Positive and negative feedback: striking a balance between necessary antagonists

Most biological regulation systems comprise feedback circuits as crucial components. Negative feedback circuits have been well understood for a very long time; indeed, their understanding has been the basis for the engineering of cybernetic machines exhibiting stable behaviour. The importance of positive feedback circuits, considered as "vicious circles", has however been underestimated. In this article, we give a demonstration based on degree theory for vector fields of the conjecture, made by René Thomas, that the presence of positive feedback circuits is a necessary condition for autonomous differential systems, covering a wide class of biologically relevant systems, to possess multiple steady states. We also show ways to derive constraints on the weights of positive and negative feedback circuits. These qualitative and quantitative results provide, respectively, structural constraints (i.e. related to the interaction graph) and numerical constraints (i.e. related to the magnitudes of the interactions) on systems exhibiting complex behaviours, and should make it easier to reverse-engineer the interaction networks animating those systems on the basis of partial, sometimes unreliable, experimental data. We illustrate these concepts on a model multistable switch, in the context of cellular differentiation, showing a requirement for sufficient cooperativity. Further developments are expected in the discovery and modelling of regulatory networks in general, and in the interpretation of bio-array hybridization and proteomics experiments in particular.     

Morals, Medicine and Change: Morality Brokers, Social Phobias, and French Psychiatry

This paper will examine how French neurotics are being transformed into 'social phobics' and how the appearance of this group may be tied to new personal and social ideals. There are many people and factors that contribute to this changing definition of mental illness. Amongst these, I will focus on the role of three groups who are most vocally acting as morality brokers in the creation of these new subjects: psychiatrists, patients' groups and pharmaceutical companies.     

A necessary condition for balance of a block design

It is shown that, barring orthogonal designs, a necessary condition for a block design, BD(v, b, N), to be J-balanced is that the rows of its incidence matrix, N, are linearly independent. This strengthens the condition b v known in the literature as FISHER'S inequality. V-balanced block designs are also discussed.     

The Garland Encyclopedia of World Music: Africa

The Garland Encyclopedia of World Music: Africa. Ruth Stone. ed. New York: Garland, 1998. 852 pp., scores, and CD.     

The mathematical biophysics of some mental phenomena: II. Anxieties and elations

A neural mechanism is discussed which explains certain states of anxieties, in which an individual is worried about things which may be possible, but are exceedingly improbable. Certain quantitative relations are derived.Mutatis mutandis similar considerations apply to some states of elations. An application to certain types of paranoia is discussed.     

Cinema Itself: Cinephobia,Filmic Anxieties,and Ontologies of the Moving Image in Pakistan

Anxieties over the particular ontology and materiality of the film image—rather than moral concerns over the co-mingling of bodies in the built and social space of the cinema—have been addressed by two formative figures in the philosophy of Pakistan as a political and religious idea: Muhammad Iqbal and Syed Abul A'la Maududi. Their arguments provide two divergent examples of the ways in which the permissibility of film in Pakistan has been expressed. This essay is driven by such instances in which the epistemology—and in some cases permissibility—of technological objects is negotiated via their very ontology.     

Encyclopedia of Precolonial Africa: Archaeology, History, Languages, Cultures, and Environments

Encyclopedia of Precolonial Africa: Archaeology, History, Languages, Cultures, and Environments. Joseph O. Vogel. ed. Walnut Creek, CA: AltaMira Press, 1997.606 pp.     

The Cambridge Encyclopedia of Human Paleopathology

The Cambridge Encyclopedia of Human Paleopathology. Arthur C. Aufderheide and Conrado Rodriguez-Martin. Cambridge: Cambridge University Press. 1998. 478 pp.     

Development and Validation of a Questionnaire Assessing Fears and Beliefs of Patients with Knee Osteoarthritis: The Knee Osteoarthritis Fears and Beliefs Questionnaire (KOFBeQ)

Objective

We aimed to develop a questionnaire assessing fears and beliefs of patients with knee OA.

Design

We sent a detailed document reporting on a qualitative analysis of interviews of patients with knee OA to experts, and a Delphi procedure was adopted for item generation. Then, 80 physicians recruited 566 patients with knee OA to test the provisional questionnaire. Items were reduced according to their metric properties and exploratory factor analysis. Reliability was tested by the Cronbach α coefficient. Construct validity was tested by divergent validity and confirmatory factor analysis. Test–retest reliability was assessed by the intra-class correlation coefficient (ICC) and the Bland and Altman technique.

Results

137 items were extracted from analysis of the interview data. Three Delphi rounds were needed to obtain consensus on a 25-item provisional questionnaire. The item-reduction process resulted in an 11-item questionnaire. Selected items represented fears and beliefs about daily living activities (3 items), fears and beliefs about physicians (4 items), fears and beliefs about the disease (2 items), and fears and beliefs about sports and leisure activities (2 items). The Cronbach α coefficient of global score was 0.85. We observed expected divergent validity. Confirmation factor analyses confirmed higher intra-factor than inter-factor correlations. Test–retest reliability was good, with an ICC of 0.81, and Bland and Altman analysis did not reveal a systematic trend.

Conclusions

We propose an 11-item questionnaire assessing patients'' fears and beliefs concerning knee OA with good content and construct validity.