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Trace amine-associated receptor 1 (TAAR1) agonists offer a new approach, but there is uncertainty regarding their effects, exact mechanism of action and potential role in treating psychosis.
Aims
To evaluate the available evidence on TAAR1 agonists in psychosis, using triangulation of the output of living systematic reviews (LSRs) of animal and human studies, and provide recommendations for future research prioritisation.
Method
This study is part of GALENOS (Global Alliance for Living Evidence on aNxiety, depressiOn and pSychosis). In the triangulation process, a multidisciplinary group of experts, including those with lived experience, met and appraised the first co-produced living systematic reviews from GALENOS, on TAAR1 agonists.
Results
The animal data suggested a potential antipsychotic effect, as TAAR1 agonists reduced locomotor activity induced by pro-psychotic drug treatment. Human studies showed few differences for ulotaront and ralmitaront compared with placebo in improving overall symptoms in adults with acute schizophrenia (four studies, n = 1291 participants, standardised mean difference (SMD) 0.15, 95% CI −0.05 to 0.34). Large placebo responses were seen in ulotaront phase three trials. Ralmitaront was less efficacious than risperidone (one study, n = 156 participants, SMD = −0.53, 95% CI −0.86 to −0.20). The side-effect profile of TAAR1 agonists was favourable compared with existing antipsychotics. Priorities for future studies included (a) using different animal models of psychosis with greater translational validity; (b) animal and human studies with wider outcomes including cognitive and affective symptoms and (c) mechanistic studies and investigations of other potential applications, such as adjunctive treatments and long-term outcomes. Recommendations for future iterations of the LSRs included (a) meta-analysis of individual human participant data, (b) including studies that used different methodologies and (c) assessing other disorders and symptoms.
Conclusions
This co-produced, international triangulation examined the available evidence and developed recommendations for future research and clinical applications for TAAR1 agonists in psychosis. Broader challenges included difficulties in assessing the risk of bias, reproducibility, translation and interpretability of animal models to clinical outcomes, and a lack of individual and clinical characteristics in the human data. The research will inform a separate, independent prioritisation process, led by lived experience experts, to prioritise directions for future research.
At the basis of many important research questions is causality – does X causally impact Y? For behavioural and psychiatric traits, answering such questions can be particularly challenging, as they are highly complex and multifactorial. ‘Triangulation’ refers to prospectively choosing, conducting and integrating several methods to investigate a specific causal question. If different methods, with different sources of bias, all indicate a causal effect, the finding is much less likely to be spurious. While triangulation can be a powerful approach, its interpretation differs across (sub)fields and there are no formal guidelines. Here, we aim to provide clarity and guidance around the process of triangulation for behavioural and psychiatric epidemiology, so that results of existing triangulation studies can be better interpreted, and new triangulation studies better designed.
Methods
We first introduce the concept of triangulation and how it is applied in epidemiological investigations of behavioural and psychiatric traits. Next, we put forth a systematic step-by-step guide, that can be used to design a triangulation study (accompanied by a worked example). Finally, we provide important general recommendations for future studies.
Results
While the literature contains varying interpretations, triangulation generally refers to an investigation that assesses the robustness of a potential causal finding by explicitly combining different approaches. This may include multiple types of statistical methods, the same method applied in multiple samples, or multiple different measurements of the variable(s) of interest. In behavioural and psychiatric epidemiology, triangulation commonly includes prospective cohort studies, natural experiments and/or genetically informative designs (including the increasingly popular method of Mendelian randomization). The guide that we propose aids the planning and interpreting of triangulation by prompting crucial considerations. Broadly, its steps are as follows: determine your causal question, draw a directed acyclic graph, identify available resources and samples, identify suitable methodological approaches, further specify the causal question for each method, explicate the effects of potential biases and, pre-specify expected results. We illustrated the guide’s use by considering the question: ‘Does maternal tobacco smoking during pregnancy cause offspring depression?’.
