Background Genuine uncertainty on superiority of one intervention over the other is called equipoise. Physician-investigators in randomized controlled trials need equipoise at least in studies with more than minimal risks. Ideally, this equipoise is also present in patient-participants. In pediatrics, data on equipoise are lacking. We hypothesize that 1) lack of equipoise at enrolment among parents may reduce recruitment; 2) lack of equipoise during participation may reduce retention in patients assigned to a less favoured treatment-strategy. Methods We compared preferences of (...) parents/patients at enrolment, documented by a questionnaire, with preferences developed during follow-up by an interview-study to investigate equipoise of child-participants and parents in the BeSt-for-Kids-study. This trial in new-onset Juvenile Idiopathic Arthritis-patients consists of three strategies. One strategy comprises initial treatment with a biological disease-modifying-antirheumatic-drug, currently not standard-of-care. Semi-structured interviews were conducted with 23 parents and 7 patients, median 11 months after enrolment. Results Initially most parents and children were not in equipoise. Parents/patients who refused participation, regularly declined due to specific preferences. Many participating families preferred the biological-first-strategy. They participated to have a chance for this initial treatment, and would even consider stopping trial-participation when not randomized for it. Their conviction of superiority of the biological-first strategy was based on knowledge from internet and close relations. According to four parents, the physician-investigator preferred the biological-first-strategy, but the majority stated that she had no preferred strategy. In phase 2, preferences tended to change to the treatment actually received. Conclusions Lack of equipoise during enrolment did not reduce study recruitment, mainly due to the fact that preferred treatment was only available within the study. Still, when developing a trial it is important to evaluate whether the physicians’ research question is in line with preferences of the patient-group. By exploring so-called ‘informed patient-group’-equipoise, successful recruitment may be enhanced and bias avoided. In our study, lack of equipoise during trial-participation did not reduce retention in those assigned to a less favoured option. We observed a change for preference towards treatment actually received, possibly explained by comparable outcomes in all three arms. (shrink)

Throughout the biological and biomedical sciences there is a growing need for, prescriptive ‘minimum information’ (MI) checklists specifying the key information to include when reporting experimental results are beginning to find favor with experimentalists, analysts, publishers and funders alike. Such checklists aim to ensure that methods, data, analyses and results are described to a level sufficient to support the unambiguous interpretation, sophisticated search, reanalysis and experimental corroboration and reuse of data sets, facilitating the extraction of maximum value from data sets (...) them. However, such ‘minimum information’ MI checklists are usually developed independently by groups working within representatives of particular biologically- or technologically-delineated domains. Consequently, an overview of the full range of checklists can be difficult to establish without intensive searching, and even tracking thetheir individual evolution of single checklists may be a non-trivial exercise. Checklists are also inevitably partially redundant when measured one against another, and where they overlap is far from straightforward. Furthermore, conflicts in scope and arbitrary decisions on wording and sub-structuring make integration difficult. This presents inhibit their use in combination. Overall, these issues present significant difficulties for the users of checklists, especially those in areas such as systems biology, who routinely combine information from multiple biological domains and technology platforms. To address all of the above, we present MIBBI (Minimum Information for Biological and Biomedical Investigations); a web-based communal resource for such checklists, designed to act as a ‘one-stop shop’ for those exploring the range of extant checklist projects, and to foster collaborative, integrative development and ultimately promote gradual integration of checklists. (shrink)

Although Archaea inhabit the human body and possess some characteristics of pathogens, there is a notable lack of pathogenic archaeal species identified to date. We hypothesize that the scarcity of disease‐causing Archaea is due, in part, to mutually‐exclusive phage and virus populations infecting Bacteria and Archaea, coupled with an association of bacterial virulence factors with phages or mobile elements. The ability of bacterial phages to infect Bacteria and then use them as a vehicle to infect eukaryotes may be difficult for (...) archaeal viruses to evolve independently. Differences in extracellular structures between Bacteria and Archaea would make adsorption of bacterial phage particles onto Archaea (i.e. horizontal transfer of virulence) exceedingly hard. If phage and virus populations are indeed exclusive to their respective host Domains, this has important implications for both the evolution of pathogens and approaches to infectious disease control. (shrink)

Provability, Computability and Reflection.

We introduce the notion of an alphabetic trace of a cut-free intuitionistic prepositional proof and show that it serves to characterize the equality of arrows in cartesian closed categories. We also show that alphabetic traces improve on the notion of the generality of proofs proposed in the literature. The main theorem of the paper yields a new and considerably simpler solution of the coherence problem for cartesian closed categories than those in [11, 14].

