Although Next Generation Sequencing (NGS) has increased our ability to test and diagnose, its results are often not clear-cut and require a complex interpretation and negotiation process by both healthcare professionals and patients involved. In this paper, we explore how diagnoses identified through NGS are socially shaped under influence of the broader social context. Using an analytical framework stemming from the sociology of health and illness and science and technology studies, with a focus on the construction of diagnosis and the (...) role of uncertainty in medicine, we analyze the existing corpus of literature on NGS diagnostic practices. We show how in this early implementation phase of NGS, in which standardization efforts are not yet solidified, the boundary struggles around diagnoses obtained through NGS are particularly visible. We discuss the different steps in the diagnosis shaping process and what it subsequently entails to give and a receive a diagnosis using NGS. (shrink)

”This paper describes a new and innovative measure that is developed to predict workplace deviance through the measurement of Machiavellianism and Compliant Behavior. Two field studies were conducted to study the validity of the digital work simulation. In Study 1, support was found for the construct validity of the simulation. The constructs as measured with the simulation correlated significantly with self-reported measures of the constructs and were related to personality and self-esteem. Study 2 examined the criterion-related validity of the simulation (...) and showed that through the assessment of Machiavellianism the simulation was able to predict workplace deviance, and incrementally predicted organizational deviance over and above the Machiavellianism Personality Scale. Machiavellianism as measured with the simulation was less susceptible to social desirable answering compared to the Machiavellianism self-report. The paper finishes with study limitations, future research directions, and practical implications. (shrink)

Context: The dominant approach to the study of perception is representational/computational, with an emphasis on the achievements of the brain and the nervous system, which are taken to construct internal models of the world. Alternatives include ecological, embedded, embodied, and enactivist approaches, all of which emphasize the centrality of action in understanding perception. Problem: Despite sharing many theoretical commitments that lead to a rejection of the classical approach, the alternatives are characterized by important contrasts and points of divergence. Here we (...) focus on the enactive and ecological approaches, in particular, on how they construe the status of the environment and the content of perception. Method: We begin with a review of James Gibson’s ecological psychology, highlighting it as a psychology for all organisms not just humans. Against this backdrop, we consider enactivist arguments against direct perception - a central assertion of the ecological approach - and in favor of interpreting the activity of perceptual agents as a kind of construction of a perceptually meaningful world. Results: We assess the merits of this interpretation and we conclude that it cannot be grounded on fundamental principles such as thermodynamics and organism-environment mutuality. Implications: As a consequence, enactivism remains close to representationalism and entails a form of dualism. Constructivist content: We advance a criticism of the constructivist foundations of the enactive approach to perception. Perception-action mutuality at the heart of enactivism does not require mental construction; indeed, perception-action mutuality obviates construction. (shrink)

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The introduction of non-invasive prenatal testing in healthcare systems around the world offers an opportunity to reconsider funding policies for prenatal screening. In some countries with universal access healthcare systems, pregnant women and their partners are asked to pay for NIPT. In this paper, we discuss two important rationales for charging women for NIPT: to prevent increased uptake of NIPT and to promote informed choice. First, given the aim of prenatal screening, high or low uptake rates are not intrinsically desirable (...) or undesirable. Using funding policies to negatively affect uptake, however, is at odds with the aim of screening. Furthermore, copayment disproportionally affects those of lower socioeconomic status, which conflicts with justice requirements and impedes equal access to prenatal screening. Second, we argue that although payment models may influence pregnant women’s choice behaviours and perceptions of the relevance of NIPT, the copayment requirement does not necessarily lead to better-informed choices. On the contrary, external influences on women’s personal choices for or against prenatal screening should ideally be avoided. To improve informed decision-making, healthcare systems should instead invest in adequate non-directive, value-focused pretest counselling. This paper concludes that requiring copayments for NIPT in universal access healthcare systems fails to promote reproductive autonomy and is unfair. (shrink)

