The purpose of this review is to draw attention to the mechanism of dosage compensation in Drosophila as a model for the study of the regulation of gene activity through the modulation of transcription. Dosage compensation resembles some mechanisms of transcriptional regulation, found in widely divergent organisms, that do not play a role in the activation of silent genes but determine the level of activity of genes that have been induced through the action of specific activators. (...) It differs from other known regulatory mechanisms in that its effect is to achieve, on average, a twofold change in gene activity levels. This review introduces the notion that, in order to yield such a defined level of regulation, the mechanism of dosage compensation in Drosophila, and perhaps in Caenorhabditis as well, incorporates elements that govern both transcriptional enhancement and repression within the same multi‐protein regulatory complex. (shrink)

Sex chromosomes are advantageous to mammals, allowing them to adopt a genetic rather than environmental sex determination system. However, sex chromosome evolution also carries a burden, because it results in an imbalance in gene dosage between females (XX) and males (XY). This imbalance is resolved by X dosage compensation, which comprises both X chromosome inactivation and X chromosome upregulation. X dosage compensation has been well characterized in the soma, but not in the germ line. Germ (...) cells face a special challenge, because genome wide reprogramming erases epigenetic marks responsible for maintaining the X dosage compensated state. Here we explain how evolution has influenced the gene content and germ line specialization of the mammalian sex chromosomes. We discuss new research uncovering unusual X dosage compensation states in germ cells, which we postulate influence sexual dimorphisms in germ line development and cause infertility in individuals with sex chromosome aneuploidy. (shrink)

Does the three‐dimensional (3D) conformation of interphase chromosomes merely reflect their function or does it actively contribute to gene regulation? The analysis of sex chromosomes that are subject to chromosome‐wide dosage compensation processes promises new insight into this question. Chromosome conformations are dynamic and largely determined by association of distant chromosomal loci in the nuclear space or by their anchoring to the nuclear envelope, effectively generating chromatin loops. The type and extent of such interactions depend on chromatin‐bound transcription (...) regulators and therefore reflects function. Dosage compensation adjusts the overall transcription activity of X chromosomes to assure balanced expression in the two sexes. Initial analyses of mammalian and Drosophila X chromosomes have led to the hypothesis that their conformations may not only reflect their functional state but may in turn contribute to the coordination of chromosome‐wide tuning of transcription. (shrink)

Graphical AbstractMuller found halving gene dosage, as in males with one X chromosome, did not affect specific gene function. Why then was dosage “compensated?” This paradox was solved by invoking collective gene functions such as self/not self discrimination afforded by protein aggregation pressure. This predicts female susceptibility to autoimmune disease.

Mammals have a very complex, tightly controlled, and developmentally regulated process of dosage compensation. One form of the process equalizes expression of the X‐linked genes, present as a single copy in males (XY) and as two copies in females (XX), by inactivation of one of the two X‐chromosomes in females. The second form of the process leads to balanced expression between the X‐linked and autosomal genes by transcriptional upregulation of the active X in males and females. However, not (...) all X‐linked genes are absolutely balanced. This review is focused on the recent advances in studying the dosage compensation phenomenon in mammals. (shrink)

The role of RNA as a messenger in the expression of the genome has been long appreciated, but its functions in regulating chromatin and chromosome structure are no less interesting. Recent results have shown that small RNAs guide chromatin‐modifying complexes to chromosomal regions in a sequence‐specific manner to elicit transcriptional repression. However, sequence‐specific targeting by means of base pairing seems to be only one mechanism by which RNA is employed for epigenetic regulation. The focus of this review is on large (...) RNAs that act in the dosage‐compensation pathways of flies and mammals. These RNAs associate with chromatin over the length of whole chromosomes and are crucial for spreading epigenetic changes in chromatin structure. They do not appear to act in a sequence‐specific manner but might provide scaffolds for co‐operative binding of chromatin‐associated complexes that enable spreading of chromatin modifications. BioEssays 25:434–442, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

X‐chromosome inactivation ensures dosage compensation between the sexes in mammals by randomly choosing one out of the two X chromosomes in females for inactivation. This process imposes a plethora of questions: How do cells count their X chromosome number and ensure that exactly one stays active? How do they randomly choose one of two identical X chromosomes for inactivation? And how do they stably maintain this state of monoallelic expression? Here, different regulatory concepts and their plausibility are evaluated (...) in the context of theoretical studies that have investigated threshold behavior, ultrasensitivity, and bistability through mathematical modeling. It is discussed how a twofold difference between a single and a double dose of X‐linked genes might be converted to an all‐or‐nothing response and how mutually exclusive expression can be initiated and maintained. Finally, candidate factors that might mediate the proposed regulatory principles are reviewed. (shrink)

