In this paper, I will argue that, while the ethical issues raised by cluster randomization can be challenging, they are not new. My thesis divides neatly into two parts. In the first, easier part I argue that many of the ethical challenges posed by cluster randomized human subjects research are clearly present in other types of human subjects research, and so are not novel. In the second, more difficult part I discuss the thorniest ethical challenge for (...) class='Hi'>cluster randomized research – cases where consent is genuinely impractical to obtain. I argue that once again these cases require no new analytic insight; instead, we should look to political philosophy for guidance. In other words, the most serious ethical problem that arises in cluster randomized research also arises in political philosophy. (shrink)

Randomized controlled trials sometimes test interventions that aim to improve existing services targeted to a subset of individuals identified after randomization. Accordingly, the treatment could affect the composition of service recipients and the offered services. With such bias, intention-to-treat estimates using data on service recipients and nonrecipients may be difficult to interpret. This article develops causal estimands and inverse probability weighting estimators for complier populations in these settings, using a generalized estimating equation approach that adjusts the standard errors for (...) estimation error in the IPW weights. While our focus is on more general clustered RCTs, the methods also apply to nonclustered RCTs. Simulations show that the estimators achieve nominal confidence interval coverage under the assumed identification conditions. An empirical application demonstrates the methods using data from a large-scale RCT testing the effects of early childhood services on children’s cognitive development scores. An R program for estimation is available for download. (shrink)

The recent Ebola virus disease outbreak in Western African countries has raised questions regarding the feasibility of adopting conventional trial designs such as randomized controlled trials for conducting experimental trials in the midst of a fatal epidemic. In the context of Ebola ça Suffit trial conducted in Guinea for testing the efficacy and effectiveness of rVSV–ZEBOV, a candidate vaccine, I argue that the trial design and the methodologies adopted for the trial have been rightly chosen for their ethical appropriateness and (...) social utilities rather than only epistemic advantages. In this paper, I propose and defend the view that in varying scientific research contexts, it is entirely legitimate that non-epistemic values may be prioritized over epistemic considerations. Two vital methodological choices scientists should make while designing a clinical trial are: the choice of appropriate control group and the choice of appropriate randomization. Given this background, I show that the choice of delayed vaccination arm as the control group over placebo control group and the choice of cluster randomization over individually controlled randomization for conducting Ebola ça Suffit trial are perfect instances of such a scenario where addressing social and ethical issues have been justifiably prioritized over epistemic values so that the research in a specific scientific context could be conducted in a socially relevant manner. (shrink)

Randomized controlled trials in educational research tend to be small. Small trials can have large, chance, imbalances in important covariates. For studies with sample sizes greater than 50, chance imbalances can be corrected using analysis of covariance; for small trials, however, statistical power is maximized if the trial is balanced and analysis of covariance is used in the analysis. The aim of the present study was to discuss methods of improving covariate balance in trial design and to demonstrate the method (...) of minimization. Using an exemplar of a cluster or class‐randomized trial with 29 classes, we employed minimization to achieve covariate balance. Minimization achieved good balance on four prognostic variables. Many trialists in education use restricted forms of allocation, including pairing or stratified randomization. These approaches have disadvantages. Another approach rarely used in educational research is minimization. Minimization uses a simple arithmetic algorithm to produce balanced groups across a number of important covariates and should be more widely used in educational and psychological research. (shrink)

ObjectiveOverweight and obesity [body mass index ≥ 25 kg/m2] are associated with poorer prognosis among women with breast cancer, and weight gain is common during treatment. Symptoms of depression and anxiety are also highly prevalent in women with breast cancer and may be exacerbated by post-diagnosis weight gain. Altered brain function may underlie psychological distress. Thus, this secondary analysis examined the relationship between BMI, psychological health, and resting state functional connectivity among women with breast cancer.MethodsThe sample included 34 post-menopausal women (...) newly diagnosed with Stage 0-IIa breast cancer who were enrolled in a 6-month randomized controlled trial of aerobic exercise vs. usual care. At baseline prior to randomization, whole-brain analyses were conducted to evaluate the relationship between BMI and seed-to-voxel rsFC of the hippocampus and amygdala. Connectivity values from significant clusters were then extracted and examined as predictors of self-reported depression and anxiety.ResultsMean BMI was in the obese range. For both seeds examined, higher BMI was associated with lower rsFC with regions of prefrontal cortex, including ventrolateral PFC, dorsolateral PFC, and superior frontal gyrus. Hippocampal connectivity with the vlPFC was negatively correlated with self-reported anxiety.ConclusionHigher BMI was associated with lower hippocampal and amygdala connectivity to regions of PFC implicated in cognitive control and emotion regulation. BMI-related differences in hippocampal and amygdala connectivity following a recent breast cancer diagnosis may relate to future worsening of psychological functioning during treatment and remission. Additional longitudinal research exploring this hypothesis is warranted. (shrink)

