It has been assumed that at the whole organismal level, the mitochondrial reactive oxygen species (ROS) production is proportional to the oxygen consumption. Recently, a number of researchers have challenged this assumption, based on the observation that the ROS production per unit oxygen consumed in the resting state of mitochondrial respiration is much higher than that in the active state. Here, we develop a simple model to investigate the validity of the assumption and the challenge of it. The model highlights (...) the significance of the time budget that mitochondria operate in the different respiration states. The model suggests that under three physiologically possible conditions, the difference in ROS production per unit oxygen consumed between the respiration states does not upset the proportionality between the whole animal ROS production and oxygen consumption. The model also shows that mitochondrial uncoupling generally enhances the proportionality. (shrink)

BackgroundChronic airway diseases are prevalent and costly conditions. Interdisciplinary rehabilitation programs that include Acceptance and Commitment-based components could be important to tackle the vicious circle linking progression of the disease, inactivity, and psychopathological symptoms.MethodsA retrospective evaluation of routinely collected data of an interdisciplinary rehabilitation program was performed. The program included group sessions including patient education, breathing exercise, occupational therapy and an ACT-based psychological treatment, and individual sessions of physical therapy. Demographic data, clinical characteristics of the patients and the values of (...) outcome variables before treatment, at discharge, at 3 months, and at 6 months were extracted from medical records. Multiple imputation was employed to address missing data. Linear mixed models were employed to assess changes over time. Multivariable logistic regression was performed to assess predictors of a minimum clinically important change of health status from baseline to the 6-months follow-up.ResultsData from 31 patients with chronic obstructive pulmonary disease and 12 patients with bronchiectasis were extracted. Health status improved from baseline to discharge to the 3 months follow-up, but not to the 6 months follow-up. Anxiety and depression improved across all the time points. Quality of life did not improve over time. Having a worse health status at baseline and fewer depressive symptoms were significantly associated with achieving a minimum clinically important change of health status at 6 months. The effects of the interdisciplinary program were not different for patients with COPD or with bronchiectasis.DiscussionInterdisciplinary programs including ACT-based components are promising treatments for the rehabilitation of patients with chronic airway diseases. (shrink)

HIV remission clinical researchers are increasingly seeking study participants who are diagnosed and treated during acute HIV infection—the brief period between infection and the point when the body creates detectable HIV antibodies. This earliest stage of infection is often marked by flu-like illness and may be an especially tumultuous period of confusion, guilt, anger, and uncertainty. Such experiences may present added ethical challenges for HIV research recruitment, participation, and retention. The purpose of this paper is to identify potential ethical challenges (...) associated with involving acutely diagnosed people living with HIV in remission research and considerations for how to mitigate them. We identify three domains of potential ethical concern for clinicians, researchers, and ethics committee members to consider: 1) Recruitment and informed consent; (2) Transmission risks and partner protection; and (3) Ancillary and continuing care. We discuss each of these domains with the aim of inspiring further work to advance the ethical conduct of HIV remission research. For example, experiences of confusion and uncertainty regarding illness and diagnosis during acute HIV infection may complicate informed consent procedures in studies that seek to recruit directly after diagnosis. To address this, it may be appropriate to use staged re-consent procedures or comprehension assessment. Responsible conduct of research requires a broad understanding of acute HIV infection that encompasses its biomedical, psychological, social, and behavioral dimensions. We argue that the lived experience of acute HIV infection may introduce ethical concerns that researchers and reviewers should address during study design and ethical approval. (shrink)