The sex chromosomes of many species differ in dosage but the total gene expression output is similar, a phenomenon referred to as dosage compensation. Previously, diverse mechanisms were postulated to account for compensation in distantly related taxa. However, two recent papers present evidence that dosage compensation in Drosophila, mammals and nematodes share the property that there is an approximately two‐fold upregulation of the single active X chromosome in each case.1,2 The results suggest that a (...) common mechanism might operate in these different cases. BioEssays 28: 565–568, 2006. © 2006 Wiley Periodicals, Inc. (shrink)

In mice, dosage compensation of X‐linked gene expression is achieved through the inactivation of one of the two X‐chromosomes in XX female cells. The complex epigenetic process leading to X‐inactivation is largely controlled by Xist and Tsix, two non‐coding genes of opposing function. Xist RNA triggers X‐inactivation by coating the inactive X, while Tsix is critical for the designation of the active X‐chromosome through cis‐repression of Xist RNA accumulation. Recently, a plethora of trans‐acting factors and cis‐regulating elements have (...) been suggested to act as key regulators of either Xist, Tsix or both; these include ubiquitous factors such as Yy1 and Ctcf, developmental proteins such as Nanog, Oct4 and Sox2, and X‐linked regulators such as Rnf12. In this paper we summarise recent advances in our knowledge of the regulation of Xist and Tsix in embryonic stem (ES) and differentiating ES cells. (shrink)

Different animal groups exhibit a surprisingly diversity of sex determination systems. Moreover, even systems that are superficially similar may utilize different underlying mechanisms. This diversity is illustrated by a comparison of sex determination in three well‐studied model organisms: the fruitfly Drosophila melanogaster, the nematode Caenorhabditis elegans, and the mouse. All three animals exhibit male heterogamety, extensive sexual dimorphism and sex chromosome dosage compensation, yet the molecular and cellular processes involved are now known to be quite unrelated. The similarities (...) must have arisen by convergent evolution. Studies of sex determination demonstrate that evolution can produce a variety of solutions to the same basic problems in development. (shrink)

In most discussions of the evolution of sex chromosomes, it is presumed that the morphological differences between the X and Y were initiated by genetic changes. An alternative possibility is that, in the early stages, a key role was played by epigenetic modifications of chromatin structure that did not depend directly on genetic changes. Such modifications could have resulted from spontaneous epimutations at a sex‐determining locus or, in mammals, from selection in females for the epigenetic silencing of imprinted regions of (...) the paternally derived sex chromosome. Other features of mammalian sex chromosomes that are easier to explain if the epigenetic dimension of chromosome evolution is considered include the relatively large number of X‐linked genes associated with human brain development, and the overrepresentation of spermatogenesis genes on the X. Both may be evolutionary consequences of dosage compensation through X‐inactivation. BioEssays 26:1327–1332, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

Mammal sex determination depends on an XY chromosome system, a gene for testis development and a means of activating the X chromosome. The duckbill platypus challenges these dogmas.1,2 Gutzner et al.1 find no recognizable SRY sequence and question whether the mammalian X was even the original sex chromosome in the platypus. Instead they suggest that the original platypus sex chromosomes were derived from the ZW chromosome system of birds and reptiles. Unraveling the puzzles of sex determination and dosage (...) class='Hi'>compensation in the platypus has been complicated by the fact that it has a surplus of sex chromosomes. Rather than a single X and Y chromosome, the male platypus has five Xs and five Ys. BioEssays 27:681–684, 2005. © 2005 Wiley Periodicals, Inc. (shrink)

X chromosome inactivation is the mammalian answer to the dilemma of dosage compensation between males and females. The study of this fascinating form of chromosome-wide gene regulation has yielded surprising insights into early development and cellular memory. In the past few months, three papers1-3 reported unexpected findings about the paternal X chromosome (Xp). All three studies agree that the Xp is imprinted to become inactive earlier than ever suspected during embryonic development. Although apparently incomplete, this early form of (...) inactivation insures dosage compensation throughout development. Silencing of the Xp persists in cells of extraembryonic tissues, but it is erased and followed by random X inactivation in cells of the embryo proper. These findings challenge several aspects of the current view of X inactivation during early development and may have profound impact on studies of pluripotency and epigenetics. BioEssays 26:821–824, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

The signal for sex determination in the nematode Caenorhabditis elegans is the ratio between the number of × chromosomes and the number of sets of autosomes (the X/A ratio). Animals with an X/A ratio of 0.67 (a triploid with two × chromosomes) or less are males. Animals with an X/A ratio of 0.75 or more are hermaphrodites. Thus, diploid males have one × chromosome and diploid hermaphrodites have two × chromosomes. However, the difference in X‐chromosome number between the sexes is (...) not reflected in general levels of X‐linked gene expression because of the phenomenon of dosage compensation. In dosage compensation, X‐linked gene expression appears to be ‘turned down’ in 2X animals to the 1X level of expression. An intriguing and unexplained finding is that mutations and X‐chromosome duplications that elevate X‐linked gene expression also feminize triploid males. One way that this relationship between sex determination and X‐linked gene expression may be operating is discussed. (shrink)