Conclusions
In the current era of big data, and with increasing (public) availability of large-scale datasets, triangulation will become increasingly relevant in identifying robust risk factors for adverse mental health outcomes. Our hope is that this review and guide will provide clarity and direction, as well as stimulate more researchers to apply triangulation to causal questions around behavioural and psychiatric traits.
This chapter describes the structure of mentalization-based treatment group therapy (MBT-G) for adults and adolescents, and explains how to focus on the mentalizing process in the group. Clinical examples are used for illustrative purposes throughout, and the progress of the patient who was described in Chapter 4 is discussed. The introduction of new patients, the processes of developing clinical values for the group, and the generation of epistemic trust within the group are outlined, and exercises that are designed to stimulate interpersonal mentalizing in the group are discussed.
To give a clear understanding of authoritarian learning, the chapter provides a research design and methodology for better investigating authoritarian learning. Using the four cases of Belarus, Moldova, Russia, and Ukraine we analyse the different aspects of authoritarian learning. Methodologically we use process-tracing and interviews to investigate the nuances of authoritarian learning. While not all the four case studies can be classified as authoritarian regimes, there are periods of attempted authoritarian consolidation in each and there are some elites with authoritarian tendencies across the four cases studied. The chapter offers research questions that the rest of the book will investigate to better understand the distinctions of authoritarian learning
This richly illustrated Element introduces the reader to the basic principles of archaeological mapping and planning. It presents both the mathematical and the practical backgrounds, as well as many tips and tricks. This will enable archaeologists to create acceptable maps and plans of archaeological remains, even with limited means of in adverse circumstances.
The introduction presents some general reflections on what characterises Heidegger’s fundamental ontology and what makes his thought a particularly promising point of departure for doing social ontology. I first introduce Heidegger’s holistic conceptions of Dasein and being-in-the-world by way of contrast to Cartesian atomism. I then go on to show that Heidegger conceives of intersubjectivity as a triangular relation between self, world, and other rather than a dyadic relation between two independent subjects. My claim is that Heidegger’s social ontology is found directly in his conception of the shared world and that his more well-known accounts of the Anyone and solicitude should be understood within this general framework. I also reflect on the relation between Heidegger’s social ontology and his politics and provide an outline of the book.
This chapter discusses whether Heidegger’s holism – roughly, the view that the meaning of the parts (entities) depends on the whole (the world) – entails a vicious relativism. I argue that Heidegger is a holist because he is committed to both object externalism (the view that intentional states depend on environmental objects) and social externalism (the view that intentional states depend on other people). Whether his holism entails relativism depends on how we understand these two commitments. Discussing recent interpretations of Heidegger’s holism (Lafont, Dreyfus, Okrent, Carman), I argue that Heidegger’s holism entails a form of relativism only if we take his social externalism to be a function of social conventions. I then go on to challenge that this is the case by arguing that Heidegger is an open-ended social externalist according to whom intentional states do not depend solely on our relation to social conventions (or any other particular social formation such as language or tradition) but on our on-going social interaction broadly construed.
In this chapter, I clarify, contextualise, and reassess Heidegger’s ambiguous and polemical account of social cognition. Although commentators often take his critique of, for instance, empathy to be pretty straightforward, a closer look reveals that Heidegger makes a number of seemingly incoherent claims. To clarify this, I identify six different objections raised by Heidegger against theories of social cognition and then reassess who (among both historical and contemporary contenders) are, in fact, vulnerable to these objections. Drawing on Fundamental Concepts of Metaphysics, I then go on to develop a positive, Heideggerian account of social cognition. I show that Heidegger’s view has much in common with phenomenological empathy theories but that he departs from these by arguing that we must understand the other as exhibiting a practical comportment that constitutively depends on our shared environment. Finally, I consider how our understanding of our fellow Dasein differs from our understanding of nonhuman animals.