The phenomenon whereby severely disabled persons self-report a higher than expected level of subjective well-being is called the “disability paradox.” One explanation for the paradox among brain injury survivors is “response shift,” an adjustment of one’s values, expectations, and perspective in the aftermath of a life-altering, disabling injury. The high level of subjective well-being appears paradoxical when viewed from the perspective of the non-disabled, who presume that those with severe disabilities experience a quality of life so poor that it might (...) make their lives not worth living. This presumption has profound consequences, for it may inform end-of-life choices made in advance directives, or influence decisions made by surrogates on behalf of persons who are unable to direct their own medical treatment. -/- Peterson et al propose a cautious, well-considered plan to use fMRI-based brain-computer interfaces to assess the decision making capacity of covertly aware, behaviorally non-responsive individuals who retain high levels of preserved cognition. Their plan, if it succeeds, could eventually restore autonomy and empower some severely disabled persons, allowing them to participate in clinical decision making. Peterson et al discuss possible in-principle objections to their proposal, among them the “argument from psychological health,” and the “changing sets of values” objection. These objections both presume that deviations from a pre-injury norm could indicate diminished decision making capacity. This presumption threatens the autonomy of the patient who is capable of making decisions, but whose post-injury decisions appear to diverge from pre-injury preferences or values. In light of the potential for response shift, and the disability paradox, it should not be inferred that changes in values or preferences are unreflective of the true current preferences of a brain-injured person, nor are they conclusive evidence of diminished capacity. Presuming diminished capacity on the basis of unexpected or unconventional preferences has, in the past, been used to disempower patients whose autonomy and capacity would not have been doubted had they made choices that accorded with the expectations or values of others. We must be cautious, and vigilant, to prevent similarly diminishing the autonomy of covertly aware, behaviorally non-responsive individuals on the basis of empirically and ethically questionable inferences about their decision making capacity. (shrink)

The requirement of gauge invariance for the Schwinger-DeWitt equations, interpreted as a manifestly covariant quantum theory for the evolution of a system in spacetime, implies the existence of a five-dimensional pre-Maxwell field on the manifold of spacetime and “proper time” τ. The Maxwell theory is contained in this theory; integration of the field equations over τ restores the Maxwell equations with the usual interpretation of the sources. Following Schwinger's techniques, we study the Green's functions for the five-dimensional hyperbolic field equations (...) for both signatures ± [corresponding to O(4, 1) or O(3, 2) symmetry of the field equations] of the proper time derivative. The classification of the Green's functions follows that of the four-dimensional theory for “massive” fields, for which the “mass” squared may be positive or negative, respectively. The Green's functions for the five-dimensional field are then given by the Fourier transform over the “mass” parameter. We derive the Green's functions corresponding to the principal part ΔP and the homogeneous function Δ 1 ; all of the Green's functions can be expressed in terms of these, as for the usual field equations with definite mass. In the O(3, 2) case, the principal part function has support for x2⩾τ2, corresponding to spacelike propagation, as well as along the light cone x2=0 (for τ=0). There can be no transmission ofinformation in spacelike directions, with this propagator, since the Maxwell field, obtained by integration over τ, does not contain this component of the support. Measurements are characterized by such an integration. The spacelike field therefore can dynamically establish spacelike correlations. (shrink)

There is ongoing ethical and legal debate about withdrawing life sup- port for patients with disorders of consciousness (DOCs). Frequently fu- eling the debate are implicit assumptions about the value of life in a state of impaired consciousness, and persistent uncertainty about the quality of life (QoL) of these persons. Yet there are no validated methods for assessing QoL in this population, and a significant obstacle to doing so is their inability to communicate. Recent neuroscientific discoveries might circumvent that problem (...) and help shed light on QoL in DOCs. There is an ethical imperative to prioritize QoL research in this patient population, to provide evidence to inform treatment, research, and end of life decisions. A minimalist and pragmatic model of QoL is proposed, targeting positive and negative affect as domains for which there is po- tential to reach across the communication gap, and restore to these voiceless persons some measure of control. (shrink)

Oxford Scholarly Classics is a new series that makes available again great academic works from the archives of Oxford University Press. Reissued in uniform series design, the reissues will enable libraries, scholars, and students to gain fresh access to some of the finest scholarship of the last century.