Different animal groups exhibit a surprisingly diversity of sex determination systems. Moreover, even systems that are superficially similar may utilize different underlying mechanisms. This diversity is illustrated by a comparison of sex determination in three well‐studied model organisms: the fruitfly Drosophila melanogaster, the nematode Caenorhabditis elegans, and the mouse. All three animals exhibit male heterogamety, extensive sexual dimorphism and sex chromosome dosage compensation, yet the molecular and cellular processes involved are now known to be quite unrelated. The similarities (...) must have arisen by convergent evolution. Studies of sex determination demonstrate that evolution can produce a variety of solutions to the same basic problems in development. (shrink)

Analysis of the mechanisms underlying sex determination and sex differentiation in Drosophila has provided evidence for a complex but comprehensible regulatory hierarchy governing these developmental decisions. It is suggested here that the pattern of sexual differentiation and dosage compensation characteristic of the male is a default regulatory state. Recent results have provided, in addition, some surprising and intriguing conclusions: (1) that several of the critical controlling genes produce more transcripts than was predicted from the genetic analyses; (2) that (...) setting of the alternative sex‐specific states of the doublesex (dsx) locus involves differential transcript processing; and (3) that some aspects of sexual differentation require the prolonged action of certain elements of the regulatory hierarchy. These findings are discussed in connection with the current model of sex determination in Drosophila. (shrink)

In humans over 15% of X‐linked genes have been shown to ‘escape’ from X‐chromosome inactivation (XCI): they continue to be expressed to some extent from the inactive X chromosome. Mono‐allelic expression is anticipated within a cell for genes subject to XCI, but random XCI usually results in expression of both alleles in a cell population. Using a study of allelic expression from cultured lymphoblasts and fibroblasts, many of which showed substantial skewing of XCI, we recently reported that the expression of (...) genes lies on a contiunuum between those that are subject to inactivation, and those that escape. We now review allelic expression studies from mouse, and discuss the variability in escape seen in both humans and mice in genic expression levels, between X chromosomes and between tissues. We also discuss current knowledge of the heterochromatic features, DNA elements and three‐dimensional topology of the inactive X that contribute to the balance of expression from the otherwise inactive X chromosome. (shrink)

The creeping vole Microtus oregoni exhibits remarkably transformed sex chromosome biology, with complete chromosome drive/drag, X‐Y fusions, sex reversed X complements, biased X inactivation, and X chromosome degradation. Beginning with a selfish X chromosome, I propose a series of adaptations leading to this system, each compensating for deleterious consequences of the preceding adaptation: (1) YY embryonic inviability favored evolution of a selfish feminizing X chromosome; (2) the consequent Y chromosome transmission disadvantage favored X‐Y fusion (“XP”); (3) Xist‐based silencing of Y‐derived (...) XP genes favored a second X‐Y fusion (“XM”); (4) X chromosome dosage‐related costs in XPXM males favored the evolution of XM loss during spermatogenesis; (5) X chromosomal dosage‐related costs in XM0 females favored the evolution of XM drive during oogenesis; and (6) degradation of the non‐recombining XP favored the evolution of biased X chromosome inactivation. I discuss recurrent rodent sex chromosome transformation, and selfish genes as a constructive force in evolution. (shrink)

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions. These factors include the short-term and (...) long-term effects; required medical procedures; the type of trial, including its design, therapeutic area of investigation, and dosage of the drug; the amount of compensation; and trust in the research clinic. In making determinations about the study risks, participants rely on information provided during the consent process, their own and others’ experiences in clinical trials, and comparisons among studies. Our findings indicate that the informed consent process succeeds in communicating well about certain types of risk information while simultaneously creating lacunae that are problematically filled by participants through their collective experiences and assumptions about risk. We discuss the ethical implications of these findings and make recommendations for improving the consent process in healthy volunteer trials. (shrink)

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions. These factors include the short-term and (...) long-term effects; required medical procedures; the type of trial, including its design, therapeutic area of investigation, and dosage of the drug; the amount of compensation; and trust in the research clinic. In making determinations about the study risks, participants rely on information provided during the consent process, their own and others’ experiences in clinical trials, and comparisons among studies. Our findings indicate that the informed consent process succeeds in communicating well about certain types of risk information while simultaneously creating lacunae that are problematically filled by participants through their collective experiences and assumptions about risk. We discuss the ethical implications of these findings and make recommendations for improving the consent process in healthy volunteer trials. (shrink)

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions. These factors include the short-term and (...) long-term effects; required medical procedures; the type of trial, including its design, therapeutic area of investigation, and dosage of the drug; the amount of compensation; and trust in the research clinic. In making determinations about the study risks, participants rely on information provided during the consent process, their own and others’ experiences in clinical trials, and comparisons among studies. Our findings indicate that the informed consent process succeeds in communicating well about certain types of risk information while simultaneously creating lacunae that are problematically filled by participants through their collective experiences and assumptions about risk. We discuss the ethical implications of these findings and make recommendations for improving the consent process in healthy volunteer trials. (shrink)

