Vleeskens, F. D. A. Spinoza en zijn tijd.--Klever, W. N. A. Ervaring en rede.--Petry, M. J. De Regenboog.--Bend, J. G. van der. Spinoza's liberale rechtsstaat.--Sperna Weiland, J. Vrijheid.

BackgroundIn the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies.MethodsBetween 2013 and 2019, 8252 participants (...) (mean age 58 ± 9 years, 54% women) were recruited with a follow-up questionnaire administered to 909 participants (40% response rate) at 1-year. The CAHHM policy followed a restricted approach, whereby routine feedback on IFs was not provided. Only IFs of severe structural abnormalities were reported.ResultsSevere structural abnormalities occurred in 8.3% (95% confidence interval 7.7–8.9%) of participants, with the highest proportions found in the brain (4.2%) and abdomen (3.1%). The majority of participants (97%) informed of an IF reported no change in quality of life, with 3% of participants reporting that the knowledge of an IF negatively impacted their quality of life. Furthermore, 50% reported increased stress in learning about an IF, and in 95%, the discovery of an IF did not adversely impact his/her life insurance policy. Most participants (90%) would enrol in the study again and perceived the MRI scan to be beneficial, regardless of whether they were informed of IFs. While the implications of a restricted approach to IF management was perceived to be mostly positive, a degree of diagnostic misconception was present amongst participants, indicating the importance of a more thorough consent process to support participant autonomy.ConclusionThe management of IFs from research MRI scans remain a challenging issue, as participants may experience stress and a reduced quality of life when IFs are disclosed. The restricted approach to IF management in CAHHM demonstrated a fair fulfillment of the overarching ethical principles of respect for autonomy, concern for wellbeing, and justice. The approach outlined in the CAHHM policy may serve as a framework for future research studies.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/nct02220582. (shrink)

Objectives To evaluate whether the requirement of “minimal risk and burden” for paediatric research without direct benefit to the subjects compromises the ability to obtain data necessary for improving paediatric care. To provide evidence-based reflections on the EU recommendation that allows for a higher level of risk. Design and setting Systematic analysis of the approval/rejection decisions made by the Dutch Central Committee on Research involving Human Subjects (CCMO). Review methods The analysis included 165 proposals for paediatric research without direct benefit (...) that were reviewed by the CCMO between January, 2000, and July, 2007. A separate, in-depth analysis of all drug studies included 18 early phase drug studies and nine other drug studies without direct benefit. Results 11 out of 165 studies were definitively rejected because the CCMO did not regard the risk and/or burden to be minimal. In three of these 11 cases (including two early phase drug studies) the requirement of minimal risk and burden was cited as the only reason for rejection. Four other early phase drug studies also involved risks and/or burdens that were not regarded to be minimal but were nevertheless approved. Conclusions The requirement of minimal risk and burden, aiming to protect research subjects, occasionally leads to rejection of protocols. Early phase drug studies relatively often do not comply with the requirement. Committees may find ways to approve important studies that formally should be rejected, but that is not a desirable solution. The regulatory framework should be revised to make such occasional exceptions to the requirement legitimate and transparent. (shrink)

Context. The identification of the sources that reionized the Universe and their specific contribution to this process are key missing pieces of our knowledge of the early Universe. Faint star-forming galaxies may be the main contributors to the ionizing photon budget during the epoch of reionization, but their escaping photons cannot be detected directly due to inter-galactic medium opacity. Hence, it is essential to characterize the properties of faint galaxies with significant Lyman continuum photon leakage up to z 4 to (...) define indirect indicators allowing analogues to be found at the highest redshift. Aims. Long gamma-ray bursts explode typically in star-forming regions of faint, star-forming galaxies. Through LGRB afterglow spectroscopy it is possible to detect directly LyC photons. Our aim is to use LGRBs as tools to study LyC leakage from faint, star-forming galaxies at high redshift. Methods. Here we present the observations of LyC emission in the afterglow spectra of GRB 191004B at z = 3:5055, together with those of the other two previously known LyC-emitting LGRB, to determine their LyC escape fraction and compare their properties. Results. From the afterglow spectrum of GRB 191004B we determine a neutral hydrogen column density at the LGRB redshift of og =17:2 0:15, and negligible extinction. The only metal absorption lines detected are C iv and Si iv. In contrast to GRB 050908 and GRB 060607A, the host galaxy of GRB 191004B displays significant Ly emission. From its Ly emission and the non-detection of Balmer emission lines we constrain its star-formation rate to 1 SFR 4:7 M yr. 1. We fit the Ly emission with a shell model and find parameters values consistent with the observed ones. The absolute LyC escape fractions we find for GRB 191004B, GRB 050908 and GRB 060607A are of 0:35+0:10.0:11, 0:08+0:05.0:04 and :20+0:05.0:05, respectively. We compare the LyC escape fraction of LGRBs to the values of other LyC emitters found from the literature, showing that LGRB afterglows can be powerful tools to study LyC escape for faint high-redshift star-forming galaxies. Indeed we could push LyC leakage studies to much higher absolute magnitudes. The host galaxies of the three LGRB presented here have all M1600 >.19:5 mag, with the GRB 060607A host at M1600 >.16 mag. LGRB hosts may therefore be particularly suitable for exploring the ionizing escape fraction in galaxies that are too faint or distant for conventional techniques. Furthermore the time investment is very small compared to galaxy studies. (shrink)

