated from nasal brushings and lung tissue taken from patients undergoing pulmonary resection. Cells were exposed to lipopolysaccharide, lipoteichoic acid, peptidoglycan, CpG-C DNA or tumour necrosis factor (TNF). Cytokines were measured in cell supernatants. TOLLIP was characterised using quantitative real-time PCR and immunofluorescence. RESULTS: In primary alveolar, but not primary nasal, cells peptidoglycan significantly increased secretion of interleukin (IL)-1β, IL-6, IL-8, IL-10 and TNF. TLR2 expression was significantly higher in alveolar cells and correlated with IL-8 production. TOLLIP expression was significantly greater in nasal cells. CONCLUSION: In conclusion, primary human alveolar epithelial cells are significantly more responsive to peptidoglycan than primary nasal epithelial cells. This may partly be explained by differential TLR2 expression. TOLLIP is expressed widely in the human respiratory tract, and may contribute to the regulation of inflammatory responses

Globalization, the ambivalence of European integration and the possibilities for a post-disciplinary EU studies

Using the work of Manuel Castells as a starting point, this article explores the ambivalent relationship between globalization and European integration and the variety of ways in which the mainstream political science of the EU has attempted to deal with this issue. The analysis here suggests that various 'mainstreaming' disciplinary norms induce types of work that fail to address fully the somewhat paradoxical and counter-intuitive range of possible relationships between globalization and European integration. The article explores critically four possible analytical ways out of this paradox—abandonment of the concept of globalization, the development of definition precision in globalization studies, the reorientation of work to focus on globalization as discourse, and inter- and post-disciplinarity. The argument suggests that orthodox discussions of the relationship require a notion of social geography that sits at odds with much of the literature on globalization and while greater dialogue between disciplines is to be welcomed, a series of profound epistemological questions need to be confronted if studies of the interplay between global and social process are to be liberated from their disciplinary chains

Jekyll and Hyde: men's constructions of feminism and feminists

Research and commentary on men's responses to feminism has demonstrated the range of ways in which men have mobilised both against and for feminist principles. This paper argues that further analyses of men's responses require a sophisticated theory of discourse acknowledging the fragmented and contradictory nature of representation. A corpus of men's talk on feminism and feminists was studied to identify the pervasive patterns in men's accounting and regularities in rhetorical organisation. Material from two samples of men was included: a sample of white middle-class 17-18 year old school students and a sample of 60 interviews with a more diverse sample of older men aged 20 to 64. Two interpretative repertoires of feminism and feminists were identified. These set up a 'Jekyll and Hyde' binary and positioned feminism along with feminists very differently as reasonable versus extreme and monstrous. Both repertoires tended to be deployed together and the paper explores the ideological and interactional consequences of typical deployments along with the identity work accomplished by the men as they positioned themselves in relation to these