I. EXECUTIVE SUMMARY The MRCT Center Post-trial Responsibilities: Continued Access to an Investigational Medicine Framework outlines a case-based, principled, stakeholder approach to evaluate and guide ethical responsibilities to provide continued access to an investigational medicine at the conclusion of a patient’s participation in a clinical trial. The Post-trial Responsibilities (PTR) Framework includes this Guidance Document as well as the accompanying Toolkit. A 41-member international multi-stakeholder Workgroup convened by the Multi-Regional Clinical Trials Center of Brigham and Women’s Hospital and Harvard University (...) (MRCT Center) developed this Guidance and Toolkit. Project Motivation A number of international organizations have discussed the responsibilities stakeholders have to provide continued access to investigational medicines. The World Medical Association, for example, addressed post-trial access to medicines in Paragraph 34 of the Declaration of Helsinki (WMA, 2013): “In advance of a clinical trial, sponsors, researchers and host country governments should make provisions for post-trial access for all participants who still need an intervention identified as beneficial in the trial. This information must also be disclosed to participants during the informed consent process.” This paragraph and other international guidance documents converge on several consensus points: • Post-trial access (hereafter referred to as “continued access” in this Framework [for terminology clarification – see definitions]) is the responsibility of sponsors, researchers, and host country governments; • The plan for continued access should be determined before the trial begins, and before any individual gives their informed consent; • The protocol should delineate continued access plans; and • The plan should be transparent to potential participants and explained during the informed consent process. -/- However, there is no guidance on how to fulfill these responsibilities (i.e., linking specific responsibilities with specific stakeholders, conditions, and duration). To fill this gap, the MRCT Center convened a working group in September of 2014 to develop a framework to guide stakeholders with identified responsibilities. This resultant Framework sets forth applicable principles, approaches, recommendations and ethical rationales for PTR regarding continued access to investigational medicines for research participants. (shrink)

Progressive supranuclear palsy is a movement disorder with prominent tau neuropathology. Brain diseases with abnormal tau deposits are called tauopathies, the most common of which is Alzheimer's disease. Environmental causes of tauopathies include repetitive head trauma associated with some sports. To identify common genetic variation contributing to risk for tauopathies, we carried out a genome-wide association study of 1,114 individuals with PSP and 3,247 controls followed by a second stage in which we genotyped 1,051 cases and 3,560 controls for the (...) stage 1 SNPs that yielded P ≤ 10-3. We found significant previously unidentified signals associated with PSP risk at STX6, EIF2AK3 and MOBP. We confirmed two independent variants in MAPT affecting risk for PSP, one of which influences MAPT brain expression. The genes implicated encode proteins for vesicle-membrane fusion at the Golgi-endosomal interface, for the endoplasmic reticulum unfolded protein response and for a myelin structural component. © 2011 Nature America, Inc. All rights reserved. (shrink)

We will look at several theories of indicative conditionals grouped into three categories: those that base its semantics on its logical counterpart (the material conditional); intensional analyses, which bring in alternative possible worlds; and a third subgroup which denies that indicative conditionals express propositions at all. We will also look at some problems for each kind of approach.

Essays by Jurgen Habermas on truth, objectivity, normativity, naturalism, and realism after the linguistic turn.

SummaryCross-sectional studies in Australia and the Philippines and a longitudinal prospective study in a selected Australian sample of breast-feeding mothers have shown that basal serum prolactin concentrations are elevated during 15–21 months of lactational amenorrhoea.A predictive model of serum PRL levels and return of cyclic ovarian activity during full breast-feeding, partial breast-feeding and weaning has been developed from the results of breast-feeding behaviour and serum PRL, gonadotrophin and oestradiol measurements in 34 mothers breast-feeding on demand for a mean of 67 (...) weeks.Breast-feeding patterns influence serum PRL levels. Important factors during full breast-feeding are the age of the baby, the longest interval between feeds at night and total 24-hr suckling time, and following the introduction of supplements, the mean interval between feeds, together with the total 24-hr suckling time and the number of solid supplements per day.The precise mechanisms whereby breast-feeding regulates cyclic ovarian activity remain unknown. Gonadotrophin secretion appears to be quantitatively normal, but qualitative changes, secondary to altered hypothalamic activity, may be the most important factor. A direct inhibitory effect of PRL on ovarian follicular development and steroidogenesis remains possible.Ovulation with a normal luteal phase is probable for 30% of breast-feeding mothers before the first menses, but is unlikely before 6 months, provided breast-feeding is frequent day and night.Measurement of serum PRL is a sensitive index of the return of menstruation and fertility during lactation in the population studied. (shrink)

This collection breaks new ground in four key areas of feminist social thought: the sex/gender debates; challenges to liberalism/equality; feminist ethics; and feminist perspectives on global ethics and politics in the 21st century. Altogether, the essays provide an innovative look at feminist philosophy while making substantive contributions to current debates in gender theory, ethics, and political thought.