This article empirically examines how healthy volunteers evaluate and make sense of the risks of phase I clinical drug trials. This is an ethically important topic because healthy volunteers are exposed to risk but can gain no medical benefit from their trial participation. Based on in-depth qualitative interviews with 178 healthy volunteers enrolled in various clinical trials, we found that participants focus on myriad characteristics of clinical trials when assessing risk and making enrolment decisions. These factors include the short-term and (...) long-term effects; required medical procedures; the type of trial, including its design, therapeutic area of investigation, and dosage of the drug; the amount of compensation; and trust in the research clinic. In making determinations about the study risks, participants rely on information provided during the consent process, their own and others’ experiences in clinical trials, and comparisons among studies. Our findings indicate that the informed consent process succeeds in communicating well about certain types of risk information while simultaneously creating lacunae that are problematically filled by participants through their collective experiences and assumptions about risk. We discuss the ethical implications of these findings and make recommendations for improving the consent process in healthy volunteer trials. (shrink)

While mitigation and adaptation will help to protect us from climate change, there are harms that are beyond our ability to adapt. Some of these harms, which may have been instigated from historical emissions, plausibly give rise to duties of compensation. This chapter discusses several principles that have been discussed about how to divide climate duties—the polluter pays principle, the beneficiary pays principle, the ability to pay principle, and a new one, the polluter pays, then receives principle. The chapter (...) introduces several challenges to these principles from the literature, before discussing which policies and institutions might be relevant to compensation, whether internationally (e.g. the Green Climate Fund) or intergenerationally (e.g. Broome and Foley’s World Climate Bank). It also describes some recent successful climate cases which require both the Dutch government and a private firm to act in accordance with climate targets to avoid potential rights-violations. Finally, it discusses one of the most important international concepts with respect to compensation: the Loss & Damage pillar of climate policy. (shrink)

Many loci in Drosophila exhibit dosage effects on single phenotypes. In the case of modifiers of position‐effect variegation, increases and decreases in dosage can have opposite effects on variegating phenotypes. This is seemingly paradoxical: if each locus encodes a limiting gene product sensitive to dosage decreases, then increasing the dosage of any one should have no effect, because the others should remain limiting. An earlier model put forward to resolve this paradox suggested that dosage‐dependent modifiers (...) encode protein subunits of a macromolecular complex that is sensitive to mass action equilibrium conditions. Because chemical equilibria are dynamic, however, such hypothetical complexes will be unstable to an extent that is inconsistent with the known properties of molecules that make up chromatin. An alternative model accounts for the dosage effects in terms of interactions between structural proteins that bind at multiple linked sites. These might include indirect interactions occurring between regulatory proteins and genes for structural proteins or their protein products. The large number of direct and inverse regulatory genes which are known to exist in Drosophila could account for the apparent genetic complexity that is seen for modifiers of position‐effect variegation and for other systems of phenotypic modification. (shrink)

Can compensation repair the moral harm of a previous wrongful act? On the one hand, some define the very function of compensation as one of restoring the moral balance. On the other hand, the dominant view on compensation is that it is insufficient to fully repair moral harm unless accompanied by an act of punishment or apology. In this paper, I seek to investigate the maximal potential of compensation. Central to my argument is a distinction between (...) apologetic compensation and non-apologetic compensation. Apologetic compensation, I argue, is an act that expresses regret and apology by means of some offer of money, goods, or services. Non-apologetic compensation is an act that seeks to restore loss or harm without expressing regret or apology. In the paper, I defend the view that acts of compensation can be apologetic and argue that such apologetic compensation is sufficient for moral repair. (shrink)

ABSTRACT:If an employee is committed to his firm—if he is “attached” or “bound” to it—then his firm may be able to obtain a discount on his labor. This paper asks: Is it wrong for firms to do so? If we understand just or fair pay solely in terms of voluntary agreements between employers and employees, the answer seems to be ‘no.’ Against this, I argue that, in some cases, it is ‘yes.’ In particular, it is wrong for firms to try (...) to obtain discounts on their committed employees’ labor when their employees reasonably expect that they will not try to obtain them. In the process, I probe the limits of exploitation and question the relevance of contribution to fairness in compensation. (shrink)

This book is the first comprehensive study of the meaning and measure of enforceability. While we have long debated what restraints should govern the conduct of our social life, we have paid relatively little attention to the question of what it means to make a restraint enforceable. Focusing on the enforceability of legal rights but also addressing the enforceability of moral rights and social conventions, Mark Reiff explains how we use punishment and compensation to make restraints operative in the (...) world. After describing the various means by which restraints may be enforced, Reiff explains how the sufficiency of enforcement can be measured, and he presents a unified theory of deterrence, retribution, and compensation that shows how these aspects of enforceability are interconnected. Reiff then applies his theory of enforceability to illuminate a variety of real-world problem situations. (shrink)

