353 research outputs found
Crises and collective socio-economic phenomena: simple models and challenges
Financial and economic history is strewn with bubbles and crashes, booms and
busts, crises and upheavals of all sorts. Understanding the origin of these
events is arguably one of the most important problems in economic theory. In
this paper, we review recent efforts to include heterogeneities and
interactions in models of decision. We argue that the Random Field Ising model
(RFIM) indeed provides a unifying framework to account for many collective
socio-economic phenomena that lead to sudden ruptures and crises. We discuss
different models that can capture potentially destabilising self-referential
feedback loops, induced either by herding, i.e. reference to peers, or
trending, i.e. reference to the past, and account for some of the phenomenology
missing in the standard models. We discuss some empirically testable
predictions of these models, for example robust signatures of RFIM-like herding
effects, or the logarithmic decay of spatial correlations of voting patterns.
One of the most striking result, inspired by statistical physics methods, is
that Adam Smith's invisible hand can badly fail at solving simple coordination
problems. We also insist on the issue of time-scales, that can be extremely
long in some cases, and prevent socially optimal equilibria to be reached. As a
theoretical challenge, the study of so-called "detailed-balance" violating
decision rules is needed to decide whether conclusions based on current models
(that all assume detailed-balance) are indeed robust and generic.Comment: Review paper accepted for a special issue of J Stat Phys; several
minor improvements along reviewers' comment
SWITCHING RATES AND THE ASYMPTOTIC BEHAVIOR OF HERDING MODELS
Markov chains have experienced a surge of economic interest in the form of behavioral agent-based models that aim at explaining the statistical regularities of financial returns. We review some of the relevant mathematical facts and show how they apply to agent-based herding models, with the particular goal of establishing their asymptotic behavior because several studies have pointed out that the ability of such models to reproduce the stylized facts hinges crucially on the size of the agent population (typically denoted by n), a phenomenon that is also known as n-dependence. Our main finding is that n-(in)dependence traces back to both the topology and the velocity of information transmission among heterogeneous financial agents
Minimally invasive surgery and cancer: controversies part 1
Perhaps there is no more important issue in the care of surgical patients than the appropriate use of minimally invasive surgery (MIS) for patients with cancer. Important advances in surgical technique have an impact on early perioperative morbidity, length of hospital stay, pain management, and quality of life issues, as clearly proved with MIS. However, for oncology patients, historically, the most important clinical questions have been answered in the context of prospective randomized trials. Important considerations for MIS and cancer have been addressed, such as what are the important immunologic consequences of MIS versus open surgery and what is the role of laparoscopy in the staging of gastrointestinal cancers? This review article discusses many of the key controversies in the minimally invasive treatment of cancer using the proâcon debate format
Native human autoantibodies targeting GIPC1 identify differential expression in malignant tumors of the breast and ovary
<p>Abstract</p> <p>Background</p> <p>We have been studying the native humoral immune response to cancer and have isolated a library of fully human autoantibodies to a variety of malignancies. We previously described the isolation and characterization of two fully human monoclonal antibodies, 27.F7 and 27.B1, from breast cancer patients that target the protein known as GIPC1, an accessory PDZ-domain binding protein involved in regulation of G-protein signaling. Human monoclonal antibodies, 27.F7 and 27.B1, to GIPC1 demonstrate specific binding to malignant breast cancer tissue with no reactivity with normal breast tissue.</p> <p>Methods</p> <p>The current study employs cELISA, flow cytometry, Western blot analysis as well as immunocytochemistry, and immunohistochemistry. Data is analyzed statistically with the Fisher one-tail and two-tail tests for two independent samples.</p> <p>Results</p> <p>By screening several other cancer cell lines with 27.F7 and 27.B1 we found consistently strong staining of other human cancer cell lines including SKOV-3 (an ovarian cancer cell line). To further clarify the association of GIPC1 with breast and ovarian cancer we carefully studied 27.F7 and 27.B1 using immunocytochemical and immunohistochemical techniques. An immunohistochemical study of normal ovarian tissue, benign, borderline and malignant ovarian serous tumors, and different types of breast cancer revealed high expression of GIPC1 protein in neoplastic cells. Interestingly, antibodies 27.F7 and 27.B1 demonstrate differential staining of borderline ovarian tumors. Examination of different types of breast cancer demonstrates that the level of GIPC1 expression depends on tumor invasiveness and displays a higher expression than in benign tumors.</p> <p>Conclusion</p> <p>The present pilot study demonstrates that the GIPC1 protein is overexpressed in ovarian and breast cancer, which may provide an important diagnostic and prognostic marker and will constitute the basis for further study of the role that this protein plays in malignant diseases. In addition, this study suggests that human monoclonal antibodies 27.F7 and 27.B1 should be further evaluated as potential diagnostic tools.</p
Quantitative association tests of immune responses to antigens of Mycobacterium tuberculosis: a study of twins in West Africa.