Evolutionary models consider hunting and food sharing to be milestones that paved the way from primate to human societies. Because fossil evidence is scarce, hominoid primates serve as referential models to assess our common ancestors’ capacity in terms of communal use of resources, food sharing, and other forms of cooperation. Whereas chimpanzees form male-male bonds exhibiting resource-defense polygyny with intolerance and aggression toward nonresidents, bonobos form male-female and female-female bonds resulting in relaxed relations with neighboring groups. Here we report the (...) first known case of meat sharing between members of two bonobo communities, revealing a new dimension of social tolerance in this species. This observation testifies to the behavioral plasticity that exists in the two Pan species and contributes to scenarios concerning the traits of the last common ancestor of Pan and Homo. It also contributes to the discussion of physiological triggers of in-group/out-group behavior and allows reconsideration of the emergence of social norms in prehuman societies. (shrink)

Empirical studies show that though there is more room for improvement, much progress has been made toward gender equality since the second wave of feminism. Evidence also suggests that women’s advancements have been more dramatic in the public sphere of work and politics than in the private sphere of family life. We argue that this lopsided gender progress may be traced to uneven changes in gender attitudes. Using data from more than 27,000 respondents who participated in the General Social Survey (...) from 1977 through 2016, we show that gender attitudes have more than one underlying dimension and that these dimensions have changed at different rates over time. Using latent class analysis, we find that the distribution of respondents’ attitudes toward gender equality has changed over the past 40 years. There has been an increase in the number of egalitarians who support equality in public and private spheres, while the traditionals who historically opposed equality in both domains have been replaced by ambivalents who feel differently about gender equality in the public and private spheres. Meanwhile, successive birth cohorts are becoming more egalitarian, with Generation-Xers and Millennials being the most likely to hold strong egalitarian views. The feminist revolution has succeeded in promoting egalitarian views and decreasing the influence of gender traditionalism, but has yet to convince a substantial minority that gender equality should extend to both public and private spheres of social life. (shrink)

The paper considers the legal tools that have been developed in German pharmaceutical regulation as a result of the precautionary attitude inaugurated by the Contergan decision. These tools are the notion of “well-founded suspicion”, which attenuates the requirements for safety intervention by relaxing the requirement of a proved causal connection between danger and source, and the introduction of the reversal of proof burden in liability norms. The paper focuses on the first and proposes seeing the precautionary principle as an instance (...) of the requirement that one should maximise expected utility. In order to maximise expected utility certain probabilities are required and it is argued that objective Bayesianism offers the most plausible means to determine the optimal decision in cases where evidence supports diverging choices. (shrink)

In 1960, a relatively new ‘syndrome’ began appearing with growing frequency in psychiatric hospitals and in doctors’ offices. Eventually termed ‘delicate self-cutting’, this new model for typical self-mutilative behavior was developed in conjunction with a description of the ‘typical’ self-mutilator: young (adolescent to just post-adolescent), female, and almost always attractive. This article contends that, despite recent efforts to change the nature of research on self-mutilation, the myth of a typical mutilator, developed from a particular historical bias, continues to work in (...) popular and medical discourses on the subject. I will begin with a detailed discussion of the medical discourse in an effort to ask how the myth was made. Noting that the female body, here, is singled out as pathological at a time when, specifically in the USA, the emergent Women’s Movement was beginning to contest certain gender lines, I would like to examine how the medical discourse and material bodies interrelate and interact with each other and with the cultural narratives around them. Finally, I end with examples from the 1999 film Girl, Interrupted, as well as other recent popular and medical accounts, to illustrate not only the perpetuation of the myth of the ‘typical’ self-mutilator but also the inability or refusal to recognize the biased nature of the medical discourse in the instance on self-mutilation. (shrink)

According to Hume, experience in observing art is one of the prerequisites for being an ideal art critic. But although Hume extols the value of observing art for the art critic, he says little about the value, for the art critic, of executing art. That is, he does not discuss whether ideal aesthetic judges should have practiced creating the form of art they are judging. In this paper, I address this issue. Contrary to some contemporary philosophers who claim that experience (...) in creating art is irrelevant to one’s ability to judge that art form, as well as to some dance critics who see dance training as possibly even detrimental to one’s aesthetic judgment, I suggest that having practiced dancing makes one a better observer of certain aesthetic qualities of dance. Dance training, I argue, can facilitate a kinesthetic experience upon watching dance without which some aesthetic aspects of a dance performance—such as grace, power, and precision, as perceived kinesthetically—may go unnoticed. (shrink)