It is more or less uncontroversial that when we harm someone through wrongful conduct we incur an obligation to compensate her. But sometimes compensation is impossible: when the victim is killed, for example. Other times, only partial compensation is possible. In this article, I take some initial steps towards exploring this largely ignored issue. I argue that the perpetrator of a wrongful harm incurs a duty to promote the impartial good in proportion to the amount of harm that (...) cannot be made up for by compensating her victim. (shrink)

Even in just wars we infringe the rights of countless civilians whose ruination enables us to protect our own rights. These civilians are owed compensation, even in cases where the collateral harms they suffer satisfy the proportionality constraint. I argue that those who authorize or commit the infringements and who also benefit from those harms will bear that compensatory duty, even if the unjust aggressor cannot or will not discharge that duty. I argue further that if we suspect antecedently (...) that we will culpably refrain from compensating those victims post bellum, then this makes satisfying the war’s proportionality constraint substantially more difficult at the outset of the war. The lesson here is that failing to take duties of compensation in war seriously constrains our moral permission to protect ourselves. (shrink)

In this article, we deal with the evaluation of the losses suffered by persons living in urban areas as a result of energy services. In the first part, we analyse how by adopting different informational foci we obtain contrasting interpersonal evaluations regarding the same loss. In the second part, we distinguish between a diachronic and a hypothetical/moralised threshold for harm in order to assess whether individuals are benefiting from or being harmed by a given energy service. Our argument is that (...) the most accurate evaluation of an individual damage caused by an energy service can be obtained by using capabilities as informational focus, instead of realised wellbeing or means to wellbeing, and by interpreting the loss in relation to a hypothetical/moralised threshold that corresponds to a list of central capabilities. In the last part, we address monetary and non-monetary compensations for a loss that is evaluated in terms of capabilities. Accordingly, we expound how compensation policies can either restore the capabilities lost due to energy services or monetarily compensate the individual for the fact that a given capability (or set of capabilities) has been irremediably lost. (shrink)

Surrogate motherhood is treated as a form of adoption in many countries: the birth mother and her partner are presumed to be the parents of the child, while the intended parents have to adopt the baby once it is born. Other than compensation for expenses related to the pregnancy, payment to surrogates is not permitted. We believe that the failure to compensate surrogate mothers for their labour as well as the significant risks they undertake is both unfair and exploitative. (...) We accept that introducing payment for surrogates would create a significant tension in the adoption model. However, we recommend rejecting the adoption model altogether rather than continuing to prohibit compensation to surrogates. (shrink)

This paper examines whether the prospect of compensation may render otherwise disproportionate harms proportionate. It argues that we should reject this possibility. Instead, it distinguishes duties of compensation as a requirement of rectificatory justice from a harm’s degree of compensability, and argues that only the latter is relevant to proportionality. On this view, failing to compensate constitutes a distinct wrong, while harms that are not adequately compensable carry extra weight in proportionality calculations. This explains how the prospect of (...) compensation affects permissions to harm, without relying on the dubious assumption that disproportionate harms may be rendered proportionate by future compensation. (shrink)

Calls for compensation are heard in many countries all over the world. Spokespersons on behalf of formerly oppressed and dominated groups call for compensation for the deeply traumatic injustices their members have suffered in the past. Sometimes these injustices were suffered decades ago by members already deceased. How valid are such claims to compensation and should they be honoured as a matter of justice? The focus of this essay is on these issues of compensatory justice. I want (...) to look at the issue from the perspective of the eradication of systematic poverty affecting particular groups—where injustices of the distant past can reliably be identified as one of the major contributory factors to people’s current poverty. In the paper I will examine the following issues: (1) What kind of injustices qualify to be remedied by means of compensatory justice? (2) Should there be a limit to how far back in history one should go to compensate for injustice? (3) How can an injustice from the distant past be reliably identified as a cause of current problems? (4) Who should be compensated? (5) Who is responsible for compensation? (6) What form should compensation take? (7) Is the concept of compensatory justice backward looking or forward looking? I will argue for a moral obligation to the effect that serious injustices, perpetrated long ago against a group of people and caused them to be poor, ought to be compensated by society in a variety of ways to the original victims (if still alive) and their descendants. (shrink)

It is sometimes morally permissible not to help others even when doing so is overall better for you. For example, you are not morally required to take a career in medicine over a career in music, even if the former is both better for others and better for you. I argue that the permissibility of not helping in a range of cases of “compensated altruism” is explained by the existence of autonomy-based considerations. I sketch a view according to which you (...) can have autonomy-based permissions to choose between alternatives when these alternatives differ in terms of the valuable features they instantiate. Along the way, I argue that considerations of moral autonomy do not support rejecting the plausible view that we each constantly face reasons with morally requiring strength to help (distant) strangers. (shrink)