We investigate a recently devised polyhedral semantics for intermediate logics, in which formulas are interpreted in n-dimensional polyhedra. An intermediate logic is polyhedrally complete if it is complete with respect to some class of polyhedra. The first main result of this paper is a necessary and sufficient condition for the polyhedral completeness of a logic. This condition, which we call the Nerve Criterion, is expressed in terms of Alexandrov’s notion of the nerve of a poset. It affords a purely combinatorial characterisation of polyhedrally complete logics. Using the Nerve Criterion we show, easily, that there are continuum many intermediate logics that are not polyhedrally complete but which have the finite model property. We also provide, at considerable combinatorial labour, a countably infinite class of logics axiomatised by the Jankov–Fine formulas of ‘starlike trees’ all of which are polyhedrally complete. The polyhedral completeness theorem for these ‘starlike logics’ is the second main result of this paper.
This chapter presents the case for employing Bayesianism as a universal, unified framework for inference that narrows the divide between qualitative versus quantitative data, within-case versus cross-case analysis, and observational versus experimental research. It offers a Bayesian critique of various other approaches to qualitative methods and multi-method research.
Edited by
Ruth Kircher, Mercator European Research Centre on Multilingualism and Language Learning, and Fryske Akademy, Netherlands,Lena Zipp, Universität Zürich
This chapter examines what research falls under the epithet of ‘mixed-methods’ and discusses the main advantages of conducting mixed-methods research. The chapter introduces the key issues of mixed-methods research planning and design: that is, the tackling of ontological and epistemological challenges, the equal weighting of methods, and the sequencing of methods. The chapter also provides information regarding the analysis of data resulting from mixed-methods research, and how this can be done in a manner that provides appropriate integration. The key issues of the chapter are illustrated by means of two case studies. The first investigates attitudes towards French and English in Montreal, making use of a questionnaire and a matched-guise experiment. This case study shows how mixed-methods approaches can lead to a deeper understanding of language attitudes as part of larger social processes in a manner that no one method on its own could do. The second case study examines attitudes towards Catalan in Northern Catalonia by means of interviews and variable analysis. This case study demonstrates how mixed-methods research allows for a broader representation of the attitudinal and ideological landscape of a specific language community than could be afforded by the use of one method alone.
An iterative square root of a self-map f is a self-map g such that
$g(g(\cdot ))=f(\cdot )$
. We obtain new characterizations for detecting the non-existence of such square roots for self-maps on arbitrary sets. They are used to prove that continuous self-maps with no square roots are dense in the space of all continuous self-maps for various topological spaces. The spaces studied include those that are homeomorphic to the unit cube in
${\mathbb R}^{m}$
and to the whole of
$\mathbb {R}^{m}$
for every positive integer
$m.$
However, we also prove that every continuous self-map on a space homeomorphic to the unit cube in
$\mathbb {R}^{m}$
with a fixed point on the boundary can be approximated by iterative squares of continuous self-maps.
We show that attending to domain considerations in corpus design involves three steps: (1) describing the domain as fully as possible; (2) operationalizing the domain; (3) sampling the texts. Describing the domain requires defining the boundaries of the domain: what texts belong within the domain and what do not? Describing the domain requires identifying important internal categories of texts that reflect qualitative variation within the domain. Domain description should be carried out systematically using a range of sources that can be evaluated for quality and triangulated. Operationalizing the domain refers to specifying the set of texts that are available for sampling; operational domains are always precisely bounded and specified. A sampling frame is an itemized list of all texts (from the operational domain) that are available for sampling. A sampling unit is the individual “object” (usually a text) that will be included in the corpus. Stratification is the process of collecting texts according to identified categories within the domain, and is usually desirable in corpus design. Proportionality refers to the relative sizes of strata within the sample. Strata can be proportional or equal-sized. Sampling methods can be broadly categorized as random and nonrandom.
