The lymphatic vasculature plays a critical role in the regulation of body fluid volume and immune function. Extensive research into the molecular mechanisms that control blood vessel growth has led to identification of molecules that also regulate development and growth of the lymphatic vessels. This is generating a great deal of interest in the molecular control of the lymphatics in the context of embryogenesis, lymphatic disorders and tumor metastasis. Studies in animal models carried out over the past three years have (...) shown that the soluble protein growth factors, vascular endothelial growth factor (VEGF)‐C and VEGF‐D, and their cognate receptor tyrosine kinase, VEGF receptor‐3 (VEGFR‐3), are critical regulators of lymphangiogenesis. Furthermore, disfunction of VEGFR‐3 has recently been shown to cause lymphedema. The capacity to induce lymphangiogenesis by manipulation of the VEGF‐C/VEGF‐D/VEGFR‐3 signaling pathway offers new opportunities to understand the function of the lymphatic system and to develop novel treatments for lymphatic disorders. BioEssays 24:1030–1040, 2002. © 2002 Wiley‐Periodicals, Inc. (shrink)

In early 2013, the Indian government introduced new rules governing the conduct of clinical trials involving human participants. Among other provisions, the law requires that sponsors of research compensate participants who are injured during the course of their research participation. This article examines the effects of India's compensation law and the efforts that policymakers in India have made to tailor the law since its passage. I use the legal concept of acoustic separation as a framework to explain and justify the (...) approach that India has taken in refining its regulation of research related injuries. I conclude that India's example may provide useful lessons for research sponsors and lawmakers in other regulatory states seeking to promote a well-regulated biomedical research industry. (shrink)

The ethical recruitment of participants with neurological disorders in clinical research requires obtaining initial and ongoing informed consent. The purpose of this study is to characterize barriers faced by research personnel in obtaining informed consent from research participants with neurological disorders and to identify strategies applied by researchers to overcome those barriers. This study was designed as a web-based survey of US researchers with an optional follow-up interview. A subset of participants who completed the survey were selected using a stratified (...) purposeful sampling strategy and invited to participate in an in-depth qualitative interview by phone or video conference. Data were analyzed using a mixed methods approach, including content analysis of survey responses and thematic analysis of interview responses. Over 1 year, 113 survey responses were received from US research personnel directly involved in obtaining informed consent from participants in neurological research. Frequently identified barriers to informed consent included: cognitive and communication impairments (e.g. aphasia), unrealistic expectations of research participants, mistrust of medical research, time constraints, literacy barriers, lack of available social support, and practical or resource-related constraints. Strategies to enhance informed consent included: involving close others to support participant understanding of study-related information, collaborating with more experienced research personnel to facilitate training in obtaining informed consent, encouraging participants to review consent forms in advance of consent discussions, and using printed materials and visual references. Beyond conveying study-related information, researchers included in this study endorsed ethical responsibilities to support deliberation necessary to informed consent in the context of misconceptions about research, unrealistic expectations, limited understanding, mistrust, and/or pressure from close others. Findings highlight the importance of training researchers involved in obtaining informed consent in neurological research to address disease-specific challenges and to support the decision-making processes of potential research participants and their close others. (shrink)

Growth of the Hispanic consumer population in America is changing the marketplace landscape. Due to their considerable buying power, a better understanding of Hispanic consumer behavior has become a necessity. The marketing literature has examined issues regarding religiosity and attitude toward business in regards to consumer ethical beliefs as well as research differentiating consumers on the basis of ethnicity due to their inherently different religious principles. Therefore, the present study contributes to the existing consumer ethics literature by examining the roles (...) of religiosity and attitude toward business in determining consumer ethical beliefs. Furthermore, this study compares the relationships among religiosity, attitude toward business, and ethical beliefs at the sub-cultural level (i.e., between Hispanic and Anglo-American consumers). Survey data compare a sample of 187 predominately Catholic Hispanic consumers with a sample of 127 predominately protestant Anglo consumers. Results suggest a positive relationship between intrinsic religiousness and beliefs that questionable consumer activities are unethical. However, extrinsic religiousness does not impact consumer views as to the ethicality of consumer practices. Hispanics exhibit higher levels of extrinsic religiousness than Anglos, but no difference in terms of their intrinsic religiousness. Results also suggest that Hispanics have a more negative attitude toward business than Anglos do. Implications of these results are discussed. (shrink)