BackgroundHIV cure research involving cell and gene therapy has intensified in recent years. There is a growing need to identify ethical standards and safeguards to ensure cell and gene therapy (CGT) HIV cure research remains valued and acceptable to as many stakeholders as possible as it advances on a global scale.MethodsTo elicit preliminary ethical and practical considerations to guide CGT HIV cure research, we implemented a qualitative, in-depth interview study with three key stakeholder groups in the United States: (1) biomedical (...) HIV cure researchers, (2) bioethicists, and (3) community stakeholders. Interviews permitted evaluation of informants’ perspectives on how CGT HIV cure research should ethically occur, and were transcribed verbatim. We applied conventional content analysis focused on inductive reasoning to analyze the rich qualitative data and derive key ethical and practical considerations related to CGT towards an HIV cure.ResultsWe interviewed 13 biomedical researchers, 5 community members, and 1 bioethicist. Informants generated considerations related to: perceived benefits of CGT towards an HIV cure, perceived risks, considerations necessary to ensure an acceptable benefit/risk balance, CGT strategies considered unacceptable, additional ethical considerations, and considerations for first-in-human CGT HIV cure trials. Informants also proposed important safeguards to developing CGT approaches towards an HIV cure, such as the importance of mitigating off-target effects, mitigating risks associated with long-term duration of CGT interventions, and mitigating risks of immune overreactions.ConclusionOur study identified preliminary considerations for CGT-based HIV cure across three key stakeholder groups. Respondents identified an ideal cure strategy as one which would durably control HIV infection, protect the individual from re-acquisition, and eliminate transmission to others. Known and unknown risks should be anticipated and perceived as learning opportunities to preserve and honor the altruism of participants. Preclinical studies should support these considerations and be transparently reviewed by regulatory experts and peers prior to first-in-human studies. To protect the public trust in CGT HIV cure research, ethical and practical considerations should be periodically revisited and updated as the science continues to evolve. Additional ethics studies are required to expand stakeholder participation to include traditionally marginalized groups and clinical care providers. (shrink)

The Last Gift is an observational HIV cure-related research study conducted with people with HIV at the end of life (EOL) at the University of California San Diego. Participants agree to voluntarily donate blood and other biospecimens while living and their bodies for a rapid research autopsy postmortem to better understand HIV reservoir dynamics throughout the entire body. The Last Gift study was initiated in 2017. Since then, 30 volunteers were enrolled who are either (1) terminally ill with a concomitant (...) condition and have a prognosis of 6 months or less or (2) chronically ill with multiple comorbidities and nearing the EOL.Multiple ethical and logistical challenges have been revealed during this time; here, we share our lessons learnt and ethical analysis. Issues relevant to healthcare research include surrogate informed consent, personal and professional boundaries, challenges posed conducting research in a pandemic, and clinician burnout and emotional support. Issues more specific to EOL and postmortem research include dual roles of clinical care and research teams, communication between research personnel and clinical teams, legally required versus rapid research autopsy, identification of next of kin/loved ones and issues of inclusion. Issues specific to the Last Gift include logistics of body donation and rapid research autopsy, and disposition of the body as a study benefit.We recommend EOL research teams to have clear provisions around surrogate informed consent, rotate personnel to maintain boundaries, limit direct contact with staff associated with clinical care and have a clear plan for legally required versus research autopsies, among other recommendations. (shrink)

Our theoretical essay is an attempt to stimulate approximations and interactions between process philosophy - principally as proposed by Alfred North Whitehead (1861–1947) - and historical organizational studies. In order to reach this goal, we outline some theoretical and methodological possibilities of intersections among these two perspectives. Following the presentation of central concepts borrowed from a strong view of process, we present organizational history as a continuous emerging process of becoming. Following, we discuss recent literature reviews and attempts to categorize (...) intersections among process and historical organization studies. Finally, we discuss theoretical and methodological implications of intersections between these fields of study under the principles of the strong view of process. We also discuss the thematic as an opportunity for overcoming the paradigmatic hegemony and research limitations in the fields of organizational and historical organizational studies. We conclude by encouraging empirical testing and management applications of the ideas introduced in this work. (shrink)

While there is an extensive literature on the tendency to mimic emotional expressions in adults, it is unclear how this skill emerges and develops over time. Specifically, it is unclear whether infants mimic discrete emotion-related facial actions, whether their facial displays are moderated by contextual cues and whether infants’ emotional mimicry is constrained by developmental changes in the ability to discriminate emotions. We therefore investigate these questions using Baby-FACS to code infants’ facial displays and eye-movement tracking to examine infants’ looking (...) times at facial expressions. Three-, 7-, and 12-month-old participants were exposed to dynamic facial expressions of a virtual model which either looked at the infant or had an averted gaze. Infants did not match emotion-specific facial actions shown by the model, but they produced valence-congruent facial responses to the distinct expressions. Furthermore, only the 7- and 12-month-olds displayed negative responses to the model’s negative expressions and they looked more at areas of the face recruiting facial actions involved in specific expressions. Our results suggest that valence-congruent expressions emerge in infancy during a period where the decoding of facial expressions becomes increasingly sensitive to the social signal value of emotions. (shrink)