We have been asked to consider the feasibility of piloting a Citizens’ Basic Income : a basic, unconditional, universal, individual, regular payment that would replace aspects of social security and be introduced alongside changes to taxes. Piloting and evaluating a CBI as a Cluster Randomized Control Trial raises the question of whether intervention and comparison groups would be in equipoise, and thus whether randomization would be ethical. We believe that most researchers would accept that additional income, or reduced (...) conditions on receiving income would be likely to improve health, especially at lower income levels. However, there are genuine uncertainties about the impacts on other outcomes, and CBI as a mechanism of providing income. There is also less consensus amongst civil servants and politicians about the impacts on health, and substantial disagreement about whether these would outweigh other impacts. We believe that an RCT is ethical because of these uncertainties. We also argue that the principle of equipoise should apply to randomized and non-randomized trials; that randomization is a fairer means of allocating to intervention and comparison groups; and that there is an ethical case for experimentation to generate higher-quality evidence for policymaking that may otherwise do harm. (shrink)

ObjectivesTo describe reporting of informed consent in pragmatic trials, justifications for waivers of consent and reporting of alternative approaches to standard written consent. To identify factors associated with (1) not reporting and (2) not obtaining consent.MethodsSurvey of primary trial reports, published 2014–2019, identified using an electronic search filter for pragmatic trials implemented in MEDLINE, and registered in ClinicalTrials.gov.ResultsAmong 1988 trials, 132 (6.6%) did not include a statement about participant consent, 1691 (85.0%) reported consent had been obtained, 139 (7.0%) reported a (...) waiver and 26 (1.3%) reported consent for one aspect (eg, data collection) but a waiver for another (eg, intervention). Of the 165 trials reporting a waiver, 76 (46.1%) provided a justification. Few (53, 2.9%) explicitly reported use of alternative approaches to consent. In multivariable logistic regression analyses, lower journal impact factor (p=0.001) and cluster randomisation (p<0.0001) were significantly associated with not reporting on consent, while trial recency, cluster randomisation, higher-income country settings, health services research and explicit labelling as pragmatic were significantly associated with not obtaining consent (all p<0.0001).DiscussionNot obtaining consent seems to be increasing and is associated with the use of cluster randomisation and pragmatic aims, but neither cluster randomisation nor pragmatism are currently accepted justifications for waivers of consent. Rather than considering either standard written informed consent or waivers of consent, researchers and research ethics committees could consider alternative consent approaches that may facilitate the conduct of pragmatic trials while preserving patient autonomy and the public’s trust in research. (shrink)

In clinical and agricultural trials, there is the danger that an experimental outcome appears to arise from the causal process or treatment one is interested in when, in reality, it was produced by some extraneous variation in the experimental conditions. The remedy prescribed by classical statisticians involves the procedure of randomization, whose effectiveness and appropriateness is criticized. An alternative, Bayesian analysis of experimental design, is shown, on the other hand, to provide a coherent and intuitively satisfactory solution to the (...) problem. (shrink)

Randomization procedures are used in legal and statistical applications, aiming to shield important decisions from spurious influences. This article gives an intuitive introduction to randomization and examines some intended consequences of its use related to truthful statistical inference and fair legal judgment. This article also presents an open-code Java implementation for a cryptographically secure, statistically reliable, transparent, traceable, and fully auditable randomization tool.