This thesis considers two allegations which conservatives often level at no-fault systems — namely, that responsibility is abnegated under no-fault systems, and that no-fault systems under- and over-compensate. I argue that although each of these allegations can be satisfactorily met – the responsibility allegation rests on the mistaken assumption that to properly take responsibility for our actions we must accept liability for those losses for which we are causally responsible; and the compensation allegation rests on the mistaken assumption that (...) tort law’s compensatory decisions provide a legitimate norm against which no-fault’s decisions can be compared and criticized – doing so leads in a direction which is at odds with accident law reform advocates’ typical recommendations. On my account, accident law should not just be reformed in line with no-fault’s principles, but rather it should be completely abandoned since the principles that protect no- fault systems from the conservatives’ two allegations are incompatible with retaining the category of accident law, they entail that no-fault systems are a form of social welfare and not accident law systems, and that under these systems serious deprivation – and to a lesser extent causal responsibility – should be conditions of eligibility to claim benefits. (shrink)

The historical-cultural theory of Intellectual Disability overcompensation/compensation is referenced in several studies, but little empirical evidence is presented to corroborate this thesis. In this work, 13 current studies were analysed about the behavioural profile of people with Down syndrome, a case of neurobiological ID, published in the last 15 years, in order to verify the possibility of dialogue with the theorizing about compensation. Despite contributing to an up to date understanding of DS, the results point to similarities between (...) different scientific traditions allowing discussions regarding methodologies, data interpretation, language comprehension, and the impact of the studies for school inclusion and the development of people with ID/DS. It is concluded that the theorization in question is pertinent to developmental studies, dialogues with other perspectives and that its progress depends on investigations directed to the affective motivators/emotions of the person with ID/DS by means of more interpretative methodologies. Keywords: Down syndrome, compensation, behavioural profile, Intellectual Disabilities Development. (shrink)

RésuméLe dosage de traces de molécules organiques dans les matrices biologiques fait appel à des techniques analytiques physico‐chimiques dont la chromatographie en phase gazeuse couplée à la spectrumétrie de masse est une des plus puissantes. Des possibilityés nouvelles pour augmenter la sensibilityé de la détection de ces substances sont presentees et mises en relation avec la signification physiologique des résultats obtenus.SummaryGas chromatography‐mass spectrometry is the method of choice for the quantitative determination of organic traces in biological systems. New technical (...) developments allow higher sensitivity and greater specificity which are discussed together with the physiological meaning of the data thus obtained.ZusammenfassungDie Dosierung der Spuren von organischen Molekülen in den biologischen Matrizen erfordert physico‐chemische analytische Techniken, deren Chromatographie in gasförmiger Phase ver‐bunden mit der Massenspektrometrie eine der mächtigsten ist. Es werden neue Möglichkeiten zur Steigerung der Empfindlichkeit der Aufweisung dieser Substanzen vorgelegt, und mit der physio‐logischen Bedeutung der erhaltenen Ergebnisse in Beziehung gesetzt. (shrink)

Compensation and reparation are two parts or forms of compensatory or corrective justice. This essay aims, first, to distinguish, define, and analyze these two forms as against distributive and penal justice; and, second, to provide a moral justification of a system or social practice of compensation and of reparation, drawing on the ideas of Aristotle, William Blackstone, Bernard Boxill, John Rawls, and James Sterba. Then, by applying the results of the analysis to the first genocide of the twentieth (...) century, the Armenian genocide, it illustrates certain difficulties in realizing reparative justice when the wrongful injury is perpetrated by a sovereign state, and it emphasizes the paramount importance in such cases of the acknowledgment of wrong by the perpetrator. (shrink)

While geoengineering may counteract negative effects of anthropogenic climate change, it is clear that most geoengineering options could also have some harmful effects. Moreover, it is predicted that the benefits and harms of geoengineering will be distributed unevenly in different parts of the world and to future generations, which raises serious questions of justice. It has been suggested that a compensation scheme to redress geoengineering harms is needed for geoengineering to be ethically and politically acceptable. Discussions of compensation (...) for geoengineering harms, however, sometimes presume geoengineering has presented new and unique challenges to compensation that cannot be readily accommodated by existing compensation practices. The most explicit formulation of this view was recently presented by Toby Svoboda and Peter J. Irvine, who argued that two forms of uncertainty in geoengineering — namely, ethical uncertainty and scientific uncertainty — make it immensely difficult to devise an ethically and politically satisfactory compensation scheme for geoengineering harms. -/- In this paper, we argue against the view that geoengineering presents new and unique challenges relating to compensation. More specifically, we show that placing these challenges within the broader context of anthropogenic climate change reveals them to be less serious and less specific to geoengineering than some appear to believe. (shrink)