Objetivou-se estratificar fatores de risco para doenças cardiovasculares (DCV) em dez anos em jogadores de basquetebol em cadeiras de rodas. O percentual de risco cardiovascular foi estratificado pelos escores de Framingham (ERF) e de Risco Global (ERG). Dos treze jogadores avaliados, 38,46% apresentava sobrepeso e obesidade e 77%, alterações na porcentagem de gordura corporal e na circunferência abdominal. O ERF identificou 15,38% dos jogadores com risco intermediário para desenvolvimento de DCV e pelo ERG, 15,4% dos homens apresentava risco intermediário, 7,7% (...) alto risco por diabetes e 7,7% muito alto risco por doenças ateroscleróticas. Os resultados de composição corporal demonstram uma predisposição para desenvolvimento de DCV, sendo que o ERG identificou indivíduos com alto risco e muito alto risco. Conclui-se que a identificação dos fatores de risco é útil para que ocorra uma maior prevenção das DCV e aconselhamento adequado sobre adoção de hábitos de vida saudáveis por esses indivíduos. (shrink)

Este artigo é um relato de experiência do processo de implantação do ambiente virtual de aprendizagem do Programa Primeira Infância Melhor (PIM). O PIM é uma política pública intersetorial de promoção do desenvolvimento integral na primeira infância, implantada no Estado do Rio Grande do Sul, Brasil. Entre as atribuições do Governo do Estado está a formação das equipes em mais de 200 municípios. Por causa das restrições impostas pela pandemia de coronavirus, a política deixou de realizar formações presenciais e, de (...) forma emergencial, promoveu formações remotas, utilizando a ferramenta Google Drive. A partir desta experiência, foi decidido implantar uma plataforma de formação online. Para tanto, foi realizado um longo processo de planejamento, com análise dos materiais existentes, adequação aos objetivos pretendidos, criação do ambiente virtual e realização de uma formação piloto na modalidade educação à distância. (shrink)

Figurines de terre cuite (H. Aurigny, Fr. Croissant) Tous les fragments sont désormais enregistrés dans la base FileMakerPro, terminée pour l’essentiel en 2013 et complétée en 2015. La mission prévue en 2014 ayant été annulée par l’École française d’Athènes pour raisons budgétaires, un réexamen à distance de l’ensemble du matériel avait néanmoins permis d’en esquisser à distance le classement typologique et d’élaborer quelques hypothèses, qui ont pu être vérifiées et affinées sur place en mai...

Plasmodium falciparum is the most deadly human malarial parasite, responsible for an estimated 207 million cases of disease and 627,000 deaths in 2012. Recent studies reveal that the parasite actively regulates a large fraction of its genes throughout its replicative cycle inside human red blood cells and that epigenetics plays an important role in this precise gene regulation. Here, we discuss recent advances in our understanding of three aspects of epigenetic regulation in P. falciparum: changes in histone modifications, nucleosome occupancy (...) and the three‐dimensional genome structure. We compare these three aspects of the P. falciparum epigenome to those of other eukaryotes, and show that large‐scale compartmentalization is particularly important in determining histone decomposition and gene regulation in P. falciparum. We conclude by presenting a gene regulation model for P. falciparum that combines the described epigenetic factors, and by discussing the implications of this model for the future of malaria research. (shrink)

Purpose: This study aimed to develop a stroke effectiveness test in table tennis based on the temporal game structure to assess the ball speed and ball placement of the players, with a purpose to analyze its reproducibility and validity. Methods: Nineteen male table tennis players participated in this study. The test was performed twice during the first session and once during the second session to assess the intrasession and intersession reproducibility, respectively. Moreover, the test was examined on its ability to (...) discriminate between regional and local performance-level players and on the relationship between the test results and the table tennis performance to assess the discriminant and concurrent validity, respectively. In general, the test consisted of 11 simulated rallies of 2–5 balls with the effort and rest ratio of 0.5, and focused on attack with offensive strokes at defensive balls delivered by a robot randomly between the left and right positions on the table. Results: Ball speed, ball placement, and ball speed-ball placement index showed satisfactory reliability and agreement outcomes. Additionally, the Bland-Altman plots show the systematic error of the analyses closer to 0, and that most values were within the limits of agreements. Concerning validity analyses, regional players had higher scores of ball placement and ball speed-ball placement index as well as made fewer errors than local players. Moreover, ball placement, ball speed-ball placement index, and percentage error presented a strong and significant correlation with table tennis performance. However, ball speed was slightly different between the regional than local players and this variable was not related to table tennis performance. Conclusion: Our findings show evidences that the test is reproducible. Moreover, discriminant and concurrent validity are confirmed for ball placement and ball speed-ball placement index. (shrink)

Gperhard Heinzmann, Rédacteur en chef La philosophie est la mère des sciences. Il faut avoir une bonne mémoire pour se le rappeler. Quel bonheur lorsque ce rappel vient d’une collègue qui ne l’a pas appris, mais qui éprouve la nécessité de questionner sa pratique scientifique et actualise ainsi l’ancienne métaphore! C’était le cas de Catherine Dufour. On se connaissait vaguement depuis l’école maternelle des Trois Maisons que fréquentaient nos enfants. Je fus donc très heureux de découvrir,...

