Proponents of evidence-based medicine and some philosophers of science seem to agree that knowledge of mechanisms can help solve the problem of applying results of controlled studies to target populations (‘the problem of extrapolation’). We describe the problem of extrapolation, characterize mechanisms, and outline how mechanistic knowledge might be used to solve the problem. Our main thesis is that there are four often overlooked problems with using mechanistic knowledge to solve the problem of extrapolation. First, our understanding of mechanisms is (...) often (and arguably, likely to remain) incomplete. Secondly, knowledge of mechanisms is not always applicable outside the tightly controlled laboratory conditions in which it is gained. Thirdly, mechanisms can behave paradoxically. Fourthly, as Daniel Steel points out, using mechanistic knowledge faces the problem of the ‘extrapolator’s circle’. At the same time, when the problems with mechanistic knowledge have been addressed, such knowledge can and should be used to mitigate (nothing can entirely solve) the problem of extrapolation. (shrink)

In this paper, I analyze George Gaylord Simpson's response to the molecularization of evolutionary biology from his unique perspective as a paleontologist. I do so by exploring his views on early attempts to reconstruct phylogenetic relationships among primates using molecular data. Particular attention is paid to Simpson's role in the evolutionary synthesis of the 1930s and 1940s, as well as his concerns about the rise of molecular biology as a powerful discipline and world-view in the 1960s. I argue that Simpson's (...) belief in the supremacy of natural selection as the primary driving force of evolution, as well as his view that biology was a historical science that seeks ultimate causes and highlights contingency, prevented him from acknowledging that the study of molecular evolution was an inherently valuable part of the life sciences. (shrink)

Drawing on a qualitative study of women who cared for their elderly mothers, this article explores women's experiences of feeling responsible for elderly relatives. The minimal provision of public services for old people and the relative absence of brothers and husbands from family caregiving emerge as material constraints shaping women's sense of obligation. This is affirmed by ideologies and assumptions about women's association with caring and family ties that permeate subjects' accounts of their situations. Translating their sense of obligation into (...) their lives is a contradictory process characterized by ambivalence and guilt that stifle complaint. Further exploration of the social processes that sustain the inequitable division of caring labor can contribute to interpretations, practices, and policies that benefit rather than constrain women. (shrink)

Community care for frail elderly people rests heavily on the work of low-status, paraprofessional home care workers. Home care workers describe their work as highly personalized caring labor that often seeps out of its formal boundaries into informal, unpaid activities. Although these activities are valued by workers, their supervisors, elderly clients, and family members, they represent uncompensated and exploited labor. Cost-cutting trends in home care management that seek to depersonalize home care labor are likely to increase its exploitative potential for (...) paid care workers and, simultaneously, to disadvantage and jeopardize elderly home care clients and their unpaid family caregivers. (shrink)

Larry Laudan has challenged the realist to come up with a program that submits realism to "those stringent empirical demands which the realist himself minimally insists on when appraising scientific theories." This paper shows how the realist can go about taking up Laudan on this challenge; and, in such a way that the realist hypothesis actually ends up being confirmed, by any empirical standards. In other words, it is shown that we can test for convergent realism, just as readily as (...) Laudan can test for a connection between theories that are controlled by the cannons of science and their subsequent reliability. (shrink)

Evidence-based medicine (EBM), the dominant approach to assessing the effectiveness of clinical and public health interventions, focuses on the results of association studies. EBM+ is a development of EBM that systematically considers mechanistic studies alongside association studies. In this paper we provide several examples of the importance of mechanistic evidence to coronavirus research. (i) Assessment of combination therapy for MERS highlights the need for systematic assessment of mechanistic evidence. (ii) That hypertension is a risk factor for severe disease in the (...) case of SARS-CoV-2 suggests that altering hypertension treatment might alleviate disease, but the mechanisms are complex, and it is essential to consider and evaluate multiple mechanistic hypotheses. (iii) To be confident that public health interventions will be effective requires a detailed assessment of social and psychological components of the mechanisms of their action, in addition to mechanisms of disease. (iv) In particular, if vaccination programmes are to be effective, they must be carefully tailored to the social context; again, mechanistic evidence is crucial. We conclude that coronavirus research is best situated within the EBM+ evaluation framework. (shrink)

In “A Confutation of Convergent Realism,” Larry Laudan presents the realist with these fascinating challenges:What,then,of realism itself as a ‘scientific’ hypothesis?…If realism has made some novel predictions or been subjected to carefully controlled tests, one does not learn about it from the literature of contemporary realism. (1981, p. 46.)He then goes on to say:No proponent of realism has sought to show that realism satisfies those stringent empirical demands which the realist himself minimally insists on when appraising scientific theories. (1981, p. (...) 46)Not only do I fully endorse what Laudan says in these passages, I think it is time to take him up on these challenges.Laudan’s position has been that scientific progress can be explained without having to appeal to verisimilitude. Instead, we explain the success of a scientific theory in terms of its subjugation to the cannons of experimental controls: those theories that have been put through proper testing during the course of their formulation are the ones that are most likely to be reliable. (1984, pp. 96-101). (shrink)

The role of mechanistic evidence tends to be under-appreciated in current evidencebased medicine (EBM), which focusses on clinical studies, tending to restrict attention to randomized controlled studies (RCTs) when they are available. The EBM+ programme seeks to redress this imbalance, by suggesting methods for evaluating mechanistic studies alongside clinical studies. Drug approval is a problematic case for the view that mechanistic evidence should be taken into account, because RCTs are almost always available. Nevertheless, we argue that mechanistic evidence is central (...) to all the key tasks in the drug approval process: in drug discovery and development; assessing pharmaceutical quality; devising dosage regimens; assessing efficacy, harms, external validity, and cost-effectiveness; evaluating adherence; and extending product licences. We recommend that, when preparing for meetings in which any aspect of drug approval is to be discussed, mechanistic evidence should be systematically analysed and presented to the committee members alongside analyses of clinical studies. (shrink)

Alzheimer's disease (AD) is the most common cause of dementia, and there is currently no cure. The “β‐amyloid cascade hypothesis” of AD is the basis of current understanding of AD pathogenesis and drug discovery. However, no AD models have fully validated this hypothesis. We recently developed a human stem cell culture model of AD by cultivating genetically modified human neural stem cells in a three‐dimensional (3D) cell culture system. These cells were able to recapitulate key events of AD pathology including (...) β‐amyloid plaques and neurofibrillary tangles. In this review, we will discuss the progress and current limitations of AD mouse models and human stem cell models as well as explore the breakthroughs of 3D cell culture systems. We will also share our perspective on the potential of dish models of neurodegenerative diseases for studying pathogenic cascades and therapeutic drug discovery. (shrink)