When an irresistible epistemology meets an immovable ontology.
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Behavior↗
Biomedical subjects
J C Wakefield
Publications and source records attributed to J C Wakefield.
CooC and CooD are required for assembly of CS1 pili.
Many strains of enterotoxigenic Escherichia coli (ETEC) isolated from patients with diarrhoeal disease exhibit CS1 pili on their surfaces. These appendages, which are thought to be important for colonization of the upper intestine, are composed largely of multiple identical protein subunits encoded by cooA. We have sequenced the DNA directly downstream of cooA and identified two open reading frames, cooC and cooD, transcribed in the same direction as cooB and cooA. Following cooD is DNA homologous to an insertion sequence, so cooB, A, C and D appear to encode all the information needed for E. coli K-12 to synthesize CS1 pili. Complementation analysis of mutants cloned in E. coli K-12 and constructed in an ETEC-derived strain indicates that cooC and cooD are not required for stability of the major CS1 pilin protein or for its transport to the periplasm, but, like cooB, both are needed for assembly of cooA into pili.
Amino Acid Sequence↗
Limits of operationalization: a critique of Spitzer and Endicott's (1978) proposed operational criteria for mental disorder.
Spitzer and Endicott (1978) proposed an operational definition of mental disorder that is a more rigorous version of the brief definitions that appeared in the 3rd and revised 3rd editions of the Diagnostic and Statistical Manual of Mental Disorders. The heart of their proposal is a translation of the concept of dysfunction into operational terms. I argue that their definition fails to capture the concept of dysfunction and is subject to many counterexamples. I use my harmful dysfunction account of disorder (Wakefield, 1992a, 1992b), which interprets dysfunction in evolutionary terms, to explain both the appeal and the problems of Spitzer and Endicott's definition and to provide support for the harmful dysfunction view. I conclude that the failure of Spitzer and Endicott's sophisticated attempt at operationalization indicates that nonoperational definitions that use functional concepts must play a role in formulating valid diagnostic criteria.
Adaptation, Psychological↗
The concept of mental disorder. On the boundary between biological facts and social values.
Although the concept of mental disorder is fundamental to theory and practice in the mental health field, no agreed on and adequate analysis of this concept currently exists. I argue that a disorder is a harmful dysfunction, wherein harmful is a value term based on social norms, and dysfunction is a scientific term referring to the failure of a mental mechanism to perform a natural function for which it was designed by evolution. Thus, the concept of disorder combines value and scientific components. Six other accounts of disorder are evaluated, including the skeptical antipsychiatric view, the value approach, disorder as whatever professionals treat, two scientific approaches (statistical deviance and biological disadvantage), and the operational definition of disorder as "unexpectable distress or disability" in the revised third edition of the Diagnostic and Statistical Manual of Mental Disorders (American Psychiatric Association, 1987). The harmful dysfunction analysis is shown to avoid the problems while preserving the insights of these other approaches.
Activities of Daily Living↗
Disorder as harmful dysfunction: a conceptual critique of DSM-III-R's definition of mental disorder.
The Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; DSM-III-R) operationally defines disorder essentially as "statistically unexpectable distress or disability." This definition is an attempt to operationalize 2 basic principles: that a disorder is harmful and that a disorder is a dysfunction (i.e., an inability of some internal mechanism to perform its natural function). However, the definition fails to capture the idea of "dysfunction" and so fails to validly distinguish disorders from nondisorders, leading to invalidities in many of DSM-III-R's specific diagnostic criteria. These problems with validity are traced to DSM-III-R's strategies for increasing reliability.
Humans↗
CooB is required for assembly but not transport of CS1 pilin.