The Birkhoff-Maltsev problem asks for a characterization of those lattices each of which is isomorphic to the lattice L(K) of all subquasivarieties for some quasivariety K of algebraic systems. The current status of this problem, which is still open, is discussed. Various unsolved questions that are related to the Birkhoff-Maltsev problem are also considered, including ones that stem from the theory of propositional logics.

In their “social contextual view” of emotional mimicry, authors Hess and Fischer (2022) put forward emotional mimicry as a social regulator, considering it a social act, bound to certain affiliative contexts or goals. In this commentary, we argue that the core function of mimicry is to ease predicting conspecifics’ behaviours and the environment, and that as a consequence, this often smoothens social interactions. Accordingly, we make three main points. First, we argue that there is no good reason to believe that (...) the mimicry of negative expressions is fundamentally different than the mimicry of positive or ambiguous or autonomic expressions. Second, we give examples of empirical evidence that mimicry is not always a social act. Third, we show that mimicry has primary benefits for the mimicker. As such, we will briefly summarise and elaborate on the relevant findings in these respects, and propose a comparative, multi-method and ecologically valid approach which can explain the multifaceted character of the phenomenon. (shrink)

PURPOSE: To evaluate the effects of social support on comprehension and recall of consent form information in a study of Parkinson disease patients and their caregivers.DESIGN and METHODS: Comparison of comprehension and recall outcomes among participants who read and signed the consent form accompanied by a family member/friend versus those of participants who read and signed the consent form unaccompanied. Comprehension and recall of consent form information were measured at one week and one month respectively, using Part A of the (...) Quality of Informed Consent Questionnaire .RESULTS: The mean age of the sample of 143 participants was 71 years . Analysis of covariance was used to compare QuIC scores between the intervention group and control group . In the 1-week model, no statistically significant intervention effect was found . However, the intervention status by patient status interaction was statistically significant . In the 1-month model, no statistically significant intervention effect was found . Again, however, the intervention status by patient status interaction was statistically significant . At both time periods, intervention group patients scored higher on the QuIC than did intervention group caregivers, and control group patients scored lower on the QuIC than did control group caregivers.IMPLICATIONS: Social support played a significant role in enhancing comprehension and recall of consent form information among patients. (shrink)

The same research proposal was submitted to 24 district health authority (DHA) research ethics committees in different parts of the country. The objective was to obtain permission for a multi-centre research project. The study of neonatal care in different types of unit (regional, subregional and district), required that four health authorities were approached in each of six widely separated health regions in England. Data were collected and compared concerning aspects of processing, including application forms, information required, timing and decision-making. The (...) key finding was that ethics committees received and processed the applications variably, reflecting individual factors and local problems. To improve consensus and facilitate multicentre studies, standard forms and instructions are suggested and the establishment of a national committee or advisory group advocated. (shrink)

We show that the analysis of Keisler’s order can be localized to the study of φ-types. Specifically, if is a regular ultrafilter on λ such that and M is a model whose theory is countable, then is λ+-saturated iff it realizes all φ-types of size λ.

LetL(K) denote the lattice (ordered by inclusion) of quasivarieties contained in a quasivarietyK and letD 2 denote the variety of distributive (0, 1)-lattices with 2 additional nullary operations. In the present paperL(D 2) is described. As a consequence, ifM+N stands for the lattice join of the quasivarietiesM andN, then minimal quasivarietiesV 0,V 1, andV 2 are given each of which is generated by a 2-element algebra and such that the latticeL(V 0+V1), though infinite, still admits an easy and nice description (...) (see Figure 2) while the latticeL(V 0+V1+V2), because of its intricate inner structure, does not. In particular, it is shown thatL(V 0+V1+V2) contains as a sublattice the ideal lattice of a free lattice with free generators. Each of the quasivarietiesV 0,V 1, andV 2 is generated by a 2-element algebra inD 2. (shrink)

Let T 1 , T 2 be countable first-order theories, M i ⊨ T i , and ������ any regular ultrafilter on λ ≥ $\aleph_{0}$ . A longstanding open problem of Keisler asks when T 2 is more complex than T 1 , as measured by the fact that for any such λ, ������, if the ultrapower (M 2 ) λ /������ realizes all types over sets of size ≤ λ, then so must the ultrapower (M 1 ) λ /������. (...) In this paper, building on the author's prior work [12] [13] [14], we show that the relative complexity of first-order theories in Keisler's sense is reflected in the relative graph-theoretic complexity of sequences of hypergraphs associated to formulas of the theory. After reviewing prior work on Keisler's order, we present the new construction in the context of ultrapowers, give various applications to the open question of the unstable classification, and investigate the interaction between theories and regularizing sets. We show that there is a minimum unstable theory, a minimum TP 2 theory, and that maximality is implied by the density of certain graph edges (between components arising from Szemerédi-regular decompositions) remaining bounded away from 0, 1. We also introduce and discuss flexible ultrafilters, a relevant class of regular ultrafilters which reflect the sensitivity of certain unstable (non low) theories to the sizes of regularizing sets, and prove that any ultrafilter which saturates the minimal TP 2 theory is flexible. (shrink)

