We review here the data indicating a role for epidermal growth factor receptor (EGF receptor) signalling in early mouse development. Embryonic development of the metazoan embryo generally begins with the formation of a cystic structure and epithelial layers that subsequently form anlagen of the definitive body parts and organs. For the mammalian embryo, this cystic structure is a blastocyst whose wall consists of trophectoderm, the first epithelium to develop during mammalian embryogenesis. The onset of expression and function of EGF receptors (...) is coincident with the onset of trophectoderm development. Modulating EGF receptor expression and function modulates trophectoderm differentiation, leading to the hypothesis that functional EGF receptors participate in the induction of trophectoderm development and perhaps of other embryonic epithelial derivatives such as nervous tissues. (shrink)

Knowledge of eukaryotic life cycles and associated genome dynamics stems largely from research on animals, plants, and a small number of “model” (i.e., easily cultivable) lineages. This skewed sampling results in an underappreciation of the variability among the many microeukaryotic lineages, which represent the bulk of eukaryotic biodiversity. The range of complex nuclear transformations that exists within lineages of microbial eukaryotes challenges the textbook understanding of genome and nuclear cycles. Here, we look in‐depth at Foraminifera, an ancient (∼600 million‐year‐old) lineage (...) widely studied as proxies in paleoceanography and environmental biomonitoring. We demonstrate that Foraminifera challenge the “rules” of life cycles developed largely from studies of plants and animals. To this end, we synthesize data on foraminiferal life cycles, focusing on extensive endoreplication within individuals (i.e., single cells), the unusual nuclear process calledZerfall, and the separation of germline and somatic function into distinct nuclei (i.e., heterokaryosis). These processes highlight complexities within lineages and expand our understanding of the dynamics of eukaryotic genomes. (shrink)

Background Pragmatic randomized controlled trials are designed to evaluate the effectiveness of interventions in real-world clinical conditions. However, these studies raise ethical issues for researchers and regulators. Our objective is to identify a list of key ethical issues in pragmatic RCTs and highlight gaps in the ethics literature. Methods We conducted a scoping review of articles addressing ethical aspects of pragmatic RCTs. After applying the search strategy and eligibility criteria, 36 articles were included and reviewed using content analysis. Results Our (...) review identified four major themes: 1) the research-practice distinction; 2) the need for consent; 3) elements that must be disclosed in the consent process; and 4) appropriate oversight by research ethics committees. 1) Most authors reject the need for a research-practice distinction in pragmatic RCTs. They argue that the distinction rests on the presumptions that research participation offers patients less benefit and greater risk than clinical practice, but neither is true in the case of pragmatic RCTs. 2) Most authors further conclude that pragmatic RCTs may proceed without informed consent or with simplified consent procedures when risks are low and consent is infeasible. 3) Authors who endorse the need for consent assert that information need only be disclosed when research participation poses incremental risks compared to clinical practice. Authors disagree as to whether randomization must be disclosed. 4) Finally, all authors view regulatory oversight as burdensome and a practical impediment to the conduct of pragmatic RCTs, and argue that oversight procedures ought to be streamlined when risks to participants are low. Conclusion The current ethical discussion is framed by the assumption that the function of research oversight is to protect participants from risk. As pragmatic RCTs commonly involve usual care interventions, the risks may be minimal. This leads many to reject the research-practice distinction and question the need for informed consent. But the function of oversight should be understood broadly as protecting the liberty and welfare interest of participants and promoting public trust in research. This understanding, we suggest, will focus discussion on questions about appropriate ethical review for pragmatic RCTs. (shrink)

Philosophy of religion comprises philosophical reflection on a wide range of religious and religiously significant phenomena: religious belief, doctrine and practice in general; the phenomenology and cognitive significance of religious experience; the authority and reliability of religious testimony; the significance of religious diversity and disagreement; the relationship between religion (or God, or the gods) and morality; the doctrines, practices and modes of cognition distinctive to particular religious traditions; and so on. It is as old as philosophy itself and has been (...) a standard part of Western philosophy in every period (see Religion, history of philosophy of). Since the latter half of the twentieth century, there has been a great growth of interest in it, and the range of topics that philosophers of religion have considered has expanded considerably. (shrink)