The COVID-19 pandemic has created unusually challenging and dangerous workplace conditions for key workers. This has prompted calls for key workers to receive a variety of special benefits over and above their normal pay. Here, we consider whether two such benefits are justified: a no-fault compensation scheme for harm caused by an epidemic and hazard pay for the risks and burdens of working during an epidemic. Both forms of benefit are often made available to members of the armed forces (...) for the harms, risks and burdens that come with military service. We argue from analogy that these benefits also ought to be provided to key workers during an epidemic because, like the military, key workers face unavoidable harms, risks and burdens in providing essential public good. The amount of compensation should be proportional to the harm suffered and the amount of hazard pay should be proportional to the risk and burden endured. Therefore, key workers should receive the same amount of compensation and hazard pay as the military where the harms, risks and burdens are equivalent. In the UK, a form of no-fault compensation has recently been made available to the surviving families of key workers who suffer fatal COVID-19 infections. According to our argument, however, it is insufficient because it offers less to key workers than is made available to the families of armed services personnel killed on duty. (shrink)

A natural way of viewing compensation is to see it as the restoration of a good or level of well-being which someone would have enjoyed if he had not been adversely affected by the act of another. This view underlies Nozick’s assertion that “something fully compensates … person X for Y’s action A if X is no worse off receiving it, Y having done A, than X would have been without receiving it if Y had not done A”; and (...) it has been held by many others as well. Because the notion that compensation is the restoration of a good which a person would have had but for the act of another is so pervasive, I shall refer to it as the official view of compensation. One noteworthy feature of the official view is the ease with which it allows compensation to be justified in particular cases. If compensation is just the restoration of a good which one would have had if the ordinary course of things had not been disrupted, then to provide a prima facie justification of it, one need only argue that the natural course of things should not have been disrupted in the first place. (shrink)

In March 2010, China launched a pilot programme of deceased donor organ donation in 10 provinces and cities. However, the deceased donor donation rate in China remains significantly lower than in Spain and other Western countries. In order to provide incentive for deceased donor organ donation, five pilot provinces and cities have subsequently launched a financial compensation policy. Financial compensation can be considered to include two main forms, the ‘thank you’ form and the ‘help’ form. The ‘thank you’ (...) form is an expression of gratitude on behalf of the Red Cross Society of China for consenting to donation. The ‘help’ form is social welfare support for needy families. (shrink)

It could be argued that tort law is failing, and arguably an example of this failure is the recent public liability and insurance (‘PL&I’) crisis. A number of solutions have been proposed, but ultimately the chosen solution should address whatever we take to be the cause of this failure. On one account, the PL&I crisis is a result of an unwarranted expansion of the scope of tort law. Proponents of this position sometimes argue that the duty of care owed by (...) defendants to plaintiffs has expanded beyond reasonable levels, such that parties who were not really responsible for another’s misfortune are successfully sued, while those who really were to blame get away without taking any responsibility. However people should take responsibility for their actions, and the only likely consequence of allowing them to shirk it is that they and others will be less likely to exercise due care in the future, since the deterrents of liability and of no compensation for accidentally self-imposed losses will not be there. Others also argue that this expansion is not warranted because it is inappropriately fueled by ‘deep pocket’ considerations rather than by considerations of fault. They argue that the presence of liability insurance sways the judiciary to award damages against defendants since they know that insurers, and not the defendant personally, will pay for it in the end anyway. But although it may seem that no real person has to bear these burdens when they are imposed onto insurers, in reality all of society bears them collectively when insurers are forced to hike their premiums to cover these increasing damages payments. In any case, it seems unfair to force insurers to cover these costs simply because they can afford to do so. If such an expansion is indeed the cause of the PL&I crisis, then a contraction of the scope of tort liability, and a pious return to the fault principle, might remedy the situation. However it could also be argued that inadequate deterrence is the cause of this crisis. On this account the problem would lie not with the tort system’s continued unwarranted expansion, but in the fact that defendants really have been too careless. If prospective injurers were appropriately deterred from engaging in unnecessarily risky activities, then fewer accidents would ever occur in the first place, and this would reduce the need for litigation at its very source. If we take this to be the cause of tort law’s failure then our solution should aim to improve deterrence. Glen Robinson has argued that improved deterrence could be achieved if plaintiffs were allowed to sue defendants for wrongful exposure to ongoing risks of future harm, even in the absence of currently materialized losses. He argues that at least in toxic injury type cases the tortious creation of risk [should be seen as] an appropriate basis of liability, with damages being assessed according to the value of the risk, as an alternative to forcing risk victims to abide the outcome of the event and seek damages only if and when harm materializes. In a sense, Robinson wishes to treat newly-acquired wrongful risks as de-facto wrongful losses, and these are what would be compensated in liability for risk creation (‘LFRC’) cases. Robinson argues that if the extent of damages were fixed to the extent of risk exposure, all detected unreasonable risk creators would be forced to bear the costs of their activities, rather than only those who could be found responsible for another’s injuries ‘on the balance of probabilities’. The incidence of accidents should decrease as a result of improved deterrence, reduce the ‘suing fest’, and so resolve the PL&I crisis. So whilst the first solution involves contracting the scope of tort liability, Robinson’s solution involves an expansion of its scope. However Robinson acknowledges that LFRC seems prima facie incompatible with current tort principles which in the least require the presence of plaintiff losses, defendant fault, and causation to be established before making defendants liable for plaintiffs’ compensation. Since losses would be absent in LFRC cases by definition, the first evidentiary requirement would always be frustrated, and in its absence proof of defendant fault and causation would also seem scant. If such an expansion of tort liability were not supported by current tort principles then it would be no better than proposals to switch accident law across to no-fault, since both solutions would require comprehensive legal reform. However Robinson argues that the above three evidentiary requirements could be met in LFRC cases to the same extent that they are met in other currently accepted cases, and hence that his solution would therefore be preferable to no-fault solutions as it would only require incremental but not comprehensive legal reform. Although I believe that actual losses should be present before allowing plaintiffs to seek compensation, I will not present a positive argument for this conclusion. My aim in this paper is not to debate the relative merits of Robinson’s solution as compared to no-fault solutions, nor to determine which account of the cause of the PL&I crisis is closer to the truth, but rather to find out whether Robinson’s solution would indeed require less radical legal reform than, for example, proposed no-fault solutions. I will argue that Robinson fails to show that current tort principles would support his proposed solution, and hence that his solution is at best on an even footing with no-fault solutions since both would require comprehensive legal reform. (shrink)

