We suppose that, stage by stage in causal processes, causes engage in activities that bring about their effects. These should be maximally vividly described when representing causal processes. We thus follow G. E. M. Anscombe, recent work in philosophy of biology on mechanisms, process tracing and realist evaluation in rejecting the Humean approach to causation, which eschews activities. Activities are interpreted as continuous processes afforded by the arrangements of the underlying system in which they take place. We illustrate here how to include activities in our original ‘boxes-and-arrows’ diagrams.

A ‘thick’ theory of singular causation, incorporating enough detail to allow you to know how to evidence singular causation, is required for empirical investigation of singular causal claims. The term ‘mechanism’ is often employed in describing how a cause produces its effect on any particular occasion. Here we point out that this term is ambiguous between the step-by-step process by which a cause produces an outcome, the underlying conditions that afford causal processes and the causal principles under which causes produce their effects.

Exploring the use of our methods has highlighted the importance of defining the boundaries of the system being studied and attending to features of underlying systems that afford causal processes. We note that our limited application of our methods cannot confirm that all the implementation actions were necessary, though our examination of L shows how this might be shown by broader study. We note that, while our methods may seem daunting, they’re no more detailed than statistical methods used in quantitative research and have practical advantages in supplying more detailed qualitative evaluations. They may also be used for ex ante appraisal. We stress the importance of understanding mechanisms in practical research and note that actual research involves back-and-forth between evidence and theories of change, even though we detail the former first in our evaluation. We note the value of such evaluations in combatting problems such as, relevantly, costly failed reforms.

Very few, if any, causal processes are self-standing – rather, they depend on features of ‘underlying systems’: sufficiently stable physical, socio-economic, legal and cultural conditions that afford such processes (‘mechanisms’ in some New Mechanists’ terms). The underlying system is whatever it is in the world that affords the causal process – a structure exhibiting sufficient stability that affords the causal activities that occur within the process and the principles that govern them. This is illustrated by Rube Goldberg machines and examples from biochemistry, economics and deskilling in child protection. Underlying systems are helpfully understood through assessing their components and features, and the affordances associated with them, with the boundaries of the underlying system considered pragmatically.

Antipsychotics effective for schizophrenia approved prior to 2024 shared the common mechanismof postsynaptic dopamine D2 receptor antagonism or partial agonism. Positive psychosis symptoms correlate with excessive presynaptic dopamine turnover and release, yet this postsynaptic mechanism improved positive symptoms only in some patients, and with concomitant risk for off-target motor and endocrine adverse effects; moreover, these agents showed no benefit for negative symptoms and cognitive dysfunction. The sole exception was data supporting cariprazine’s superiority to risperidone for negative symptoms. The muscarinic M1/M4 agonist xanomeline was approved in September 2024 and represents the first of a new antipsychotic class. This novel mechanism improves positive symptoms by reducing presynaptic dopamine release. Xanomeline also lacks anyD2 receptor affinity and is not associated with motor or endocrine side effects. Of importance, xanomeline treated patients with higher baseline levels of cognitive dysfunction in clinical trials data saw cognitive improvement, a finding likely related to stimulation of muscarinicM1 receptors. Treatment resistance is seen in one-third of schizophrenia patients. These individuals do not have dopamine dysfunction underlying their positive symptoms, and therefore show limited response to antipsychotics that target dopamine neurotransmission. Clozapine remains the only medication with proven efficacy for resistant schizophrenia, and with unique benefits for persistent impulsive aggression and suicidality. New molecules are being studied to address the array of positive, negative and cognitive symptoms of schizophrenia; however, until their approval, clinicians must be familiar with currently available agents and be adept at prescribing clozapine.

Comedy is the least considered aspect of modernist theatre – commonly framed as formally conservative and crowd-pleasing, leading towards harmony and continuity rather than rupture. However, comedy’s distinguishing features ally it to core modernist techniques and concerns: metatheatrical self-consciousness, disjunctions, disruptions, repetitions, and anarchic pleasures. Comic structures from farce and the comedy of manners to jokes, sketches, knockabout, and punchlines are central to a wide range of modernist plays. From Ibsen and Chekhov onward, the tragicomic mode is a common keynote of modernist theatre with the balance between comedy and tragedy dependent on the choices of the performer or the sensibilities of the viewer. Far from being inherently conventional, comedy can be viewed as modernist in its impulse to satirise and destabilise. Comedy is perhaps where the distinction between modernist and simply modern, between oppositional avant-garde and popular mainstream, is least identifiable and most intriguing.

This chapter surveys influential ideas about scientific explanation. The idea that scientific explanation is a matter of logical deduction from scientific laws has played an important role both as the basis for positive accounts of scientific explanation and as a target of critical arguments spurring the investigation of alternative views. The chapter reviews some of the reasons in favor holding such a covering-law view of explanation and then turn to some alternatives. The chapter also considers a pragmatically oriented account of the act of explaining. Another alternative focuses on the idea that explanations unify phenomena, showing how seemingly different things are manifestations of a single truth about nature. Several approaches emphasize the way explanations indicate what causes something to happen, whether by reference to a process, a possible manipulation, or a mechanism.

Since the Greeks, our world has been understood in terms of one of two root metaphors – the world as an organism (“organicism”) and the world as a machine (“mechanism”). With the coming of evolutionary ideas in the eighteenth century, we see that there are interpretations in terms of both metaphors.

The chapter delves into the specific kind of understanding aimed at in medicine, starting from the Understanding Thesis. Drawing on recent work by Broadbent (2019), debates in the epistemology of understanding (Kvanvig 2009; Grimm 2012; Khalifa 2017), and scholarship on the aims of inquiry, the chapter unpacks what it means to understand something, differentiating types of understanding, and using the history of scurvy to explore understanding a disease in medicine. The hypothesis is that biomedical understanding of a disease requires grasping a mechanistic explanation of the disease. This understanding of causal and constitutive relationships draws on an influential account of causation (Woodward 2003; 2010; 2015) and work on mechanistic explanations in biological sciences and neuroscience (Thagard 2003; 2005; Craver 2007; Nervi 2010; Kaplan and Craver 2011; Darrason 2018). However, it argues that biomedical understanding is necessary but not sufficient for clinical understanding, which combines biomedical understanding of a disease with personal understanding of an illness. This chapter revisits the distinction between "understanding" and "explanation" from debates in the field.