The process of dehumanization, or thinking of others as less than human, is a phenomenon with significant societal implications. According to Haslam's model, two concepts of humanness derive from comparing humans with either animals or machines: individuals may be dehumanized by likening them to either animals or machines, or humanized by emphasizing differences from animals or machines. Recent work in cognitive neuroscience emphasizes understanding cognitive processes in terms of interactions between distributed cortical networks. It has been found that reasoning about (...) internal mental states is associated with activation of the default mode network and deactivation of the task positive network ; whereas reasoning about mechanical processes produces the opposite pattern. We conducted two neuroimaging studies. The first examined the neural bases of dehumanization and its relation to these two brain networks, using images and voice-over social narratives which either implicitly contrasted or implicitly likened humans to either animals or machines. The second study addressed a discrepancy between findings from the first study and prior work on the neural correlates of dehumanization: using a design similar to prior work we examined neural responses to pictures of humans, animals and machines, presented without any social context. In both studies, human and humanizing conditions were associated with relatively high activity in the DMN and relatively low activity in the TPN. However, the non-human and dehumanizing conditions deviated in different ways: they demonstrated more marked changes either in the DMN or in the TPN. Notably, differences between the animal dehumanizing and humanizing conditions were most evident in regions associated with mechanistic reasoning, not in the mentalizing network. Conjunction analysis of contrasts from both paradigms revealed that only one region was consistently more active when participants saw human, a medial parietal region regarded as the central hub of the DMN. These findings provide a neural basis for Haslam's distinction between two types of dehumanization, and suggest that the DMN and TPN play opposing roles in creating a sense of moral concern. (shrink)

Dementia is a growing issue at the end of life that presents unique challenges for advance care planning. Advance directives are a useful and important component of end-of-life planning, but standard advance directives have less utility in cases of loss of capacity due to dementia. An advance directive designed to specifically address end-of-life issues in the setting of dementia can provide patients with increased autonomy and caregivers with improved information about the desires of the individual in question. The Dartmouth Dementia (...) Directive is a dementia-specific advance directive, available online, that seeks to address common concerns of individuals who are planning for dementia-related end-of-life care. This directive was piloted in a community-based workshop, which provided important details and perspective on the best use of dementia-specific advance directives in the greater population. (shrink)

Limited research has been done among pregnant people participating in investigational drug trials. To enhance the ethical understanding of pregnant people’s perspectives on research participation, we sought to describe motives and risk perceptions of participants in a phase 1 trial of ledipasvir/sofosbuvir treatment for chronic Hepatitis C virus during pregnancy. Pregnant people with chronic HCV infection enrolled in an open-label, phase 1 study of LDV/SOF participated in semi-structured, in-depth interviews to explore their reasons for participation and experiences within the study. (...) Pregnant people took 12 weeks of LDV/SOF and were interviewed at enrollment and at the end of study. We recorded the interviews, transcribed them verbatim, coded them using NVivo software, and performed inductive thematic analysis. Nine women completed the study yielding 18 interview transcripts. We identified two themes regarding motives and one regarding risk perception. Motives— Women conceptualized study participation as part of the caregiving role they associate with motherhood; participating was viewed as an act of caregiving for their infants, their families, themselves, and other pregnant women with chronic HCV. Women also noted that they faced multiple barriers to treatment prior to pregnancy that created a desire to receive therapy through trial participation. Risk perception— Women acknowledged personal and fetal risk associated with participation. Acceptance of risk was influenced by women’s concepts of motherhood, preexisting knowledge of HCV and medical research, family members, intimate partners, or by the study design. Women enrolled in a phase 1 trial for chronic HCV therapy during pregnancy acknowledged risks of participation and were motivated by hopes for fetal and personal benefit and by lack of prenatal access to treatment. Ethical inclusion of pregnant people in research should acknowledge structural factors that contribute to vulnerability and data deficiencies for treatment in pregnancy. (shrink)