This paper examines nurses’ international migration within the broader context of female migration, particularly against more studied groups of women who have migrated for employment in care‐giving roles. We analyze the similarities and differences between skilled professional female migrants (nurses) and domestic workers (nannies and in‐home caretakers) and how societal expectations, meanings, and values of care and ‘women's work’, together with myriad social, cultural, economic and political processes, construct the female migrant care‐giver experience. We argue that, as the recruitment of (...) foreign workers gains visibility, strategies are introduced to better prepare female migrant care‐givers for the marketplace. Language, specifically command of English and accent modification, is highlighted as one means to assimilate migrant care‐givers to host communities. (shrink)

Everyone agrees that law is a constituent of social reality. Law seems to be a system by which conduct is governed and guided. Its usefulness consists, in part, on its ability to govern and guide conduct in its characteristic way. If laws guides the conduct of lay law subjects, then it must be (really) possible for the content of the laws governing their conduct to be known by them under standard social conditions. Moreover, if some degree of efficacy in guiding (...) and governing the conduct of lay law subjects is an existence condition for a legal system, then in existing legal systems enough of the content of directive law is epistemically accessed by enough law subjects so that they can apply it to their situations and correctly determine the act-tokens required of them. In this chapter, I argue that these modest epistemic reflections have important implications for a theory of legal content that have been largely ignored. Holistic theories of legal content, such as Greenberg’s and Dworkin’s, are inconsistent with an adequate account of epistemic access. After demonstrating the same problem in two mainstream non-holistic theories of legal content -- the view that legal content is set entirely by official interpretive conventions, and the view that legal content is set entirely by official intentions – I propose a theory of legal content that meets the epistemic access challenge. On my approach, law is, at its core, centered upon the understandings of law subjects. (This view is meant to exempt constitutional provisions.) More precisely, the legal content of statutes and judicial decisions is built around, and preserves, a core of understandings and meaning-assignments that is the province of anyone with sufficient linguistic ability and relevant socialization. The details of this view are, roughly: (1) in the case of judicial decisions in a common law system, the social salience of the example the decision sets concerning behavior sets the default legal content; (2) in the case of statutory directives, the set of socially salient applications (behavior in situations) sets the default legal content. I say `default’ because my account of legal content is a two-stage account beginning with the default content and permitting a second stage in which considerations from other sources can operate on the default. Yet if a certain amount of efficacy in guiding lay law subjects’ behavior is a requirement for the existence of a legal system, there must be a core of legal content undistorted from its default social salience by a second stage operation. There is and must be a `law of the street’. -/- . (shrink)

We investigate the complexity of isomorphisms of computable structures on cones in the Turing degrees. We show that, on a cone, every structure has a strong degree of categoricity, and that degree of categoricity is${\rm{\Delta }}_\alpha ^0 $-complete for someα. To prove this, we extend Montalbán’sη-system framework to deal with limit ordinals in a more general way. We also show that, for any fixed computable structure, there is an ordinalαand a cone in the Turing degrees such that the exact complexity (...) of computing an isomorphism between the given structure and another copy${\cal B}$in the cone is a c.e. degree in${\rm{\Delta }}_\alpha ^0\left$. In each of our theorems the cone in question is clearly described in the beginning of the proof, so it is easy to see how the theorems can be viewed as general theorems with certain effectiveness conditions. (shrink)

Contemporary organizations often reciprocate to society for using resources and for affecting stakeholders by engaging in corporate social responsibility. It has been shown that CSR has a positive impact on employee attitudes. However, not all employees may react equally strongly to CSR practices. Based on socio-emotional selectivity theory, we contend that the effect of CSR on employee satisfaction will be more pronounced for older than for younger employees, because CSR practices address those emotional needs and goals that are prioritized when (...) people’s future time perspective decreases. In one multi-source field study and one experimental study, we demonstrate that CSR indeed has a stronger positive effect on employee satisfaction for older relative to younger employees. Accordingly, engaging in CSR can be an attractive tool for organizations that aim to keep their aging workforce satisfied with their job. (shrink)

Imagine that our world were such that the entities, properties, laws, and relations of fundamental physics did not determine what goes on at the mental level; imagine that duplicating our fundamental physics would fail to duplicate the pleasures, feelings of joy, and experiences of wonder that we know and love; in other words, imagine that the mental realm did not supervene on the physical realm. Would our world, then, be a world in which physicalism is false? A good number of (...) philosophers who ponder such issues—perhaps all philosophers who have hitherto pondered such issues—answer “yes.” The purpose of this paper is to suggest that, despite what physicalists say, they don’t think so, either. What is it that they really think? What is the actual doctrine of physicalism? I conclude withan attempt to uncover that as well. (shrink)