The earlier volume in this series dealt with two religions of Indian origin, namely, Buddhism and Jainism. The Indian religious scene, however, is characterized by not only religions which originated in India but also by religions which entered India from outside India and made their home here. Thus religious life in India has been enlivened throughout its history by the presence of religions of foreign origin on its soil almost from the very time they came into existence. This volume covers (...) three such religions—Zoraoastrianism, Judaism, and Islam. In the case of Zoraostianism, even its very beginnings are intertwined with India, as Zoroastrianism reformed a preexisting religion which had strong links to the Vedic heritage of India. This relationship took on a new dimension when a Zoroastrian community, fearing persecution in Persia after its Arab conquest, sought shelter in western India and ultimately went on to produce India’s pioneering nationalist in the figure of Dadabhai Naoroji ( 1825-1917), also known as the Grand Old Man of India. Jews found refuge in south India after the destruction of the Temple by the Romans in 70 C.E. and have remained a part of the Indian religious scene since then, some even returning to Israel after it was founded in 1948. Islam arrived in Kerala as soon as it was founded and one of the earliest mosques in the history of Islam is found in India. Islam differs from the previously mentioned religions inasmuch as it went on to gain political hegemony over parts of the country for considerable periods of time, which meant that its impact on the religious life of the subcontinent has been greater compared to the other religions. It has also meant that Islam has existed in a religiously plural environment in India for a longer period than elsewhere in the world so that not only has Islam left a mark on India, India has also left its mark on it. Indeed all the three religions covered in this volume share this dual feature, that they have profoundly influenced Indian religious life and have also in turn been profoundly influenced by their presence in India. (shrink)

This paper develops an information-sensitive theory of the semantics and probability of conditionals and statements involving epistemic modals. The theory validates a number of principles linking probability and modality, including the principle that the probability of a conditional If A, then C equals the probability of C, updated with A. The theory avoids so-called triviality results, which are standardly taken to show that principles of this sort cannot be validated. To achieve this, we deny that rational agents update their credences (...) via conditionalization. We offer a new rule of update, Hyperconditionalization, which agrees with Conditionalization whenever nonmodal statements are at stake but differs for modal and conditional sentences. (shrink)

Dans ce volume collectif, J. Albisetti, J. Goodman et Rebecca Rogers nous emmènent dans un tour européen du développement de l’enseignement secondaire pour les filles. Les contributeurs proposent deux pistes principales : une vue d’ensemble des histoires nationales de l’enseignement des filles ; et une présentation des pistes de recherche à suivre. Bien que Girls’ Secondary Education in the Western World soit organisé par pays, les directeurs et les auteurs soulignent les multiples connexions...

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)

Cell communication is crucial for many aspects of growth and differentiation during the development of the nematode Caenorhabditis elegans. Two genes, glp‐1 and lin‐12, mediate a number of known cell–cell interactions. Genetic and molecular analyses of these two genes lead to the conclusion that they are structurally and functionally related. We summarize these studies as well as those involving the identification of other genes that interact with glp‐1 and / or lin‐12.

Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need (...) to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent. (shrink)

Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need (...) to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent. (shrink)

Ever so often in the UK, there is a flurry of activity around the information requirements of donor-conceived individuals. In April 2013, it was the launch of a report from the Nuffield Council on Bioethics that brought the issue back to public consciousness.1Since 1991, information about treatment with donor gametes or embryos has been collected by the Human Fertilisation and Embryology Authority . Since then, over 35 000 donor-conceived individuals have been born through treatment in licensed clinics. Medical information and (...) information about donors’ appearance are collected by clinics, and donors are encouraged to put together a ‘pen portrait’ giving information about themselves for any resulting children. One focus of the new report is on improving the quality and quantity of information available about donors.Traditionally, gamete and embryo donations were practised on an anonymous basis, so that those born as a result of such donation may receive only non-identifying information about the donor when they reach the age of 18 . This changed in 2005 when donor anonymity was removed so that anyone donating after that time could be identified to individuals born as a result of the treatment. Those who have donated in the past are also able to reregister as identifiable donors. Much concern was expressed at the time that this would exacerbate the shortage of donors although the Nuffield Council on Bioethics reports that, 8 years on, those clinics that actively recruit donors appear to be successful in finding sufficient donors. The report recommends that the option of anonymous donation should not be reintroduced.A big issue of debate in the UK has been, and continues to be, whether parents should tell their …. (shrink)

Until recently, leading work on the philosophy of thought experiments mistakenly credited Mach with coining the term. While Ørsted’s prior use has become more widely acknowledged, there remains a c...