Research on escalation of commitment has predominantly been studied in the context of a single decision without consideration for the psychological consequences of escalating. This study sought to examine a) the extent to which people escalate their commitment to a failing course of action in a sequential decision-making task, b) confidence and anger as psychological consequences of escalation of commitment, and c) the reciprocal relationship between escalation of commitment and confidence and anger. Participants were 110 undergraduate students who completed a (...) series of investment decisions regarding a failing endeavor. Results revealed that although a high proportion of individuals escalate through all decisions, the extent to which they escalated decreased with each decision as they were less willing to invest money in the project. Furthermore, as participants escalated, confidence in one’s decision decreased and anger increased. Lastly, the analyses revealed that the relationship between escalation and confidence is reciprocal. Escalation was negatively associated with confidence, and confidence predicted escalation in the subsequent decision. These results highlight the importance of considering both the determinants and psychological consequences of escalation of commitment. (shrink)

In this target article by Morain and Largent (2023), the authors focus on an investigator’s duty to patient-subjects specifically regarding incidental or collateral findings within the context of e...

Despite the growing body of literature on training in the responsible conduct of research, few studies have examined the effectiveness of delivery formats used in ethics courses. The present effort sought to address this gap in the literature through a meta-analytic review of 66 empirical studies, representing 106 ethics courses and 10,069 participants. The frequency and effectiveness of 67 instructional and process-based content areas were also assessed for each delivery format. Process-based contents were best delivered face-to-face, whereas contents delivered online (...) were most effective when restricted to compliance-based instructional contents. Overall, hybrid courses were found to be most effective, suggesting that ethics courses are best delivered using a blend of formats and content areas. Implications and recommendations for future development of ethics education courses in the sciences are discussed. (shrink)

Events—the experiences we think we are having and recall having had—are constructed; they are not what actually occurs. What occurs is ongoing dynamic, multidimensional, sensory flow, which is somehow transformed via psychological processes into structured, describable, memorable units of experience. But what is the nature of the redescription processes that fluently render dynamic sensory streams as event representations? How do such processes cope with the ubiquitous novelty and variability that characterize sensory experience? How are event‐rendering skills acquired and how do (...) event representations change with development? This review considers emerging answers to these questions, beginning with evidence that an implicit tendency to monitor predictability structure via statistical learning is key to event rendering. That is, one way that the experience of bounded events (e.g., actions within behavior, words within speech) arises is with the detection of “troughs” in sensory predictability. Interestingly, such troughs in predictability are often predictable; these regions of predictable‐unpredictability provide articulation points to demarcate one event from another in representations derived from the actual streaming information. In our information‐optimization account, a fluent event‐processor predicts such troughs and selectively attends to them—while suppressing attention to other regions—as sensory streams unfold. In this way, usage of attentional resources is optimized for efficient sampling of the most relevant, information‐rich portions of the unfolding flow of sensation. Such findings point to the development of event‐processing fluency—whether in action, language, or other domains—depending crucially on rapid and continual cognitive reorganization. As knowledge of predictability grows, attention is adaptively redeployed. Accordingly, event experiences undergo continuous alteration. (shrink)

In their target article, Conley et al. (2023) appropriately highlight the ongoing conceptual and practical opacity of public engagement (PE) in the translation of human gene editing (HGE) (Conley e...