There is now considerable evidence that host genetic factors are important in determining the outcome of infection with Mycobacterium tuberculosis (MTB). The aim of this study was to assess the role of several candidate genes in the variation observed in the immune responses to MTB antigens. In-vitro assays of T-cell proliferation, an in-vivo intradermal delayed hypersensitivity response; cytokine and antibody secretions to several mycobacterial peptide antigens were assessed in healthy, but exposed, West African twins. Candidate gene polymorphisms were typed in the NRAMP1, Vitamin D receptor, IL10, IL4, IL4 receptor and CTLA-4 genes. Variants of the loci IL10 (-1082 G/A), CTLA-4 (49 A/G) and the IL4 receptor (128 A/G) showed significant associations with immune responses to several antigens. T-cell proliferative responses and antibody responses were reduced, TNF-alpha responses were increased for subjects with the CTLA-4 G allele. The T-cell proliferative responses of subjects with IL10 GA and GG genotypes differed significantly. IL4 receptor AG and GG genotypes also showed significant differences in their T-cell proliferative responses to MTB antigens. These results yield a greater understanding of the genetic mechanisms that underlie the immune responses in tuberculosis and have implications for the design of therapeutic interventions
A Semi-Physiologically Based Pharmacokinetic Model Describing the Altered Metabolism of Midazolam Due to Inflammation in Mice
This is the author's accepted manuscript.Purpose
To investigate influence of inflammation on metabolism and pharmacokinetics (PK) of midazolam (MDZ) and construct a semi-physiologically based pharmacokinetic (PBPK) model to predict PK in mice with inflammatory disease.
Methods
Glucose-6-phosphate isomerase (GPI)-mediated inflammation was used as a preclinical model of arthritis in DBA/1 mice. CYP3A substrate MDZ was selected to study changes in metabolism and PK during the inflammation. The semi-PBPK model was constructed using mouse physiological parameters, liver microsome metabolism, and healthy animal PK data. In addition, serum cytokine, and liver-CYP (cytochrome P450 enzymes) mRNA levels were examined.
Results
The in vitro metabolite formation rate was suppressed in liver microsomes prepared from the GPI-treated mice as compared to the healthy mice. Further, clearance of MDZ was reduced during inflammation as compared to the healthy group. Finally, the semi-PBPK model was used to predict PK of MDZ after GPI-mediated inflammation. IL-6 and TNF-α levels were elevated and liver-cyp3a11 mRNA was reduced after GPI treatment.
Conclusion
The semi-PBPK model successfully predicted PK parameters of MDZ in the disease state. The model may be applied to predict PK of other drugs under disease conditions using healthy animal PK and liver microsomal data as inputs
Ants in a Labyrinth: A Statistical Mechanics Approach to the Division of Labour
Division of labour (DoL) is a fundamental organisational principle in human
societies, within virtual and robotic swarms and at all levels of biological
organisation. DoL reaches a pinnacle in the insect societies where the most
widely used model is based on variation in response thresholds among
individuals, and the assumption that individuals and stimuli are well-mixed.
Here, we present a spatially explicit model of DoL. Our model is inspired by
Pierre de Gennes' 'Ant in a Labyrinth' which laid the foundations
of an entire new field in statistical mechanics. We demonstrate the emergence,
even in a simplified one-dimensional model, of a spatial patterning of
individuals and a right-skewed activity distribution, both of which are
characteristics of division of labour in animal societies. We then show using a
two-dimensional model that the work done by an individual within an activity
bout is a sigmoidal function of its response threshold. Furthermore, there is an
inverse relationship between the overall stimulus level and the skewness of the
activity distribution. Therefore, the difference in the amount of work done by
two individuals with different thresholds increases as the overall stimulus
level decreases. Indeed, spatial fluctuations of task stimuli are minimised at
these low stimulus levels. Hence, the more unequally labour is divided amongst
individuals, the greater the ability of the colony to maintain homeostasis.
Finally, we show that the non-random spatial distribution of individuals within
biological and social systems could be caused by indirect (stigmergic)
interactions, rather than direct agent-to-agent interactions. Our model links
the principle of DoL with principles in the statistical mechanics and provides
testable hypotheses for future experiments
A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)
Meeting abstrac
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