The essay examines the impact of thought insertion on typical conceptions of self-consciousness. Stephens and Graham have recently argued that thought insertion is compatible with the inseparability thesis, which maintains that with regard to self-consciousness subjectivity is a proper part of introspection--introspection and subjectivity are inseparable. They argue that thought insertion is an error of agency and not an error of subjectivity. The essay contends that even if they are correct in their interpretation that thought insertion is an error of (...) agency rather than subjectivity, which is unlikely, they are incorrect to maintain that it is not also an error of subjectivity. Evidence is put forth to indicate that thought insertion is, at best, a mistake of agency and subjectivity. It is concluded that thought insertion is incompatible with the inseparability thesis, and a new inseparability thesis is thereby postulated. (shrink)

Prenatal screening and testing are preference‐based health care options. They are offered so that pregnant women and their partners can learn genetic information about the developing fetus. In this literature review, I summarize studies of women’s and their partners’ psychological responses to prenatal testing and screening. These studies investigate the experiences of pregnant women, largely in the United States, who have access to health care services. Although the results indicate that these women are receptive to prenatal testing and screening and (...) seem to have limited negative psychological consequences, pregnant women without access to these services are not represented and may have different experiences. With that caveat in mind, based on the evidence, women generally do well psychologically as they manage the options that arise for them in the prenatal context. (shrink)

We show that Sacks' and Shoenfield's analogs of jump inversion fail for both tt- and wtt-reducibilities in a strong way. In particular we show that there is a ${\mathrm{\Delta }}_{2}^{0}$ set B > tt ∅′ such that there is no c.e. set A with A′ ≡ wtt B. We also show that there is a ${\mathrm{\Sigma }}_{2}^{0}$ set C > tt ∅′ such that there is no ${\mathrm{\Delta }}_{2}^{0}$ set D with D′ ≡ wtt C.

In early work within Conversation Analysis, utterances within a request sequence which inquire regarding some of the preconditions of granting the request are analyzed as pre-requests. Levinson, in an extended discussion of the organization of pre-requests and request sequences, treats utterances such as ‘do you have X?’, ‘can I have X?’ or ‘can you X for me?’ as inquiring about preconditions that could prevent the recipient from granting the request. By checking on preconditions, the requester works to avoid producing a (...) request which will be declined, which is a dispreferred action. In other words, pre-requests, like other pre-sequences, function to project that another action will be produced if a favorable response is given; if not, that projected action may not be produced. In this view, then, they work to maintain the preference organization. This study uses requesting in service encounters to re-examine the evidence for an analysis of such utterances as pre-requests and finds that alternative analyses are more suited in these requesting activities. (shrink)

Not at all self-evident, the so-called isomorphisms between the phenomenology and physiology of dreams have been interpreted by Hobson et al. in an arbitrary manner to state that dreams are stimulated by chaotic brainstem stimulation (an assumption also adopted by Vertes & Eastman). I argue that this stimulation is not chaotic at all; nor does it occur in the absence of control from the cerebral cortex, which contributes complexity to brainstem activity as well as meaningful information worth consolidating in the (...) brain during sleep. [Hobson et al.; Vertes & Eastman]. (shrink)

This book was originally published in 1981 and the theme of universals attracted a great deal of attention in the decade preceding publication.

The nonconsequentialist revival in tort theory has focused almost exclusively on one issue: showing that the rules governing compensation for acts reflect corrective justice rather than welfarist norms. The literature either is silent on what makes an act wrongful in the first place or suggests criteria that seem indistinguishable from some version of cost/benefit analysis. As a result, cost/benefit analysis is currently the only game in town for determining appropriate standards of conduct for socially useful but risky acts. This is (...) no small omission, and the failure of nonconsequentialists to acknowledge it or cure it can be traced to a number of recurring problems in the nonconsequentialist tort literature. Chief among them is the tendency to conflate prohibition and compensation, and to treat imposition of risk and imposition of harm as if they were distinct forms of conduct rather than the same conduct viewed from different temporal perspectives. (shrink)

In der 1970 gegründeten Reihe erscheinen Arbeiten, die philosophiehistorische Studien mit einem systematischen Ansatz oder systematische Studien mit philosophiehistorischen Rekonstruktionen verbinden. Neben deutschsprachigen werden auch englischsprachige Monographien veröffentlicht. Gründungsherausgeber sind: Erhard Scheibe (Herausgeber bis 1991), Günther Patzig (bis 1999) und Wolfgang Wieland (bis 2003). Von 1990 bis 2007 wurde die Reihe von Jürgen Mittelstraß mitherausgegeben.