Ethics courses are most commonly evaluated using reaction measures. However, little is known about the specific types of reaction data being collected and how these reaction data relate to improvements in trainee performance. Using a sample of 381 ethics training sessions, major reaction data categories were identified. Content and course satisfaction were the most frequently collected types of reaction criteria. Furthermore, content relevance and course satisfaction showed strong, positive relationships with performance criteria, whereas content satisfaction demonstrated a moderate, negative relationship. (...) These results and future directions for ethics training evaluation are discussed. (shrink)

In our article, we share the lessons we have learned after creating and running a successful legal laboratory over the past seven years at Yale Law School. Our legal laboratory, which focuses on the intersection of law and severe brain injury, represents a unique pedagogical model for legal academia, and is closely influenced by the biomedical laboratory.

As the technology for ectogenesis continues to advance, the ethical implications of such developments should be thoroughly and proactively explored. The possibility of full ectogenesis remains hypothetical at present, and myriad concerns regarding the safety and efficacy of the technology must be evaluated and addressed, while pressing moral considerations should be fully deliberated. However, it is conceivable that the technology may become sufficiently well established in the future and that eventually full ectogenesis might be deemed ethically acceptable as a reproductive (...) alternative to gestation within a human womb under certain circumstances. If the safety and efficacy of full ectogenesis are established, if ethical dilemmas are sufficiently well addressed, and if the technology is offered as a reproductive option to cisgender heterosexual individuals or couples desiring to become parents, there is a moral obligation grounded in social justice to ensure that full ectogenesis be made available to individuals or couples identifying as members of sexual‐ or gender‐minority groups who likewise seek to pursue parenthood. We examine the history of access to current family‐building options, including assisted reproductive technology, surrogacy and adoption, for these populations and conclude that in the absence of robust empirical evidence suggesting an increased risk of harm to children of individuals and couples who identify as members of sexual‐ or gender‐minority groups, equitable access to ectogenesis as a pathway to parenthood for sexual and gender minorities must be assured as a matter of reproductive justice. (shrink)

The literature on affective determinants of physical activity is growing rapidly. The present paper aims to provide greater clarity regarding the definition and distinctions among the various affect-related constructs that have been examined in relation to PA. Affective constructs are organized according to the Affect and Health Behavior Framework, including: affective response to PA; incidental affect; affect processing; and affectively charged motivational states. After defining each category of affective construct, we provide examples of relevant research showing how each construct may (...) relate to PA behavior. We conclude each section with a discussion of future directions for research. (shrink)

This book is available either individually, or as part of the specially-priced Arguments of the Philosphers Collection.

No names are more closely associated with modern trade theory than Eli Heckscher and Bertil Ohlin. The basic Heckscher-Ohlin proposition, according to which a country exports factors in abundant supply and imports factors in scarce supply, is a key component of modern trade theory. In this book, Robert Baldwin traces the development of the HO model, describing the historical twists and turns that have led to the basic modern theoretical model in use today. Baldwin not only presents a (...) clear and cohesive view of the model's evolution but also reviews the results of empirical tests its various versions. Baldwin, who published his first theoretical article on the HO model in 1948, first surveys the development of the HO model and then assesses empirical tests of its predictions. Most discussions of empirical work on HO models confine themselves to the basic theorem, but Baldwin devotes a chapter to empirical tests of three related propositions: the Stolper-Samuelson theorem; the Rybczynski theorem; and the factor price equalization theorem. He concludes that the formulation and testing of these later models have improved economists' understanding of the forces shaping international trade, but that many empirical trade economists were so enamored of the elegant but highly unrealistic factor price equalization models developed from the insights of Heckscher and Ohlin that they have neglected investigation of other models without this relationship. (shrink)