Synaesthesia is a condition in which one type of stimulation evokes the sensation of another, as when the hearing of a sound produces photisms, i.e. mental percepts of colours. R is a 20 year old colour blind subject who, in addition to the relatively common grapheme-colour synaesthesia, presents a rarely reported cross modal perception in which a variety of visual stimuli elicit aura-like percepts of colour. In R, photisms seem to be closely related to the affective valence of stimuli and (...) typically bring out a consistent pattern of emotional responses. The present case study suggests that colours might be an intrinsic category of the human brain. We developed an empirical methodology that allowed us to study the subject's otherwise inaccessible phenomenological experience. First, we found that R shows a Stroop effect elicited by photisms despite the fact that he does not show a regular Stroop with real colours. Secondly, by manipulating the colour context we confirmed that colours can alter R's emotional evaluation of the stimuli. Furthermore, we demonstrated that R's auras may actually lead to a partially inverted emotional spectrum where certain stimuli bring out emotional reactions opposite to the normal ones. These findings can only be accounted for by considering R's subjective colour experience or qualia. Therefore the present paper defends the view that qualia are a useful scientific concept that can be approached and studied by experimental methods. (shrink)

A comprehensive, critical evaluation of the ideas of the Italian philosopher Benedetto Croce, including a summary of his life.

Paperback. The book treats two general questions: 1. Whether Erasmanism and Erasmian Humanism existed as a recognizable attitude during the sixteenth and early seventeenth centuries; 2. Whether Erasminism represented a definable middle way between the confessional conflicts of these times. How important was Erasmanism in these respects? The treatment of these two questions is geographically limited to those countries where Erasmus himself was active: Italy, The Netherlands, Holy Roman Empire, Switzerland and England.Erasmanism as a concept has hardly been studied before, (...) although the term is used freely by scholars of the early modern period. This book is a first attempt at a begriffsgeschichte of Erasminism. (shrink)

Since the 1930s, scientists studying the neurological disease scrapie had assumed that the infectious agent was a virus. By the mid 1960s, however, several unconventional properties had arisen that were difficult to reconcile with the standard viral model. Evidence for nucleic acid within the pathogen was lacking, and some researchers considered the possibility that the infectious agent consisted solely of protein. In 1982, Stanley Prusiner coined the term `prion' to emphasize the agent's proteinaceous nature. This infectious protein hypothesis was denounced (...) by many scientists as `heretical'.This essay asks why the concept of an infectious protein was considered controversial. Some biologists justified their evaluation of this hypothesis on the grounds that an infectious protein contradicted the `central dogma of molecular biology'. Others referred to vague theoretical constraints such as molecular biology's `theoretical structure' or `framework'. Examination of the objections raised by researchers reveals exactly what generalizations were being challenged by a protein model of infection.This two-part survey of scrapie and prion research reaches several conclusions: (1) A theoretical framework is present in molecular biology, exerting its influence in hypothesis formation and evaluation; (2) This framework consists of several related, yet separable, generalizations or `elements', including Francis Crick's Central Dogma and Sequence Hypothesis, plus notions concerning infection, replication, protein synthesis, and protein folding; (3) The term `central dogma' has stretched beyond Crick's original 1958 definition to encompass at least two other `framework elements': replication and protein synthesis; and (4) From the study of scrapie and related diseases, biological information has been delineated into at least two classes: sequential and what I call `conformational'.In Part I of this essay, a brief review of the central dogma, as outlined by both Francis Crick and James Watson, will be given. The developments in scrapie research from 1965 to 1972 will then be traced. This section will summarize many of the puzzling, non-viral-like properties of the scrapie agent. Alternative hypotheses to the viral explanation will also be presented, including early versions of a protein-only hypothesis. Part II of this essay will follow the developments in scrapie and prion research from the mid 1970s through 1991. The growing prominence of a protein-only model of infection will be balanced by continued objections from many researchers to a pathogen devoid of nucleic acid. These objections will help illuminate those generalizations in molecular biology that were indeed challenged by a protein-only model of infection. (shrink)