The majority of Dutch physicians feel pressure when dealing with a request for euthanasia or physician-assisted suicide. This study aimed to explore the content of this pressure as experienced by general practitioners. We conducted semistructured in-depth interviews with 15 Dutch GPs, focusing on actual cases. The interviews were transcribed and analysed with use of the framework method. Six categories of pressure GPs experienced in dealing with EAS requests were revealed: emotional blackmail, control and direction by others, doubts about fulfilling the (...) criteria, counterpressure by patient’s relatives, time pressure around referred patients and organisational pressure. We conclude that the pressure can be attributable to the patient–physician relationship and/or the relationship between the physician and the patient’s relative, the inherent complexity of the decision itself and the circumstances under which the decision has to be made. To prevent physicians to cross their personal boundaries in dealing with EAS request all these different sources of pressure will have to be taken into account. (shrink)

Im Gegensatz zu L. v.Bertalanffy, der eine einheitliche biol. Theorie für nicht möglich hält, vertrete ich die These: Eine umfassende biologische Theorie, ausgehend von den Grundlagen der Physik, ist bis dato nicht ausschließbar.Betrachtet man die Frage ‘In welchem Sinne ist eine umfassende physikalische Theorie heute möglich?’, so ergibt sich, daß die Konzipierung je umfassenderer Theorien mit einer Beschränkung des vorhandenen empirischen Satzbestandes einerseits, mit einer Hinzunahme von Regeln für neue empirische Befunde andererseits verbunden ist. Wie am Beispiel einer Schar verschiedenartiger (...) statistischer Mechaniken gezeigt wird, oder wie der an einem experimentell nicht überprüfbaren Wert postulierte Übergang derGalilei- in dieLorentz-Transformation deutlich macht, stellen aufeinanderfolgende, abgeschlossene physikalische Theorien keineswegs Grenzfälle der vorausgehenden Theorien dar.Das unzureichende quantentheoretische Aufbauprinzip der Produkträume zur Konstituierung biol. Systeme weist ebenso wie die Nichtnachprüfbarkeit der Quantentheorie für makrophysikalische Körper auf einen umfassenderen Ansatz hin. Ohne das Hypothetische der einheitlichen Feldtheorie der Elementarteilchen imHeisenbergschen Entwurf zu berühren, erlaubt die nicht lineare Spinortheorie neben der Klassifizierung auch eine Voraussagemöglichkeit, obschon durch diese universelle Grundgleichung die Gesetze in den übrigen Teilen der Physik nicht vollständig bestimmt sind. Gleichwohl bietet dieser Ansatz keinen Schlüssel zur Lösung von Problemen im Grenzbereich zwischen Physik und Biologie.Mehr als das weite Feld biol. Theorien scheinen peinliche Vorurteile biol. Phänomenen gegenüber einer einheitlichen Theorie entgegenzustehen, Vorurteile, ob es sich um die willkürliche Abgrenzung zwischen Mikro- und Makrophänomenen handelt, ob die ungerechtfertigte Gegenüberstellung von qualitativen u. quantitativen Phänomenen im Vordergrund steht, ob ein über das kausale Argumentationsschema hinausgehendes Erklärungsschema gefordert wird, oder ob schließlich die anthropozentrischen Begriffsbildungen sowie die emotional bedingten Wesensfragen Platz greifen.Dessen ungeachtet stellen die Lebenserscheinungen ebenso wie die Verhaltenskombinate Mechanismen dar und sind durch Gesetze beschreibbar. Daher kann eine universelle Grundgleichung unter Hinzunahme weiterer, d.h. über den Bereich des Physikalischen hinausgehenden, empirischer Regeln nicht ausgeschlossen werden. In diesem Sinne ist eine umfassende biol. Theorie, ausgehend von den Grundlagen der Physik, möglich, ohne daß diese These eine Reduktion der Biologie auf die Physik zur Folge hätte. (shrink)