CS1 pili are filamentous proteinaceous appendages found on many enterotoxigenic Escherichia coli (ETEC) strains isolated from human diarrhoeal disease. They are thought to effect colonization of the upper intestine by facilitating binding to human ileal epithelial cells. We have identified a gene, cooB, which lies directly upstream of cooA, the gene that encodes the major structural CS1 protein. When translated in vitro, the protein product of cooB migrates in sodium dodecyl sulphate/polyacrylamide gel with an apparent molecular mass of 26 kDa, which is consistent with that predicted from its DNA sequence. We constructed a mutant allele (cooB-1) by insertion of the omega fragment, which inhibits transcription and translation, into the cooB gene in vitro. In a derivative of an ETEC strain with the cooB-1 mutation (JEF100) and a plasmid that encodes Rns (pEU2030), the positive regulator required for CS1 expression, no cooB and a greatly reduced level of cooA product was detectable in total cell extracts. The reduction of cooA in this strain appears to result from polarity of the cooB mutation because introduction of the wild-type cooA gene in trans causes production of CooA protein, which is found in cell pellet extracts, in extracts containing only surface proteins and in the culture supernatant. Therefore, in the absence of CooB, CooA is stable and it is transported through both inner and outer membranes. However, the cooB-1 strain with cooA in trans does not cause haemagglutination of bovine erythrocytes (the model system used to assay adherence mediated by coli surface antigen 1 (CS1) pili).(ABSTRACT TRUNCATED AT 250 WORDS)
Antigens, Bacterial↗
Hierarchical models for multicentre binary response studies.
A three-stage hierarchical model is proposed for two treatment, binary response studies conducted in a number of centres. The approach adopted is Bayesian. Marginal densities for second stage parameters are shown to provide useful summaries both of comparative efficacy and of the heterogeneity of treatment effects across centres. Sensitivity studies of model assumptions are illustrated.
Bayes Theorem↗
Sex bias in the diagnosis of primary orgasmic dysfunction.
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Female↗
The semantics of success: do masturbation exercises lead to partner orgasm?
Do masturbation exercises assigned in preorgasmic women's groups enable previously nonorgasmic women to achieve orgasms during partner sex? Studies by Wallace and Barbach and Ersner-Hershfield and Kopel report encouraging partner orgasmic success rates of 87% and 82%, respectively, and these figures are commonly cited in reviews of the literature. I argue that these rates are misleading because they reflect overly liberal research definitions of "nonorgasmic," "orgasmic success," and "partner orgasm." A reanalysis of Ersner-Hershfield and Kopel's data using more stringent and intuitive criteria yields a partner success rate at 10 weeks after termination of 20% (or 47%, if women who require the use of a vibrator to have orgasm during partner sex are included as successes), as opposed to their original figure of 82%. These results suggest that masturbation training in preorgasmic women's groups is not the treatment of choice for most previously nonorgasmic women seeking partner orgasm. They also illustrate how different ideological conceptions of the meaning of sex can lead to different definitions of outcome categories and different evaluations of the same data.
Coitus↗
Statistical issues in the analysis of disease mapping data.
In this paper we discuss a number of issues that are pertinent to the analysis of disease mapping data. As an illustrative example we consider the mapping of larynx cancer across electoral wards in the North West Thames region of the U.K. Bayesian hierarchical models are now frequently employed to carry out such mapping. In a typical situation, a three-stage hierarchical model is specified in which the data are modelled as a function of area-specific relative risks at stage one; the collection of relative risks across the study region are modelled at stage two; and at stage three prior distributions are assigned to parameters of the stage two distribution. Such models allow area-specific disease relative risks to be 'smoothed' towards global and/or local mean levels across the study region. However, these models contain many structural and functional assumptions at different levels of the hierarchy; we aim to discuss some of these assumptions and illustrate their sensitivity. When relative risks are the endpoint of interest, it is common practice to assume that, for each of the age-sex strata of a particular area, there is a common multiplier (the relative risk) acting upon each of the stratum-specific risks in that area; we will examine this proportionality assumption. We also consider the choices of models and priors at stages two and three of the hierarchy, the effect of outlying areas, and an assessment of the level of smoothing that is being carried out. For inference, we concentrate on the description of the spatial variability in relative risks and on the association between the relative risks of larynx cancer and an area-level measure of socio-economic status.
Age Factors↗