A review on the educational experience of students with disabilities, based on qualitative and quantitative surveys, questions the stated objectives of inclusive education policies. These studies show a more favourable experience in the specialized classe, due to a deteriorated relationship to schooling in the regular classroom and a sense of isolation and incompetence developed faced of difficulties. Research conducted in a bilingual French sign language-French written device, in secondary school with deaf and hearing students schooled together in the regular classroom, (...) suggests other stories. The way in which school and teaching situations are conducted within this aid system, engages these students in a rewarding and capaciting experience, to be a recognized student in the classroom and among peers. Learning French sign language, the work of translators at the linguistic as well as pedagogical and educational level, the supporting role of auxiliary teaching systems, participate in the process of accessing school situations, especially to educational accessibility, thus providing students with a space of opportunity to attend school. (shrink)

BackgroundThe pursuit of a cure for HIV is a high priority for researchers, funding agencies, governments and people living with HIV (PLWH). To date, over 250 biomedical studies worldwide are or have been related to discovering a safe, effective, and scalable HIV cure, most of which are early translational research and experimental medicine. As HIV cure research increases, it is critical to identify and address the ethical challenges posed by this research.MethodsWe conducted a scoping review of the growing HIV cure (...) research ethics literature, focusing on articles published in English peer-reviewed journals from 2013 to 2021. We extracted and summarized key developments in the ethics of HIV cure research. Twelve community advocates actively engaged in HIV cure research provided input on this summary and suggested areas warranting further ethical inquiry and foresight via email exchange and video conferencing.DiscussionDespite substantial scholarship related to the ethics of HIV cure research, additional attention should focus on emerging issues in six categories of ethical issues: (1) social value (ongoing and emerging biomedical research and scalability considerations); (2) scientific validity (study design issues, such as the use of analytical treatment interruptions and placebos); (3) fair selection of participants (equity and justice considerations); (4) favorable benefit/risk balance (early phase research, benefit-risk balance, risk perception, psychological risks, and pediatric research); (5) informed consent (attention to language, decision-making, informed consent processes and scientific uncertainty); and (6) respect for enrolled participants and community (perspectives of people living with HIV and affected communities and representation).ConclusionHIV cure research ethics has an unfinished agenda. Scientific research and bioethics should work in tandem to advance ethical HIV cure research. Because the science of HIV cure research will continue to rapidly advance, ethical considerations of the major themes we identified will need to be revisited and refined over time. (shrink)

“Financial Conflicts and Clinical Research’”: a letter from Karin Meyers about “Community Hospital Oversight of Clinical Investigators’ Financial Relationships ”.

How does science create knowledge? Epistemic cultures, shaped by affinity, necessity, and historical coincidence, determine how we know what we know. In this book, Karin Knorr Cetina compares two of the most important and intriguing epistemic cultures of our day, those in high energy physics and molecular biology. The first ethnographic study to systematically compare two different scientific laboratory cultures, this book sharpens our focus on epistemic cultures as the basis of the knowledge society.

Laborie and Hessayon bring rare prophetic and millenarian texts to an international audience by presenting sources from all over Europe (broadly defined), and across the early modern period in English for the first time.

Philosophy with children (P4C) 1 presents significant positive challenges for educators. Its 'community of enquiry' pedagogy assumes not only an epistemological shift in the role of the educator, but also a different ontology of 'child' and balance of power between educator and learner. After a brief historical sketch and an outline of the diversity among P4C practitioners, epistemological uncertainty in teaching P4C is crystallised in a succinct overview of theoretical and practical tensions that are a direct result of the implementation (...) of P4C in mainstream education. These recurring pedagogical tensions in my practice as P4C teacher, teacher educator and mentor of teacher educators cause disequilibrium that opens up rich opportunities for philosophy of education in supporting novice P4Cers. Disequilibrium is a positive force that opens up a space in which educators need to reflect upon their values, their beliefs about learning and teaching, and ultimately encourages educators to rethink their own role. Plato's metaphor of the stingray highlights the role of the P4C teacher educator as model of the P4C teacher in any setting: 'to numb and to be numbed'. The P4C community and its institutions need to address the questions arising from these pedagogical tensions; and this needs to be done with integrity, that is, in communities of enquiry that include children. If not, in the long term, a more instrumental version of P4C may prevail. (shrink)