There is limited knowledge about cancer patients' experiences of uncertainty while waiting for genome sequencing results, and whether prolonged uncertainty contributes to psychological factors in this context. To investigate uncertainty in patients with a cancer of likely hereditary origin while waiting for genome sequencing results, we collected questionnaire and interview data at baseline, and at three and 12 months follow up. Participants had negative attitudes towards uncertainty at baseline, and low levels of uncertainty at three and 12 months. Uncertainty about (...) genome sequencing did not change significantly over time [t = 0.660, p = 0.510]. Greater perceived susceptibility for cancer [r = 0.14, p < 0.01], fear of cancer recurrence [r = 0.19, p < 0.01], perceived importance of genome sequencing [r = 0.24, p < 0.01], intention to change behavior if a gene variant indicating risk is found [r = 0.29, p < 0.01], perceived ability to cope with results [r = 0.36, p < 0.01], and satisfaction with decision to have genome sequencing [r = 0.52, p < 0.01] were significantly correlated with negative attitudes towards uncertainty at baseline. Multiple primary cancer diagnoses [B = −2.364 [−4.238, −0.491], p = 0.014], lower perceived ability to cope with results [B = −0.1.881 [−3.403, −0.359], p = 0.016] at baseline, greater anxiety about genome sequencing [B = 0.347 [0.148, 0.546], p = 0.0012] at 3 months, and greater perceived uncertainty about genome sequencing [B = 0.494 [0.267, 0.721] p = 0.000] at 3 months significantly predicted greater perceived uncertainty about genome sequencing at 12 months. Greater perceived uncertainty about genome sequencing at 3 months significantly predicted greater anxiety about genome sequencing at 12 months [B = 0.291 [0.072, 0.509], p = 0.009]. Semi-structured interviews revealed that while participants were motivated to pursue genome sequencing as a strategy to reduce their illness and risk uncertainty, genome sequencing generated additional practical, scientific and personal uncertainties. Some uncertainties were consistently discussed over the 12 months, while others emerged over time. Similarly, some uncertainty coping strategies were consistent over time, while others emerged while patients waited for their genome sequencing results. This study demonstrates the complexity of uncertainty generated by genome sequencing for cancer patients and provides further support for the inter-relationship between uncertainty and anxiety. Helping patients manage their uncertainty may ameliorate psychological morbidity. (shrink)

This article systematically reviews studies investigating the effect of three operationalizations of complexity in emotion experience on situat...

G.E. Moore, more than either Bertrand Russell or Ludwig Wittgenstein, was chiefly responsible for the rise of the analytic method in twentieth-century philosophy. This selection of his writings shows Moore at his very best. The classic essays are crucial to major philosophical debates that still resonate today. Amongst those included are: * _A Defense of Common Sense * Certainty * Sense-Data * External and Internal Relations * Hume's Theory Explained * Is Existence a Predicate? * Proof of an External World (...) In addition, this collection also contains the key early papers in which Moore signals his break with idealism, and three important previously unpublished papers from his later work which illustrate his relationship with Wittgenstein._. (shrink)

College students from small, medium, and large institutions with either a modified or no honor code were presented with cheating scenarios and asked to rate how dishonest they perceived the behavior to be and the likelihood that they would report it. No main effects were found for institution size or type of honor code. Student–faculty ratio was not correlated with responses to the cheating scenarios. Students from modified honor code schools perceived more severe punishments for cheating and understood the reporting (...) process better than students from non–honor code schools. Implications for modified honor code systems are discussed. (shrink)

Philosophers analyze the last of the great rock stars.

ABSTRACTAnxiety and depression diagnoses are associated with suicidal thoughts and behaviours. However, a categorical understanding of these associations limits insight into identifying dimensional mechanisms of suicide risk. This study investigated anxious and depressive features through a lens of suicide risk, independent of diagnosis. Latent class analysis of 97 depression, anxiety, and suicidality-related items among 616 psychiatric outpatients indicated a 3-class solution, specifically: a higher suicide-risk class uniquely differentiated from both other classes by high reported levels of depression and anxious arousal; (...) a lower suicide-risk class that reported levels of anxiety sensitivity and generalised worry comparable to Class 1, but lower levels of depression and anxious arousal; and a low to non-suicidal class that reported relatively low levels across all depression and anxiety measures. Discriminants of the higher suicide-risk class included borderline personality disorder; report... (shrink)