In the recent literature across philosophy, medicine and public health policy, many influential arguments have been put forward to support the use of randomization procedures to allocate scarce life-saving resources. In this paper, I provide a systematic categorization and a critical evaluation of these arguments. I shall argue that those arguments justify using RAND to allocate SLSR in fewer cases than their proponents maintain and that the relevant decision-makers should typically allocate SLSR directly to the individuals with the strongest (...) claims to these resources rather than use RAND to allocate such resources. (shrink)

Batteries are a fundamental storage component due to its various applications in mobility, renewable energies and consumer electronics among others. Regardless of the battery typology, one key variable from a user’s perspective is the remaining energy in the battery. It is usually presented as the percentage of remaining energy compared to the total energy that can be stored and is labeled State Of Charge (SOC). This work addresses the development of a hybrid model based on a Lithium Iron Phosphate (LiFePO4) (...) power cell, due to its broad implementation. The proposed model calculates the SOC, by means of voltage and electric current as inputs and the latter as the output. Therefore, four models based on k-Means, Agglomerative Clustering, Gaussian Mixture and Spectral Clustering techniques have been tested in order to obtain an optimal solution. (shrink)

Why do classic biostatistical studies, alleged to provide causal explanations of effects, often fail? This article argues that in statistics-relevant areas of biology—such as epidemiology, population biology, toxicology, and vector ecology—scientists often misunderstand epistemic constraints on use of the statistical-significance rule (SSR). As a result, biologists often make faulty causal inferences. The paper (1) provides several examples of faulty causal inferences that rely on tests of statistical significance; (2) uncovers the flawed theoretical assumptions, especially those related to randomization, that (...) likely contribute to flawed biostatistics; (3) re-assesses the three classic (SSR-warrant, avoiding-selection-bias, and avoiding-confounders) arguments for using SSR only with randomization; and (4) offers five new reasons for biologists to use SSR only with randomized experiments. (shrink)

Researchers may be concurrently recruiting for several multi-site clinical trials at the same time, placing them in the position of potentially recruiting a patient-participant into one of several competing trials. This article examines how researchers should go about making equipoise calculations when competition emerges, creating ethical dilemmas about randomizing among, and not merely within, clinical trials.

This article attempts to comprehend the problem within the methodology of science. The authors compare the concepts of creativity and heuristics and suggest a semantic differentiation between them, and also offer their own viewpoint on the main types of activity corresponding to these concepts. The problem of creativity is associated with the characteristics that a person must have in order to solve tasks and problems. The authors consider the relationship between the problem and the task, as well as some major (...) techniques to tackle them. Here they substantiate the idea of a wider adaptation of randomization as a special tactic, that is, going beyond the narrow framework of mathematical statistics and empirical research. In this context, the authors introduce the notion of “epistemological randomization”, designed to denote the following of open rationality without abandoning the rational way of solving scientific problems. This technique is viewed as a phenomenon related to the counterfactual thinking. The last part of the article proposes a typology of personalities as problem and task solvers – adaptive, heuristic and creative personalities. It is assumed that the “heuristic” personality aims to complete tasks, which, unlike problems, have a final solution, while the “creative” personality aims to expand the problem field. The latter type is characterized as capable and inclined to use the “epistemological randomization”, the techniques of lateral thinking and other techniques that suggest several methods of solving problems and tasks at once. (shrink)

Companies' urge to maximise their profits and their attempts to remain in the highly competitive globalised market gave birth to the TQM concept and have kept it alive. TQM is a comprehensive look which encompasses virtually every aspect of the value chain as well as the human resource and customer satisfaction. Therefore, a great number of companies feel obliged to implement its rules, and procedures. However, the concept is rather complicated and culture-bound, and calls for further research in new settings. (...) The aim of this study is to examine the influences of critical success factors of TQM on customer focus therefore, employees are classified based on their perceptions from critical success factors of total quality management and consequently the level of customer focus is compared between the different classifications. The findings reveal that there is significant difference on the level of the customer focus between the established groups of employees. (shrink)

Peter Urbach has argued, on Bayesian grounds, that experimental randomization serves no useful purpose in testing causal hypothesis. I maintain that he fails to distinguish general issues of statistical inference from specific problems involved in identifying causes. I concede the general Bayesian thesis that random sampling is inessential to sound statistical inference. But experimental randomization is a different matter, and often plays an essential role in our route to causal conclusions.