Evolutionary developmental biology (evo-devo) has undergone dramatic transformations since its emergence as a distinct discipline. This paper aims to highlight the scope, power, and future promise of evo-devo to transform and unify diverse aspects of biology. We articulate key questions at the core of eleven biological disciplines—from Evolution, Development, Paleontology, and Neurobiology to Cellular and Molecular Biology, Quantitative Genetics, Human Diseases, Ecology, Agriculture and Science Education, and lastly, Evolutionary Developmental Biology itself—and discuss why evo-devo is uniquely situated to substantially improve (...) our ability to find meaningful answers to these fundamental questions. We posit that the tools, concepts, and ways of thinking developed by evo-devo have profound potential to advance, integrate, and unify biological sciences as well as inform policy decisions and illuminate science education. We look to the next generation of evolutionary developmental biologists to help shape this process as we confront the scientific challenges of the 21st century. (shrink)

The thirteen essays of this collection converge on the theme of authority in an effort to analyze its general theoretical characteristics, to evaluate its historical development, and to propose solutions to contemporary social, political, and legal problems. Hannah Arendt's contribution, "What was Authority?" best expresses the awareness, reflected in several of the other essays, of a crisis in the understanding and acceptance of authority as a significant concept in political theory; and Carl J. Friedrich and Bertrand de Jouvenel provide perceptive (...) constructive attempts to grasp the nature of authority.--J. F. D. (shrink)

In 1795 the Marquis de Sade published his La Philosophic dans le boudoir, in which he proposed the use of induced abortion for social reasons and as a means of population control. It is from this time that medical and social acceptance of abortion can be dated, although previously the subject had not been discussed in public in modern times. It is suggested that it was largely due to de Sade's writing that induced abortion received the impetus which (...) resulted in its subsequent spread in western society. (shrink)

A partir de una encuesta por correo electrónico a estudiantes de Ingeniería en el SAI de la UAMA en un contexto de enseñanza remota forzado por la pandemia, se caracteriza la gestión de la docencia, desde la visión de los estudiantes, se realiza un diagnóstico de los aspectos relacionados. Es un estudio transversal con un análisis cualitativo y descriptivo de las respuestas. La gestión docente se ve afectada por factores inherentes al proceso, así como también por factores externos. Los resultados (...) obtenidos muestran que fue impactada fuertemente al realizarse el proceso totalmente vía remota especialmente, la comunicación e interacción alumno-profesor. (shrink)

Background: Issues concerning legislation and regulation with respect to the role of nurses in euthanasia and physician-assisted suicide gave the Minister for Health reason to commission a study of the role of nurses in medical end-of-life decisions in hospitals, home care and nursing homes.Aim: This paper reports the findings of a study of the role of nurses in euthanasia and physician-assisted suicide, conducted as part of a study of the role of nurses in medical end-of-life decisions. The findings for hospitals, (...) home care and nursing homes are described and compared.Method: A questionnaire was sent to 1509 nurses, employed in 73 hospitals, 55 home care organisations and 63 nursing homes. 1179 responses were suitable for analysis. The questionnaire was pilot-tested among 106 nurses, with a response rate of 85%.Results: In 37.0% of cases, the nurse was the first person with whom patients discussed their request for euthanasia or physician-assisted suicide. Consultation between physicians and nurses during the decision-making process took place quite often in hospitals and nursing homes and less frequently in home care situations . In some cases , nurses administered the euthanatics.Conclusions: The results show substantial differences between the intramural sector and the extramural sector , which are probably linked to the organisational structure of the institutions. Consultation between physicians and nurses during the decision-making process needs improvement, particularly in home care. Some nurses had administered euthanatics, although this task is by law exclusively reserved to physicians. (shrink)

The variety of residuated lattices includes a vast proportion of the classes of algebras that are relevant for algebraic logic, e.g., \-groups, Heyting algebras, MV-algebras, or De Morgan monoids. Among the outliers, one counts orthomodular lattices and other varieties of quantum algebras. We suggest a common framework—pointed left-residuated \-groupoids—where residuated structures and quantum structures can all be accommodated. We investigate the lattice of subvarieties of pointed left-residuated \-groupoids, their ideals, and develop a theory of left nuclei. Finally, we extend some (...) parts of the theory of join-completions of residuated \-groupoids to the left-residuated case, giving a new proof of MacLaren’s theorem for orthomodular lattices. (shrink)