Some people have supposed that utility is good in itself, non-in-strumentally good, as distinct from good because conducive to other good things. And in modern versions of this view, utility often means want-satisfaction, as distinct from pleasure or happiness. For your want that p to be satisfied, is it necessary that you know or believe that p, or sufficient merely that p is true? However that question is answered, there are problems with the view that want-satisfaction is a non-instrumental good. (...) What if you want something only because you have a false belief? What if the time at which you want that p is fifty or five hundred years before the time to which p itself refers? To meet these difficulties, qualifications have to be introduced, and much has been written about how exactly these qualifications are to be framed.1 There is however what may be a rather more serious objection to the view that want-satisfaction is a non-instrumental good, or rather to the combination of that view with the principle that it is sufficient for your want that p to be satisfied simply that p is true. The objection is that this combination forces you to give undue weight to the mere acquisition of desires when you come to make judgements about changes in the value of things. It forces you to say that for any true proposition p, which initially you do not want to be true, your mere acquisition of a desire that p will, other things being equal, make the world better. Non-instrumental value can be increased merely by multiplying desires, even though everything else remains the same. Surely, however, improving the world is not as easy as that. (shrink)

The Search for the Legacy of the USPHS Syphilis Study at Tuskegee is a collection of essays from experts in a variety of fields seeking to redefine the legacy of the infamous Tuskegee Syphilis Study. The essayists place the legacy of the study within the evolution of racial and ethnic relations in the United States. Contributors include two leading historians on the study, two former United States Surgeons General, and other prominent scholars from a wide range of fields.

Résumé : Le PPBS a été conçu comme un instrument destiné à ceux qui décident de l'allocation des ressources publiques : il doit leur permettre de prendre de meilleures décisions. S'il est très difficile de repérer et de juger les choix que le développement du système a inspirés aux Etats-Unis, il n'en est pas mains certain que ses résultats tangibles sant maigres car la masse des anciens programmes, principale source potentielle de moyens nouveaux, n'a guère été remise en question.La valeur (...) intrinsèque du PPBS ne peut être mise en cause. Ce qui doit l'être, c'est la lenteur de son développement, qui demeure peu avancé. Cette lenteur s'explique, car le système ne peut produire des fruits dans une terre stérile qu'on n'a pas préparée.La brutalité et les maladresses de l'opération déclenchée en 1965 dans le gouvernement fédéral américain ne pouvaient que renforcer la résistance au changement et retarder, sinon compromettre, le succès final. Les perspectives demeurent heureusement favorables, puisque la nouvelle administration ne semble pas décidée à faire machine arrière et que les Etats et Villes ont démarré sous de bien meilleurs auspices.La principale conclusion qu'imposent les expériences américaines est que toute juridiction intéressée par le PPBS doit impérativement développer, de la façon la plus générale, la volonté d'instaurer le système et s'assurer les moyens de le faire. C'est dire qu'il est peu sage d'engager la bataille sur tous les fronts à la fois : il faut tenter des percées. Mais c'est dire aussi combi en l'information et la formation sant essentielles. A cet égard, l'installation généralisée de certains éléments du système, à savoir la structure de programmes et le budget-programme, loin de présenter des inconvénients, peut constituer un excellent exercice en dehors de son utilité directe pour le preneur de décision. La bataille en cause est surtout celle de la conviction: l'outil est prêt, il est bon, encore faut-il que l' ouvrier accepte de s'en servir.Samenvatting:Planning-programming-budgeting werd ontworpen als een instrument voor diegenen die beslissen over de toewijzing van de overheidsmiddelen.Dit instrument moet de beslissers in staat stellen betere beslissingen te treffen. Het is niet makkelijk deze beslissingen op te sporen en te beoordelen welke in de Verenigde Staten getroffen werden onder invloed van de ontwikkeling van deze systeembenadering. Toch is het met vrij grote zekerheid te stellen dat de tastbare resultaten gering zijn omdat de veelheid aan oude programma's die tenslotte toch de voornaamste potentiële bronnen zijn van nieuwe middelen, nooit werden aangevochten.De intrinsieke waarde van PPBS kan daarom evenwel niet worden genegeerd. Wat wel dient aangeklaagd is de traagheid van zijn aanslepende ontwikkeling. Deze traagheid is te verklaren door het feit dat het systeem slechts vruchten kan afwerpen zo het ingeplant wordt in degelijk voorbereid terrein.De brutaliteit en de onhandigheden bij de operatie die in 1965 werd ingezet in het amerikaans federaal overheidsbestel konden niets anders dan de weerstand tegen de verandering versterken en afbreuk doen aan het uiteindelijk slagen van het systeem. Gelukkiglijk blijven de vooruitzichten gunstig want de nieuwe beleidsvoerders sinds de presidentsverkiezingen, blijken ermee te willen doorgaan en de staten en lokale overheden zijn ermee van wal gestoken onder veel betere omstandigheden. Het doorslaggevend besluit uit de amerikaanse ervaringen terzake is wel dat elke instantie welke belangstelling heeft voor PPBS, nodig moet op zo breed mogelijk vlak de wil doen groeien om het systeem te ontwikkelen en er ook de nodige middelen toe ter beschikking stellen. Dit betekent tevens dat het weinig aan te bevelen is de strijd op alle fronten terzelvertijd aan te binden maar wel geleidelijk doorbraken te verwezenlijken. Dit brengt dan evenwel ook met zich dat informatie en vorming essentieel zijn bij deze strategie. In dit verband moet dan ook gezegd worden dat reeds het invoeren van sommige deelementen van het systeem, zoals de programmastructuur en het programmabudget, voor de beslisser nuttig kan zijn voor zijn persoonlijk inzicht en vorming.De te voeren actie dient nog slechts te worden toegespitst op het overtuigen van de verantwoordelijken. Het instrument is immers gebruiksklaar en degelijk, er is alleen nog het wachten op de wil van de gebruiker dit instrument ter hand te nemen. (shrink)