Decoupling is a general principle that allows us to separate simple components in a complex system. In statistics, decoupling is often expressed as independence, no association, or zero covariance relations. These relations are sharp statistical hypotheses, that can be tested using the FBST - Full Bayesian Significance Test. Decoupling relations can also be introduced by some techniques of Design of Statistical Experiments, DSEs, like randomization. This article discusses the concepts of decoupling, randomization and sparsely connected statistical models in (...) the epistemological framework of cognitive constructivism. (shrink)

While the HVTN 505 trial showed no overall efficacy of the tested vaccine to prevent HIV infection over placebo, markers measuring immune response to vaccination were strongly correlated with infection. This finding generated the hypothesis that some marker-defined vaccinated subgroups were partially protected whereas others had their risk increased. This hypothesis can be assessed using the principal stratification framework (Frangakis and Rubin, 2002) for studying treatment effect modification by an intermediate response variable, using methods in the sub-field of principal surrogate (...) (PS) analysis that studies multiple principal strata. Unfortunately, available methods for PS analysis require an augmented study design not available in HVTN 505, and make untestable structural risk assumptions, motivating a need for more robust PS methods. Fortunately, another sub-field of principal stratification, survivor average causal effect (SACE) analysis (Rubin, 2006) – which studies effects in a single principal stratum – provides many methods not requiring an augmented design and making fewer assumptions. We show how, for a binary intermediate response variable, methods developed for SACE analysis can be adapted to PS analysis, providing new and more robust PS methods. Application to HVTN 505 supports that the vaccine partially protected individuals with vaccine-induced T-cells expressing certain combinations of functions. (shrink)

Randomization is an integral part of well-designed statistical trials, and is also a required procedure in legal systems. Implementation of honest, unbiased, understandable, secure, traceable, auditable and collusion resistant randomization procedures is a mater of great legal, social and political importance. Given the juridical and social importance of randomization, it is important to develop procedures in full compliance with the following desiderata: (a) Statistical soundness and computational efficiency; (b) Procedural, cryptographical and computational security; (c) Complete auditability and (...) traceability; (d) Any attempt by participating parties or coalitions to spuriously influence the procedure should be either unsuccessful or be detected; (e) Open-source programming; (f) Multiple hardware platform and operating system implementation; (g) User friendliness and transparency; (h) Flexibility and adaptability for the needs and requirements of multiple application areas (like, for example, clinical trials, selection of jury or judges in legal proceedings, and draft lotteries). This paper presents a simple and easy to implement randomization protocol that assures, in a formal mathematical setting, full compliance to the aforementioned desiderata for randomization procedures. (shrink)

Governments are increasingly using randomized controlled trials (RCTs) to evaluate policy interventions. RCTs are often understood to provide the highest quality evidence regarding the causal efficacy of an intervention. While randomization plays an essential epistemic role in the context of policy RCTs however, it also plays an important distributive role. By randomly assigning participants to either the intervention or control arm of an RCT, people are subject to different policies and so, often, to different types and levels of benefits. (...) In this paper, I identify one necessary condition as well as a set of sufficient conditions for the permissible use of random assignment by government agencies. I argue first that random assignment is permissible only if it is consistent with governments’ duty to realize morally important outcomes. I argue second that random assignment is permissible in cases where investigators are in a state of genuine equipoise regarding all arms of the experiment and the policy to which people have a claim of justice. Finally, I defend a set of conditions under which random assignment is permissible in cases where one or more arms of a policy RCT are reasonably expected to be either superior or inferior to this policy. (shrink)

Berys Gaut has recently defended a cluster account of art. He proposes it as superior to other anti-essentialist positions. I argue that his defence of this claim is unconvincing. Not only is the cluster theory consistent with the current crop of disjunctive definitions, it is at its most plausible when seen in such terms.