The goal of much observational research is to identify risk factors that have a causal effect on health and social outcomes. However, observational data are subject to biases from confounding, selection and measurement, which can result in an underestimate or overestimate of the effect of interest. Various advanced statistical approaches exist that offer certain advantages in terms of addressing these potential biases. However, although these statistical approaches have different underlying statistical assumptions, in practice they cannot always completely remove key sources of bias; therefore, using design-based approaches to improve causal inference is also important. Here it is the design of the study that addresses the problem of potential bias – either by ensuring it is not present (under certain assumptions) or by comparing results across methods with different sources and direction of potential bias. The distinction between statistical and design-based approaches is not an absolute one, but it provides a framework for triangulation – the thoughtful application of multiple approaches (e.g. statistical and design based), each with their own strengths and weaknesses, and in particular sources and directions of bias. It is unlikely that any single method can provide a definite answer to a causal question, but the triangulation of evidence provided by different approaches can provide a stronger basis for causal inference. Triangulation can be considered part of wider efforts to improve the transparency and robustness of scientific research, and the wider scientific infrastructure and system of incentives.
To complement the static analysis of duty in Part I, Part II looks at the law’s leading query,“what is (the) law?” by focusing on its dynamic elements. Instead of simply mapping the law through categories, Holmes sought to develop a positioning system that took into account law’s flux. Part II expounds the central theses of The Common Law and brings to the fore the leading conceptions Holmes used to develop his notion of external standards – apperception and triangulation. It looks at how Holmes traced the development of liability from its primitive origins in revenge. Holmes sought to visualize the law’s movement through such artistic techniques as linear perspective and the creation of vanishing points. Holmes’s efforts to introduce dimensionality into law led him to emphasize the notion of the“purely legal point of view.”
Optical tracking systems typically trade off between astrometric precision and field of view. In this work, we showcase a networked approach to optical tracking using very wide field-of-view imagers that have relatively low astrometric precision on the scheduled OSIRIS-REx slingshot manoeuvre around Earth on 22 Sep 2017. As part of a trajectory designed to get OSIRIS-REx to NEO 101955 Bennu, this flyby event was viewed from 13 remote sensors spread across Australia and New Zealand to promote triangulatable observations. Each observatory in this portable network was constructed to be as lightweight and portable as possible, with hardware based off the successful design of the Desert Fireball Network. Over a 4-h collection window, we gathered 15 439 images of the night sky in the predicted direction of the OSIRIS-REx spacecraft. Using a specially developed streak detection and orbit determination data pipeline, we detected 2 090 line-of-sight observations. Our fitted orbit was determined to be within about 10 km of orbital telemetry along the observed 109 262 km length of OSIRIS-REx trajectory, and thus demonstrating the impressive capability of a networked approach to Space Surveillance and Tracking.
Dans Donald Davidson's Triangulation Argument: A Philosophical Inquiry, Robert H. Myers et Claudine Verheggen offrent une élucidation ainsi qu'une édification de l'argument de la triangulation avancé par Donald Davidson. Cet article est une introduction à un symposium consacré à leur développement de cet argument. Le symposium a débuté en 2018 en tant que table ronde réunissant les auteurs et des critiques lors du congrès annuel de l'Association canadienne de philosophie, et comprend les réponses de trois critiques, Kirk Ludwig, Alexander Miller et Paul Hurley, suivies des répliques de Verheggen et Myers. J'offre ici un bref aperçu de chacune des deux parties du livre et une esquisse des questions posées par les critiques.
In response to Paul Hurley, I argue that Donald Davidson's triangulation argument can be applied to normative beliefs only if such beliefs are answerable to properties that are at once normative and causal. The argument thus commits Davidson to a non-reductive and strikingly non-revisionary form of naturalism. In response to Kirk Ludwig, I argue that Davidson had good reason to abandon Humean accounts of pro-attitudes because he had good reason to welcome the non-reductive and non-revisionary form of naturalism that comes into view once the triangulation argument is applied to normative beliefs.
This paper is a reply to Kirk Ludwig's and Alexander Miller's comments on the first part of Donald Davidson's Triangulation Argument: A Philosophical Inquiry. It addresses concerns Ludwig expresses about the triangulation argument's success in establishing the social character of language and thought. It answers Miller's invitation to compare Davidson's non-reductionism with that of Crispin Wright, as well as the social aspect of Davidson's view with the social aspect of Saul Kripke's. And it addresses Miller's worries concerning my claims about the normativity of meaning.