Background: Discussing treatment risks has become increasingly important in medical communication. Still, despite regulations, physicians must decide how much and what kind of information to present. Objective: To investigate patients’ preference for information about a small risk of a complication of colonoscopy, and whether medical and personal factors contribute to such preference. To propose a disclosure policy related to our results. Design: Vignettes study. Setting: Department of Gastroenterology, Academic Medical Centre, the Netherlands. Patients: 810 consecutive colonoscopy patients. Intervention: A home-sent (...) questionnaire containing three vignettes. Vignettes varied in the indication for colonoscopy, complication severity and level of risk. Patients were invited to indicate their wish to be informed and the importance of such information. In addition, sociodemograhic, illness-related and psychological characteristics were assessed. Main outcome measurements: Wish to be informed and importance of information. Results: Of 810 questionnaires, 68% were returned. Patients generally wished to be informed about low-risk complications, regardless of the indication for colonoscopy or the severity of the complication. The level of risk did matter, though (OR = 2.48, SE = 0.28, p = 0.001). The information was considered less important if done for population screening purposes or diagnosis of colon cancer, if the complication was less severe (bleeding) and if the risk was smaller (0.01% and 0.1%). Patients’ information preference was also related to age, mood and coping style. Limitations: Difficulty of vignettes. Conclusions: Patients generally wish to be informed about all possible risks. However, this might become uninformative. A stepwise approach is suggested. (shrink)

Background: Although previous studies have shown an inverse relation between life meaning and eating disorder symptoms, the correlational nature of this evidence precludes causal inferences. Therefore, this study used an experimental approach to test the causal impact of life meaning on individuals' weight and shape concerns.Methods: Female students at risk for developing an eating disorder were randomly assigned to the control or the meaning condition, which involved thinking about and committing to pursue intrinsically valued life goals. A color-naming interference task (...) was used to assess the motivational salience of body-related stimuli, and self-report measures were used to assess participants' overvaluation of weight and shape.Results: The meaning manipulation was effective in activating intrinsically valued life goals. However, it did not result in lower self-reported overvaluation of weight and shape or lower color-naming interference effects of body-related stimuli, compared to the control condition. Post-hoc analyses suggested that baseline meaning in life was related to the impact of the manipulation.Conclusions: This experimental study did not provide evidence for a causal influence of life meaning on the overvaluation of weight and shape in a high-risk group. The current findings suggest that we first need to examine the relationship between life meaning and eating disorder symptoms in more detail, before implementing brief meaning manipulations in clinical practice. (shrink)

In this paper we present a paradigmatic example of the use in knowledge management of techniques from other fields, namely mathematical analysis. We also highlight that the Jacobi method presented here takes precedence over the better known Hungarian method. Finally, we signify that the Jacobi method represents the first known or recognized case of serendipity in both knowledge management and operational research. This paper thus demonstrates the intersection between knowledge management, mathematical analysis and operational research and how taking historical perspectives (...) are important for recognising future applications of knowledge management. This results in a better understanding of knowledge management and how it can be applied in the future. It has been shown how knowledge management relates to historical mathematical principles. (shrink)

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between (...) studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice. (shrink)

BackgroundPreprint usage is growing rapidly in the life sciences; however, questions remain on the relative quality of preprints when compared to published articles. An objective dimension of quality that is readily measurable is completeness of reporting, as transparency can improve the reader’s ability to independently interpret data and reproduce findings.MethodsIn this observational study, we initially compared independent samples of articles published in bioRxiv and in PubMed-indexed journals in 2016 using a quality of reporting questionnaire. After that, we performed paired comparisons (...) between preprints from bioRxiv to their own peer-reviewed versions in journals.ResultsPeer-reviewed articles had, on average, higher quality of reporting than preprints, although the difference was small, with absolute differences of 5.0% [95% CI 1.4, 8.6] and 4.7% [95% CI 2.4, 7.0] of reported items in the independent samples and paired sample comparison, respectively. There were larger differences favoring peer-reviewed articles in subjective ratings of how clearly titles and abstracts presented the main findings and how easy it was to locate relevant reporting information. Changes in reporting from preprints to peer-reviewed versions did not correlate with the impact factor of the publication venue or with the time lag from bioRxiv to journal publication.ConclusionsOur results suggest that, on average, publication in a peer-reviewed journal is associated with improvement in quality of reporting. They also show that quality of reporting in preprints in the life sciences is within a similar range as that of peer-reviewed articles, albeit slightly lower on average, supporting the idea that preprints should be considered valid scientific contributions. (shrink)