Currently living people cannot be said to be wronged because of the wrongless emissons of greenhouse gases by past people. According to the usual subjunctive-historical understanding of harm, currently living people cannot be said to be harmed by the impact of greenhouse emissions on their well-being. By relying on a subjunctive-threshold notion of harm we can justify conclusions about both the present generation’s duties not to violate the rights of future generations, and the present generation’s duties to compensate currently living (...) people for the harms inflicted upon them through the lasting impact of wrongless past harms. This interpretation supports a forward-looking understanding of the grounds of our relating to wrongless past harms. The significance of past harms lies in their consequences for the well-being of currently living and future people. The subjunctive-threshold notion of harm lends support to a standard of minimal, general, and universal justice. Those actors who are in a position to fulfill its requirements are under a duty to do so. Especially the rich and powerful countries ought to counteract the harmful impact of past greenhouse emissions. (shrink)

Background Compensating participants of biomedical research is a common practice. However, its proximity with ethical concerns of coercion, undue influence, and exploitation, demand that participant compensation be regulated. The objective of this paper is to discuss the current regulations for compensation of research participants in Malawi and how they can be improved in relation to ethical concerns of coercion, undue influence, and exploitation. Main text In Malawi, national regulations recommend that research subjects be compensated with a stipend of (...) US$10 per study visit. However, no guidance is provided on how this figure was determined and how it should be implemented. While necessary to prevent exploitation, the stipend may expose the very poor to undue influence. The stipend may also raise the cost of doing research disadvantaging local researchers and may have implications on studies where income stipend is the intervention under investigation. We recommend that development and implementation of guidelines of this importance involve interested parties such as the research community and patient groups. Conclusion Compensating human research subjects is important but can also act as a barrier to voluntary participation and good research efforts. Deliberate measures need to be put in place to ensure fair compensation of research participants, avoid their exploitation and level the field for locally funded research. (shrink)

Compensation for research related injuries is a subject that is increasingly gaining traction in developing countries which are burgeoning destinations of multi center research. However, the existence of disparate compensation rules violates the ethical principle of fairness. The current paper presents a comparison of the policies of Brazil, Russia, India, China and South Africa. A systematic search of good clinical practice guidelines was conducted employing search strategies modeled in line with the recommendations of ADPTE Collaboration. The search focused (...) on three main areas namely bibliographic data bases, clinical practice guidelines data bases and a restricted internet search. A manual search of references cited in relevant guideline documents was also conducted. The search terms, Medical Subject Headings and key words were developed for a PubMed platform and then adapted for all other data bases. The search terms were kept constant for each country with the only difference being the country name. The documents so obtained were subjected to systematic content analysis. The study revealed that there is vast panoply of regulations which exist on a continuum. On one extreme is India with comprehensive regulations that are codified into law, and on the other end there is China which does not have specific laws regulating research related injuries. There are a number of differences and similarities such as mandatory insurance requirements, existence of no fault compensation, compensable injuries and the role of research ethics committees. It is imperative to enact legislations that protect participants without stifling the research enterprise. There is need for consistency and ideally harmonization of such regulations at a global level. A model policy on compensation for research related injuries should borrow from the best aspects of the different country policies and should be informed by the cardinal ethics principles of autonomy, justice and beneficence. (shrink)