Noah Rosenberg et al.'s 2002 article “Genetic Structure of Human Populations” reported that multivariate genomic analysis of a large cell line panel yielded reproducible groupings (clusters) suggestive of individuals' geographical origins. The paper has been repeatedly cited as evidence that traditional notions of race have a biological basis, a claim its authors do not make. Critics of this misinterpretation have often suggested that it follows from interpreters' personal biases skewing the reception of an objective piece of scientific writing. I contend, (...) however, that the article itself to some degree facilitates this misrepresentation. I analyze in detail several verbal and visual features of the original article that may predispose aspects of its racial interpretation; and, tracing the arguments of one philosopher and one popular science writer, I show how these features are absorbed, transformed into arguments for a biological basis of race, and re-attributed to the original. The essay demonstrates how even slight ambiguities can enable the misappropriation of scientific writing, unintentionally undermining the authors' stated circumspection on the relationship between cluster and race. (shrink)

The cluster account, one of the best attempts at art classification, is guilty of ahistoricism. While cluster theorists may be happy to limit themselves to accounting for what art is now rather than how the term was understood in the past, they cannot ignore the fact that people seem to apply different clusters when judging art from different times. This paper shows that while allowing for this kind of historical relativity may be necessary to save the account, doing (...) so could result in incorporating an essentially institutional component or making the theory extremely complex and virtually impossible to use. (shrink)

A recent concern in the debate on corporate social responsibility (CSR) in developing countries relates to the tension between demands for CSR compliance found in many global value chains (GVCs) and the search for locally appropriate responses to these pressures. In this context, an emerging and relatively understudied area of interest relates to small firm industrial clusters. Local clusters offer the potential for local joint action, and thus a basis for improving local compliance on CSR through collective monitoring and local (...) governance. This article explores the interrelationship between global governance, exercised through GVC ties, and local governance, via cluster institutions, in ensuring compliance with CSR pressures. It undertakes a comparative analysis of two leading export-oriented football manufacturing clusters in South Asia that have both faced common challenges on child labour. The article shows that both forms vertical and horizontal governance have played a part in shaping the response of the two clusters on child labour. Moreover, these two distinct forms of governance have also led to quite differentiated outcomes in terms of forms of work organization and child labour monitoring. This raises broader questions on how global CSR demands can locally be better embedded and the conditions under which football stitchers labour in these new work forms. (shrink)

This study focused on the identification problems of two-input single-output system with moving average noises based on unsupervised learning methods applied to the input signals. The input signal to the autoregressive moving average model is proposed to be arriving from a source with continuous technical and environmental changes as two separate featured input signals. These two input signals were grouped in a number of clusters using the K-means clustering algorithm. The clustered input signals were supplied to the model in an (...) orderly fashion from cluster-1 up to cluster-K. To ensure that the output signal can be best predicted from the input signal which in turn leads to selecting good enough model for its intended use, the magnitude-squared coherence measure is applied to the input/output signals in the cases of clustered and nonclustered inputs, which indicates best correlation coefficient when measured with clustered inputs. From collected input-output signals, we deduce a K-means clustering based recursive least squares method for estimating the parameter of autoregressive moving average system. The simulation results indicate that the suggested method is effective. (shrink)

The nature of the process of meaning-making in science has been one of the central problems in the philosophy of science of the 20th century. Yet, in spite of strenuous efforts by many able philosophers and historians of science over the past three decades or so, our understanding of this process continues to be unsatisfactory and fragmented at best. The need for an adequate account has been particularly exacerbated by the "infamous" and often misinterpreted problem of incommensurability , and its (...) alleged consequence, the incomparability of scientific theories--which presumably threatens the rationality, objectivity, and progress of science. ;In this project, I argue that a new and revised cluster theory can be articulated, which meets the objections typically raised against traditional theories of meaning and theories of reference . Such a theory is not only based on more plausible assumptions and principles, but, in addition, it satisfies the main adequacy requirements formulated by proponents of a "cognitive-historical approach" . I am thus concerned not just with refuting "the entering wedge" of the argument against a defense of cluster theory, but with offering a relatively developed theory, sufficiently fleshed out to permit appreciation of its distinctiveness and evaluation of its merits. ;I argue that the new cluster theory provides not only an adequate account of the process of meaning-making in science, but also a nuanced and context-sensitive one, which exhibits the fine-structure of the history of science. It is thus capable of accounting for the different kinds and degrees of meaning and reference changes in science. Furthermore, when applied in a case-study of the "chemical revolution," it accounts for that which has escaped change without discontinuity, or even, as result of a broader framework of continuous conceptual change. The new cluster theory constitutes a proposal showing how the comparability of scientific theories is possible, how we have in fact been comparing them all along, despite "local incommensurabilities" of various kinds and degrees. Such a theory offers new insights into the developments of the chemical revolution in particular, but also into the structure and process of scientific revolutions in general. In short, it gives us a new framework for understanding the rationality, objectivity, and progress of science. (shrink)