Die Rassentheorie, die Geschichtsphilosophie, die Ästhetik und die Naturteleologie haben eine Gemeinsamkeit: In all diesen Themengebieten entwickelte Immanuel Kant ein Denken der Zweckmässigkeit. Die Fokussierung auf diesen Strang macht eine Verbindung sichtbar, die von seinen frühen Schriften zu den unterschiedlichen »Rassen« der Menschen hin zur Kritik der Urteilskraft und damit zu seiner Selbstreflexion über die kritische Philosophie reicht. Karin Hostettler arbeitet das mit diesem Denken verbundene Othering und die damit einhergehende Selbstaffirmation heraus und zeigt so die Selbstverortung der kritischen Philosophie (...) in einer kolonialen Episteme auf. (shrink)

Some philosophers claim that young children cannot do philosophy. This paper examines some of those claims, and puts forward arguments against them. Our beliefs that children cannot do philosophy are based on philosophical assumptions about children, their thinking and about philosophy. Many of those assumptions remain unquestioned by critics of Philosophy with Children. My conclusion is that the idea that very young children can do philosophy has not only significant consequences for how we should educate young children, but also for (...) how adults should do philosophy; and that further research is urgently needed. (shrink)

This paper suggests that the practice of anamnesis—the taking of a patient history in preparation for making a diagnosis, as well as the related form of investigation, historia—offers a way to understand the role of medical collections in generating medical knowledge. Anamnesis derives from ancient Greek “recollecting” or “opening of memory,” and “taking a history” from historia, an ancient and early modern epistemic practice of gathering empirical observations from the past and present. Doctors and medical researchers perform, this paper argues, (...) a form of anamnesis when they access collections—of pathological organs, experimental animals, diagnostic slides, samples, and data—and the collections may in turn be seen as constituting institutional and disciplinary memories. It moreover shows that doctors and medical researchers in their work with collections negotiate two ways of organizing observations that are also present in an anamnesis. One way clusters and classifies observations, while the other traces developments and requires significant past observations to understand the present. This double nature plays out in different ways in different historical collections. Last, the paper itself may also be seen as performing an anamnesis: looking for patterns and tracing a development in medical history. It “opens the memory” of medical collection practices, and shows that medicine is past-heavy and that the past plays a central role in modern biomedicine. Anamnesis is thus used as a historiographical stance that seeks to understand present practices of generating knowledge about diseases through an inquiry into the past. (shrink)

In her book Epistemic Injustice: Power and the Ethics of Knowing , Miranda Fricker introduces the helpful notion of “identity prejudice” as “a label for prejudices against people qua social type” . She focuses on race, class and gender, and Michael Hand in his article What Do Kids Know? A response to Karin Murris is indeed correct when he states that I have applied her arguments to age as a category of epistemic exclusion.I argue that among the usual contenders of (...) epistemic prejudices, we also need to be cognisant of adults’ implicit and explicit assumptions and prejudices about child and childhood. However, Hand incorrectly uses Fricker’s ideas to reject my proposal to include child as being on the receiving end of epistemic injustice. A close reading of some passages about stereotyping will show why this is the case and why his own claim that “children typically are immature, ill-informed and endearing” will turn out to .. (shrink)

Humboldts texttheoretischer Ansatz, dessen Einfluß auf die moderne (Text-)Linguistik größer ist als bisher wahrgenommen, wird im ersten Teil dieses Bandes erstmals zusammenhängend nachgewiesen.

Karin Michels Werk hebt sich von der bisherigen Literatur zum Thema deutlich ab, indem sie zeigt, dass Kants Zeittheorie nicht ohne seine Theorie des Raumes und seine Idealismuskritik verständlich zu machen ist. Die Autorin legt eine Rekonstruktion von Kants Beweis der genuinen Subjektivität der Zeit vor. Sie berücksichtigt dabei Beweisform sowie Beweisinhalt und setzt sich außerdem durchgehend mit Kant-Kommentatoren und -kritikern auseinander. Verständlich wird dadurch nicht nur Kants radikaler Neuansatz in der Zeitphilosophie, sondern auch die Bedeutung des Beweises für sein (...) Gesamtprojekt der Vernunftkritik. (shrink)