BACKGROUND: Hallucinations and delusions that complicate Parkinson’s disease could lead to nursing home placement and are linked to increased mortality. Cognitive impairments are typically associated with the presence of hallucinations but there are no data regarding whether such a relationship exists with delusions. OBJECTIVE: We hypothesized that hallucinations would be associated with executive and visuospatial disturbance. An exploratory examination of cognitive correlates of delusions was also completed to address the question of whether they differ from hallucinations. METHODS: 144 PD subjects (...) completed a neuropsychological battery to assess cognition and the SAPS to examine psychosis. Correlational analyses assessed associations between hallucinations and delusions with cognitive domains. RESULTS: 48 subjects reported psychotic symptoms: 25 experienced hallucinations without delusions, 23 had symptoms dominated by delusions. Severity and/or number of hallucination subtypes were significantly correlated with lower scores in language, memory, attention, executive functioning, and visuospatial ability. Correlations with delusions were non-significant. Tests of differences in the size of the correlations between groups revealed a significant relationship between language and visuospatial performance with hallucinations. CONCLUSIONS: Cognitive correlates of hallucinations and delusions appear to be different in PD, suggesting distinct pathogenic mechanisms and possibly anatomical substrates. Hence, delusions may not share the same associations with dementia as hallucinations. Since this is a new finding, further studies will be needed to confirm our results. (shrink)

The increasing use of cluster randomised trials in low-resource settings raises unique ethical issues. TheOttawa Statement on the Ethical Design and Conduct of Cluster Randomised Trialsis the first international ethical guidance document specific to cluster trials, but it is unknown if it adequately addresses issues in low-resource settings. In this paper, we seek to identify any gaps in theOttawa Statementrelevant to cluster trials conducted in low-resource settings. Our method is (1) to analyse a prototypical cluster trial conducted in a low-resource (...) setting (PURE Malawi trial) with theOttawa Statement; (2) to identify ethical issues in the design or conduct of the trial not captured adequately and (3) to make recommendations for issues needing attention in forthcoming revisions to theOttawa Statement. Our analysis identified six ethical aspects of cluster randomised trials in low-resource settings that require further guidance. The forthcoming revision of theOttawa Statementshould provide additional guidance on these issues: (1) streamlining research ethics committee review for collaborating investigators who are affiliated with other institutions; (2) the classification of lay health workers who deliver study interventions as health providers or research participants; (3) the dilemma experienced by investigators when national standards seem to prohibit waivers of consent; (4) the timing of gatekeeper engagement, particularly when researchers face funding constraints; (5) providing ancillary care in health services or implementation trials when a routine care control arm is known to fall below national standards and (6) defining vulnerable participants needing protection in low-resource settings. (shrink)

Today, public health regulation at all levels faces unprecedented challenges both at home and abroad. The September 11, 2001 attacks on New York and Washington, D.C., by the Al Qaeda terrorist network and the anthrax bioterrorism that followed shortly thereafter have put public health regulation at the forefront of homeland security. The anthrax scare, in particular, has greatly tested the American public health system, calling into question whether the United States and its component states and localities are prepared to handle (...) a major outbreak of infectious disease, such as smallpox, in a future bioterrorist action. While the response of public health agencies was commendable, especially in light of the magnitude of the assaults, it is manifestly clear that the American public health system will be hard pressed to meet similar challenges that may lie ahead.The events of fall 2001 follow a period of major challenges for public health. The AIDS pandemic has killed millions of people throughout the globe, especially in Africa and other parts of the developing world. (shrink)

This article identifies a papyrus in Warsaw, P.Vars. 6, as a fragment of the large Latin–Greek glossary known as Ps.-Philoxenus. That glossary, published in volume II of G. Goetz's Corpus Glossariorum Latinorum on the basis of a ninth-century manuscript, is by far the most important of the bilingual glossaries surviving from antiquity, being derived from lost works of Roman scholarship and preserving valuable information about rare and archaic Latin words. It has long been considered a product of the sixth century (...) a.d., but the papyrus dates to c.200, and internal evidence indicates that the glossary itself must be substantially older than that copy. The Ps.-Philoxenus glossary is therefore not a creation of Late Antiquity but of the Early Empire or perhaps even the Republic. Large bilingual glossaries in alphabetical order must have existed far earlier than has hitherto been believed. (shrink)

Various notions of independence of observables have been proposed within the algebraic framework of quantum field theory. We discuss relationships between these and the recently introduced notion of logical independence in a general operator-algebraic context. We show that C*-independence implies an analogue of classical independence.