Outcome-adaptive randomization has been proposed as a corrective to certain ethical difficulties inherent in the traditional randomized clinical trial using fixed-ratio randomization. In particular, it has been suggested that OAR redresses the balance between individual and collective ethics in favour of the former. In this paper, I examine issues of welfare and autonomy arising in relation to OAR. A central issue in discussions of welfare in OAR is equipoise, and the moral status of OAR is crucially influenced by (...) the way in which this concept is construed. If OAR is based on a model of equipoise that demands strict indifference between competing interventions throughout the trial, such equipoise is disturbed by accruing data favouring one treatment over another; OAR seeks to redress this by weighting randomization to the seemingly superior treatment. However, this is a partial response, as patients continue to be allocated to the inferior therapy. Moreover, it rests upon considerations of aggregate harms and benefits, and does not therefore uphold individual ethics. Issues of fairness also arise, as early and late enrollees are randomized on a different basis. Fixed-ratio randomization represents a fuller and more consistent response to a loss of equipoise, as so construed. With regard to consent, the complexity of OAR poses challenges to adequate disclosure and comprehension. Additionally, OAR does not offer a remedy to the therapeutic misconception—participants’ tendency to attribute treatment allocation in an RCT to individual clinical judgments, rather than to scientific considerations—and, if anything, accentuates rather than alleviates this misconception. In relation to these issues, OAR fails to offer ethical advantages over fixed-ratio randomization. More broadly, the ethical basis of OAR can be seen to lie more in collective than in individual ethics, and overall it fares worse in this territory than fixed-ratio randomization. (shrink)

A dominant strand of philosophical thought holds that natural kinds are clusters of objects with shared properties. Cluster theories of natural kinds are often taken to be a late twentieth-century development, prompted by dissatisfaction with essentialism in philosophy of biology. I will argue here, however, that a cluster theory of kinds had actually been formulated by William Whewell (1794-1866) more than a century earlier. Cluster theories of kinds can be characterized in terms of three central commitments, all (...) of which are present in Whewell’s work on classification. Like contemporary cluster theorists, Whewell claims that kinds are united by similarity, that many kinds do not have essences, and that there are “gaps” between kinds. Moreover, Whewell advises taxonomists to look for consilience (roughly, convergence) between different classificatory schemes, a recommendation that reinforces the identification of natural classes with property clusters. Thus Whewell was not only an early cluster theorist, but one with important insights into what a cluster theory of kinds means for the practice of classification. (shrink)

Regier, Kay, and Khetarpal report the results of computer simulations that cluster color stimuli on the basis of their coordinates in CIELAB space, one of two commonly used perceptual color spaces. Regier and coauthors find partitions of those stimuli that are strikingly similar to the way actual color lexicons partition color space. They do not argue for the custom-made clustering method used in their simulations, nor for the assumption of CIELAB space. The present paper aims to answer the question (...) to what extent their computational results depend on these assumptions. It does this by applying a great variety of known clustering methods to Regier et al.’s stimuli, and by assuming not only CIELAB space but also CIELUV space, the other main color space. (shrink)

In standard medical care, physicians select treatments for patients based on clinical judgment, considering which treatment is best for the individual patient, given the patient's history and circumstances. In contrast, investigators conducting randomized clinical trials select treatments for participants based on a random selection process. Because this process represents a significant departure from the norms of standard medical care, it is widely assumed that potential research participants must understand randomization to give valid informed consent. This assumption, together with data (...) that many research participants do not understand randomization, implies that randomized clinical trials often fail to obtain adequately informed consent. Before accepting this conclusion, and before initiating extensive efforts to improve research participants' understanding of randomization, we should assess the plausible, but rarely analyzed assumption that participants need to understand randomization to give valid informed consent for randomized clinical trials. (shrink)

This paper replies to objections from Thomas Adajian, Stephen Davies, and Robert Stecker to my claim, defended in ‘"Art" as a Cluster Concept’, that ‘art’ is a cluster concept and so cannot be defined. The paper also clarifies and extends the arguments of the earlier paper and locates its position in relation to the work of Morris Weitz.