Adenosine transport in cultured human umbilical vein endothelial cells (HUVEC) was characterized and shown to be mediated by a single facilitated diffusion mechanism. Initial rates of adenosine influx at 22 degrees C were saturable [apparent Michaelis constant, 69 +/- 10 mu M; maximum velocity (V-max), 600 +/- 70 pmol.10(6) cells(-1).s(-1)] and inhibited by nitrobenzylthioinosine (NBMPR). Formycin B had an unusually high affinity [inhibitory constant K-i), 18 +/- 4.3 mu M], whereas inosine had a low affinity (K-i, 440 +/- 68 mu (...) M) and nucleobases were without effect on adenosine influx. The number of transporters (1.2 x 10(6) sites/cell) was estimated by NBMPR equilibrium binding (apparent dissociation constant, 0.11 +/- 0.01 nM; maximum binding, 2.0 +/- 0.15 pmol/10(6) cells). In addition, we compared these endothelial cells with those obtained from cords from pregnancies complicated by diabetes (HUVEC-D), since embriopathy may occur in these conditions. HUVEC-D exhibited a 2.3-fold reduction in both the V-max for adenosine influx and the maximum number of NBMPR binding sites (260 +/- 40 pmol.10(6) cells(-1).s(-1) and 0.86 +/- 0.08 pmol/10(6) cells, respectively). However, the turnover number for each nucleoside transporter in normal and diabetic HUVEC was similar (approximate to 300 adenosine molecules/s). Adenosine metabolism at 10 mu M in HUVEC-D was modified compared with normal cells. Intracellular phosphorylation (> 90%) was the predominant pathway in normal HUVEC, whereas in HUVEC-D, substantial levels of adenine and adenosine were detected. The present results demonstrate therefore the downregulation of the NBMPR-sensitive nucleoside transporter and changes in adenosine metabolism in HUVEC from diabetic pregnancies. (shrink)

I Want to comment on five passages where I have provoked disagreement by a previous discussion. In the first three, my discussion was in Philologus cx , 152–4, and my critic is Bruno Gentili in Quaderni Urbinati iv , 177–81. I was not the first to make an emendation in any of the three places, so that in defending the transmitted text Gentili is actually not only criticizing me but others such as Hermann, Naeke, O. Müller, Schoemann, Hunt, Murray, and (...) Page. (shrink)

The paper is concerned with explaining some of the principal theoretical developments in elementary particle physics and discussing the associated methodological problems both in respect of heuristics and appraisal. Particular reference is made to relativistic quantum field theory, renormalization, Feynman diagram techniques, the analytic S-matrix and the Chew — Frautschi bootstrap.

The American Journal of Bioethics, Volume 11, Issue 10, Page 9-10, October 2011.

Recent discussions of experimental tests of the Sum Rule have been carried out in the context of the special circumstances attending the Cross-Ramsey experiment. A more general analysis of possible tests is presented. A technical mistake of Fine and Glymour concerned with a misunderstanding of the physics of the Cross-Ramsey experiment is explained and a detailed analysis of a thought experiment based on the Einstein-Podolsky-Rosen wave function is given. It is concluded, in agreement with Fine, that scattering experiments do not (...) test the Sum Rule as a principle which supplements standard quantum mechanics. (shrink)

In their paper, “Helpful Lessons and Cautionary Tales: How Should COVID-19 Drug Development and Access Inform Approaches to Non-Pandemic Diseases?” Holly Fernandez Lynch and colleagues have present...