In a recent paper [1], O. F. de Alcantara Bonfim, J. Florencio, and F. C. S´ a Barreto claim to have found numerical evidence of chaos in the motion of a Bohmian quantum particle in a double square-well potential, for a wave function that is a superposition of five energy eigenstates. But according to the result proven here, chaos for this motion is impossible. We prove in fact that for a particle on the line in a superposition of n + (...) 1 energy eigenstates, the Bohm motion x(t) is always quasiperiodic, with (at most) n frequencies. This means that there is a function F (y1, . . . , yn) of period 2π in each of its variables and n frequencies ω1, . . . , ωn such that x(t) = F (ω1t, . . . , ωnt). The Bohm motion for a quantum particle of mass m with wave function ψ = ψ(x, t), a solution to Schrödinger’s equation, is defined by.. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Bibliography of Resources by and about André E. Hellegers*Compiled by Doris Mueller Goldstein (bio)This bibliography is derived from the holdings of the National Reference Center for Bioethics Literature and the BIOETHICSLINE© database (both of which are at the Kennedy Institute of Ethics and supported by the National Library of Medicine); the archives of Lauinger Library, Georgetown University; the Medline databases of the National Library of Medicine; the WorldCat (...) database of OCLC, Dublin, Ohio, and selected Internet sites.Primarily comprised of writings by Dr. Hellegers, the list also includes interviews and media programs in which he participated, as well as writings about him that were written following his death. The arrangement within each section is by date. The 231 authored pieces reflect the transition from Dr. Hellegers’s early career as a researcher in fetal physiology at Johns Hopkins Medical School, where he published his first research report at the age of 29, to the early years of the Kennedy Institute, where he produced so many provocative columns on bioethical issues that influenced the growth of the field.Due to the diversity of sources and the 40-year time span covered, there are some variations in bibliographic style. Time and availability constraints precluded verifying all of the citations with the original documents. Any additions or corrections should be submitted to the compiler.Works Authored by André E. HellegersNo Date Ethical Issues in Sterilization of the Retarded. Unpublished paper.1956Vitamin B12 Serum Level and Pregnancy. American Journal of Clinical Nutrition 4: 440+, 1956. [With Bacon F. Chow and Kunio Okuda] [End Page 89]1957Vitamin B12 Absorption in Pregnancy and in the Newborn. American Journal of Clinical Nutrition 5: 327+, 1957. [With Bacon F. Chow, Robert E. L. Nesbitt, Kunio Okuda, and David W. Smith]1958The Effects of Acute Hypoxia on the Osmotic Pressure of the Plasma. Quarterly Journal of Experimental Physiology 43: 197+, 1958. [With Donald H. Barron, Frederick C. Battaglia, and Giacomo Meschia]Studies on the Absorption of Vitamin B12 in Human Pregnancy with Especial Reference to the Effect of D-Sorbitol. American Journal of Obstetrics and Gynecology 76: 91+, 1958. [With Bacon F. Chow, Harry Prystowsky, and Vernon Wong]1959The Alveolar PCO2 and PO2 in Pregnant and Nonpregnant Women at Altitude. Proceedings of the Society for Clinical Investigation 38: 1010+, 1959. [With Donald Barron, William Huckabee, Giacomo Meschia, James Metcalfe, and Harry Prystowsky]A Comparison of the Oxygen Dissociation Curves of the Bloods of Maternal and Fetal Goats at Various pHs. Quarterly Journal of Experimental Physiology 44: 215–21, July 1959. [With Donald Barron, Giacomo Meschia, Harry Prystowsky, and A. Stark Wolkoff]Fetal Blood Studies. XII. On the Relationship Between the Position of the Oxygen Dissociation Curve of Human Fetal Blood and Adult Fetal Hemoglobin. American Journal of Obstetrics and Gynecology 77: 585+, 1959. [With Paul D. Bruns, Julian Cotter, and Harry Prystowsky]Fetal Blood Studies. XIV. A Comparative Study of the Oxygen Dissociation Curve of Nonpregnant, Pregnant and Fetal Human Blood. American Journal of Obstetrics and Gynecology 78: 489–93, September 1959. [With Paul D. Bruns and Harry Prystowsky]Fetal Blood Studies. XVI. On the Changes in Total Osmotic Pressure and Sodium and Potassium Concentration of Amniotic Fluid During the Course of Human Gestation. Surgery, Gynecology and Obstetrics 109: 509–12, October 1959. [With Frederick Battaglia, Paul D. Bruns, Harry Prystowsky, and Clayton Smisson]Further Observations on the Metabolism of Vitamin B12 in Human Pregnancy. American Journal of Obstetrics and Gynecology 77: 1+, 1959. [With Bacon F. Chow, Harry Prystowsky, Bruno Ranke, and Elma Ranke]The Oxygen Dissociation Curves of the Bloods of Adult and Fetal Llamas. Federation Proceedings 18, 1959. [With Donald Barron, William Huckabee, Giacomo Meschia, James Metcalfe, and Harry Prystowsky] [End Page 90]Transfer of Oxygen Across the Sheep Placenta at High Altitude. Federation Proceedings 18, 1959. [With Donald Barron, William Huckabee, Giacomo Meschia, and Harry Prystowsky]Uterine Blood Flow and Metabolism in Pregnant Sheep at High Altitude. Federation Proceedings 18, 1959. [With Donald Barron, William Huckabee, Giacomo Meschia, James Metcalfe, and Harry Prystowsky]Uterine Blood Flow and Metabolism in Unanesthetized Pregnant Sheep. Federation Proceedings 18, 1959. [With Donald Barron, William Huckabee, Giacomo... (shrink)