The gain of a selective advantage in cancer as well as the establishment of complex traits during evolution require multiple genetic alterations, but how these mutations accumulate over time is currently unclear. There is increasing evidence that a mutator phenotype perpetuates the development of many human cancers. While in some cases the increased mutation rate is the result of a genetic disruption of DNA repair and replication or environmental exposures, other evidence suggests that endogenous DNA damage induced by AID/APOBEC cytidine (...) deaminases can result in transient localized hypermutation generating simultaneous, closely spaced (i.e. “clustered”) multiple mutations. Here, we discuss mechanisms that lead to mutation cluster formation, the biological consequences of their formation in cancer and evidence suggesting that APOBEC mutagenesis can also occur genome‐wide. This raises the possibility that dysregulation of these enzymes may enable rapid malignant transformation by increasing mutation rates without the loss of fitness associated with permanent mutators. (shrink)

Our prominent definitions of cognition are too vague and lack empirical grounding. They have not kept up with recent developments, and cannot bear the weight placed on them across many different debates. I here articulate and defend a more adequate theory. On this theory, behaviors under the control of cognition tend to display a cluster of characteristic properties, a cluster which tends to be absent from behaviors produced by non-cognitive processes. This cluster is reverse-engineered from the empirical (...) tests that comparative psychologists use to determine whether a behavior was generated by a cognitive or a non-cognitive process. Cognition should be understood as the natural kind of psychological process that non-accidentally exhibits the properties assessed by these tests (as well as others we have not yet discovered). Finally, I review two plausible neural accounts of cognition's underlying mechanisms?one based in localization of function to particular brain regions and another based in the more recent distributed networks approach to neuroscience?which would explain why these properties non-accidentally cluster. While this notion of cognition may be useful for a number of debates, I here focus on its application to a recent crisis over the distinction between cognition and association in comparative psychology. (shrink)

ABSTRACT: The cluster theory of names is generally thought to have been to have been utterly discredited by the objections raised against it by Kripke in Naming and Necessity. In this paper, I develop a new version of the cluster theory in which the role played by clusters of associated descriptions is occupied by teams of cognitive relations. And I argue that these teams of relations find a home in an account of the meanings of expressions in epistemic (...) sentence frames, and in a more general theory of the reference of proper names. RÉSUMÉ: La théorie des faisceaux de noms est généralement considérée sans fondement depuis les objections soulevées par Kripke dans Naming and Necessity. Nous proposons une nouvelle version de la théorie des faisceaux dans laquelle le rôle joué par les faisceaux de descriptions associées est pris en charge par des équipes de relations cognitives. Ces équipes de relations trouvent leur place au sein de l’explication de la signification des expressions dans le cadre de phrases épistémologiques et, plus généralement, dans celui d’une théorie de la référence des noms propres. (shrink)

Individuals with trypophobia have an aversion towards clusters of roughly circular shapes, such as those on a sponge or the bubbles on a cup of coffee. It is unclear why the condition exists, given the harmless nature of typical eliciting stimuli. We suggest that aversion to clusters is an evolutionarily prepared response towards a class of stimuli that resemble cues to the presence of parasites and infectious disease. Trypophobia may be an exaggerated and overgeneralised version of this normally adaptive response. (...) Consistent with this explanation, individuals with trypophobia, as well as comparison individuals, reported aversion towards disease-relevant cluster stimuli, but only the trypophobic group reported aversion towards objectively harmless cluster stimuli that had no relevance to disease. For both groups the level of aversion reported was predicted uniquely by a measure of disgust sensitivity. Scaled emotion ratings and open-ended responses revealed that the aversive response was predominantly based on the disease avoidance emotion, disgust. Many open-ended responses also described skin sensations. These findings support the proposal that individuals with trypophobia primarily perceive cluster stimuli as cues to ectoparasites and skin-transmitted pathogens. (shrink)