: The medieval Karaite grammarian and exegete Abū l-Faraj Hārūn b. al-Faraj was a broad reader of the literature available in Arabic, in a variety of genres. Earlier studies have demonstrated that in his grammatical works on the Hebrew language, Hārūn adapted discussions from well-known compositions focused on Arabic and the Qurʾān. The following examination of Hārūn’s treatment of the subject of biblical majāz, non-literal language, aims to show that in constructing his sophisticated and innovative discussion of the topic, the (...) Karaite scholar read widely – and adapted creatively – incorporating the methods of a variety of genres in Arabic, including uṣūl al-naḥw, uṣūl al-fiqh and even iʿjāz al-Qurʾān and combining them together with earlier Jewish and Karaite scholarly tradition to produce what seems to be the first comprehensive discussion of non-literal language in Judeo-Arabic. (shrink)

Biofeedback mechanisms (a) between individuals, (b) between the individual and the society structures which shape individual cognitions, and (c) within the individual genetic biochemical circulation, may explain the diversity of trustworthiness potential and the option of mutual trust for every individual in any given society.

Prepared for NATO conference on Kondratieff Waves and Warfare, Covilha, Portugal, Feb. 2005. Published in T. C. Devezas, ed., Kondratieff Waves, Warfare and World Security. Amsterdam : IOS, 2006. Also online here.: My work in the mid-1980s on Kondratieff waves tried to explain long waves in terms of causal relationships among six main variables : war, production, prices, innovation, investment, and real wages. I emphasized war as a central element ; saw production waves as (...) - Économie et Marxisme – (...) Nouvel article. (shrink)

A sketchy subquantum theory deeply influenced by Wheeler’s ideas (Am. J. Phys. 51:398–404, 1983) and by the de Broglie-Bohm interpretation (Goldstein in Stanford Encyclopedia of Philosophy, 2006) of quantum mechanics is further analyzed. In this theory a fundamental system is defined as a dual entity formed by bare matter and a methodological probabilistic classical Turing machine. The evolution of the system would be determined by three Darwinian informational regulating principles. Some progress in the derivation of the postulates of quantum (...) mechanics from these regulating principles is reported. The entanglement in a bipartite system is preliminarily considered. (shrink)